Difference between revisions of "Venous thromboembolism"
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− | + | <div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px"> | |
− | + | [[#top|Back to Top]] | |
− | + | </div> | |
− | + | {{#lst:Editorial board transclusions|heme}} | |
− | + | ''Are you looking for a regimen, but can't find it here? For placebo or observational studies in this condition, please visit [[Venous thromboembolism - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''<br> | |
− | + | Note that there is a considerable literature on using these agents in the prevention of thromboembolism associated with atrial fibrillation and mechanical heart valves. As these conditions are out of the purview of HemOnc.org, this page primarily focuses on the prevention and treatment of venous thromboembolism (VTE). | |
− | + | *''We have moved [[How I Treat]] articles to a dedicated page.'' | |
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<br>'''Other pages on HemOnc.org regarding management of deep vein thrombosis (DVT) and pulmonary embolism (PE) include:''' | <br>'''Other pages on HemOnc.org regarding management of deep vein thrombosis (DVT) and pulmonary embolism (PE) include:''' | ||
*[[Bleeding with anticoagulation]] | *[[Bleeding with anticoagulation]] | ||
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*[[Hypercoagulable state (thrombophilia)]] evaluation | *[[Hypercoagulable state (thrombophilia)]] evaluation | ||
*[[Compression stockings and sleeves]] for management and prophylaxis against postphlebitic (postthrombotic) syndrome<ref>[http://circ.ahajournals.org/content/121/8/e217.full Circulation patient page about postthrombotic syndrome (PTS)]</ref> | *[[Compression stockings and sleeves]] for management and prophylaxis against postphlebitic (postthrombotic) syndrome<ref>[http://circ.ahajournals.org/content/121/8/e217.full Circulation patient page about postthrombotic syndrome (PTS)]</ref> | ||
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{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
+ | =Living Interactive Systematic Reviews= | ||
+ | *[https://cat.network-meta-analysis.com/ Direct oral anti-coagulants compared to dalteparin] | ||
=Guidelines= | =Guidelines= | ||
+ | '''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.''' | ||
==ACCP== | ==ACCP== | ||
− | *'''2012:''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278049/ Antithrombotic Therapy for VTE Disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines] | + | *'''2012:''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278049/ Antithrombotic Therapy for VTE Disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines] [https://pubmed.ncbi.nlm.nih.gov/22315268/ PubMed] |
==[https://www.asco.org/ ASCO]== | ==[https://www.asco.org/ ASCO]== | ||
− | *''' | + | *'''2023:''' Key et al. [https://doi.org/10.1200/jco.23.00294 Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Guideline Update] [https://pubmed.ncbi.nlm.nih.gov/37075273/ PubMed] |
− | |||
− | + | *'''2019:''' Key et al. [https://doi.org/10.1200/JCO.19.01461 Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update.] [https://pubmed.ncbi.nlm.nih.gov/31381464/ PubMed] | |
− | *''' | + | *'''2015:''' Lyman et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881372/ ASCO Clinical Practice Guideline on VTE prophylaxis and treatment 2014 update] [https://pubmed.ncbi.nlm.nih.gov/25605844/ PubMed] |
+ | *'''2013:''' Lyman et al. [https://doi.org/10.1200/JCO.2013.49.1118 Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update] [https://pubmed.ncbi.nlm.nih.gov/23669224/ PubMed] | ||
+ | *'''2007:''' Lyman et al. [https://doi.org/10.1200/JCO.2007.14.1283 American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer.] [https://pubmed.ncbi.nlm.nih.gov/17968019/ PubMed] | ||
==[https://www.hematology.org/ ASH]== | ==[https://www.hematology.org/ ASH]== | ||
− | *''' | + | *'''2021:''' Lyman et al. [https://doi.org/10.1182/bloodadvances.2020003442 American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903232/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33570602/ PubMed] |
− | *'''2018:''' Lim et al. [ | + | *'''2020:''' Ortel et al. [https://doi.org/10.1182/bloodadvances.2020001830 American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556153/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33007077/ PubMed] |
− | *'''2018:''' Witt et al. [ | + | *'''2019:''' Anderson et al. [https://doi.org/10.1182/bloodadvances.2019000975 American Society of Hematology 2019 guidelines for management of venous thromboembolism: prevention of venous thromboembolism in surgical hospitalized patients] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963238/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31794602/ PubMed] |
− | *'''2018:''' Monagle et al. [ | + | *'''2018:''' Schünemann et al. [https://doi.org/10.1182/bloodadvances.2018022954 American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258910/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30482763/ PubMed] |
− | *'''2018:''' Bates et al. [ | + | *'''2018:''' Lim et al. [https://doi.org/10.1182/bloodadvances.2018024893 American Society of Hematology 2018 guidelines for management of venous thromboembolism: diagnosis of venous thromboembolism] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258916/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30482764/ PubMed] |
− | *'''2018:''' Cuker et al. [ | + | *'''2018:''' Witt et al. [https://doi.org/10.1182/bloodadvances.2018024893 American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258922/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30482765/ PubMed] |
+ | *'''2018:''' Monagle et al. [https://doi.org/10.1182/bloodadvances.2018024786 American Society of Hematology 2018 Guidelines for management of venous thromboembolism: treatment of pediatric venous thromboembolism] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258911/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30482766/ PubMed] | ||
+ | *'''2018:''' Bates et al. [https://doi.org/10.1182/bloodadvances.2018024802 American Society of Hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258928/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30482767/ PubMed] | ||
+ | *'''2018:''' Cuker et al. [https://doi.org/10.1182/bloodadvances.2018024489 American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258919/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30482768/ PubMed] | ||
− | ==[ | + | ==[https://www.esmo.org/ ESMO]== |
− | *'''2010:''' [ | + | *'''2023:''' Falanga et al. [https://doi.org/10.1016/j.annonc.2022.12.014 Venous thromboembolism in cancer patients: ESMO Clinical Practice Guideline] [https://pubmed.ncbi.nlm.nih.gov/36638869/ PubMed] |
+ | **'''2010:''' Mandalà et al. [https://doi.org/10.1016/s0049-3848(10)70028-1 Venous thromboembolism (VTE) in cancer patients. ESMO clinical recommendations for prevention and management] [https://pubmed.ncbi.nlm.nih.gov/20433989/ PubMed] | ||
+ | **'''2009:''' Mandalà et al. [https://doi.org/10.1093/annonc/mdp167 Management of venous thromboembolism in cancer patients: ESMO clinical recommendations] [https://pubmed.ncbi.nlm.nih.gov/19454449/ PubMed] | ||
==IMWG== | ==IMWG== | ||
===Current=== | ===Current=== | ||
− | * | + | *[https://www.myeloma.org/resource-library/imwg-guidelines-prevention-thalidomide-lenalidomide-associated-thrombosis-myeloma IMWG guidelines for the prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma] [https://pubmed.ncbi.nlm.nih.gov/18094721/ PubMed] |
+ | |||
+ | |||
+ | *'''2007:''' [https://doi.org/10.1038/sj.leu.2405062 Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma] [https://pubmed.ncbi.nlm.nih.gov/18094721/ PubMed] | ||
+ | ==ITAC (International Initiative on Thrombosis and Cancer)== | ||
+ | *'''2022:''' Farge et al. [https://doi.org/10.1016/S1470-2045(22)00160-7 2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9236567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35772465/ PubMed] | ||
− | + | *'''2019:''' Farge et al. [https://doi.org/10.1016/s1470-2045(19)30336-5 2019 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer] [https://pubmed.ncbi.nlm.nih.gov/31492632/ PubMed] | |
− | *''' | + | *'''2016:''' Farge et al. [https://doi.org/10.1016/S1470-2045(16)30369-2 International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer] [https://pubmed.ncbi.nlm.nih.gov/27733271/ PubMed] |
+ | *'''2013:''' Farge et al. [https://doi.org/10.1111/jth.12070 International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer] [https://pubmed.ncbi.nlm.nih.gov/23217107/ PubMed] | ||
− | == | + | ==NCCN== |
− | *''' | + | *[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1423 NCCN Guidelines - Cancer-Associated Venous Thromboembolic Disease] |
+ | **'''2015:''' Streiff et al. [https://doi.org/10.6004/jnccn.2015.0133 Cancer-Associated Venous Thromboembolic Disease, Version 1.2015] [https://pubmed.ncbi.nlm.nih.gov/26358792/ PubMed] | ||
+ | **'''2013:''' Streiff et al. [https://doi.org/10.6004/Jnccn.2013.0163 Venous thromboembolic disease.] [https://pubmed.ncbi.nlm.nih.gov/24225973/ PubMed] | ||
+ | **'''2011:''' Streiff et al. [https://doi.org/10.6004/Jnccn.2011.0062 Venous thromboembolic disease.] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551573/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21715723/ PubMed] | ||
+ | **'''2008:''' Wagman et al. [https://doi.org/10.6004/Jnccn.2008.0055 Venous thromboembolic disease. NCCN. Clinical practice guidelines in oncology.] [https://pubmed.ncbi.nlm.nih.gov/18926086/ PubMed] | ||
+ | **'''2006:''' Wagman et al. [https://doi.org/10.6004/Jnccn.2006.0071 Venous thromboembolic disease. Clinical practice guidelines in oncology.] [https://pubmed.ncbi.nlm.nih.gov/17020664/ PubMed] | ||
=VTE primary prophylaxis= | =VTE primary prophylaxis= | ||
==Apixaban monotherapy {{#subobject:9958a4|Regimen=1}}== | ==Apixaban monotherapy {{#subobject:9958a4|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #1, 10-14 days post-op {{#subobject:734aaa|Variant=1}}=== | |
− | |||
− | |||
− | === | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
|<small>'''FDA-recommended dose'''</small> | |<small>'''FDA-recommended dose'''</small> | ||
|- | |- | ||
|} | |} | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 17%"|Study |
− | !style="width: | + | !style="width: 15%"|Dates of enrollment |
− | !style="width: | + | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: | + | !style="width: 17%"|Comparator |
− | !style="width: | + | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa0810773 Lassen et al. 2009 (ADVANCE-1)]] |
− | | style="background-color:#1a9851" |Phase | + | |Not reported |
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
|[[#Enoxaparin_monotherapy|Enoxaparin]] | |[[#Enoxaparin_monotherapy|Enoxaparin]] | ||
− | | style="background-color:#ffffbf" | | + | | style="background-color:#ffffbf" |Inconclusive whether non-inferior asymptomatic and symptomatic DVT, nonfatal PE, and death from any cause during treatment (primary endpoint) |
| style="background-color:#91cf60" |Seems to have lower bleeding rate | | style="background-color:#91cf60" |Seems to have lower bleeding rate | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(09)62125-5 Lassen et al. 2010 (ADVANCE-2)] |
− | | style="background-color:#1a9851" |Phase | + | |2007-06-29 to 2008-11-12 |
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
|[[#Enoxaparin_monotherapy|Enoxaparin]] | |[[#Enoxaparin_monotherapy|Enoxaparin]] | ||
− | | style="background-color:#1a9850" |Superior composite endpoint | + | | style="background-color:#1a9850" |Superior composite primary endpoint |
| style="background-color:#d9ef8b" |Might have lower bleeding rate | | style="background-color:#d9ef8b" |Might have lower bleeding rate | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
*Total knee replacement | *Total knee replacement | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
− | *[[Apixaban (Eliquis)]] 2.5 mg PO twice per day, beginning 12 to 24 h after wound closure | + | *[[Apixaban (Eliquis)]] 2.5 mg PO twice per day, beginning 12 to 24 h after wound closure |
− | |||
'''10- to 14-day course''' | '''10- to 14-day course''' | ||
− | + | </div></div><br> | |
− | === | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #2, 35 days post-op {{#subobject:15ab8c|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
|<small>'''FDA-recommended dose'''</small> | |<small>'''FDA-recommended dose'''</small> | ||
|- | |- | ||
|} | |} | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 17%"|Study |
− | !style="width: | + | !style="width: 15%"|Dates of enrollment |
− | !style="width: | + | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: | + | !style="width: 17%"|Comparator |
− | !style="width: | + | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1006885 Lassen et al. 2010 (ADVANCE-3)] |
− | | style="background-color:#1a9851" |Phase | + | |2007-03 to 2009-05 |
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
|[[#Enoxaparin_monotherapy|Enoxaparin]] | |[[#Enoxaparin_monotherapy|Enoxaparin]] | ||
− | | style="background-color:#1a9850" |Superior composite endpoint | + | | style="background-color:#1a9850" |Superior composite primary endpoint |
− | | style="background-color:#ffffbf" | | + | | style="background-color:#ffffbf" |Did not meet endpoint of major and clinically relevant nonmajor bleeding |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
*Total hip replacement | *Total hip replacement | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
− | *[[Apixaban (Eliquis)]] 2.5 mg PO twice per day, beginning 12 to 24 h after wound closure | + | *[[Apixaban (Eliquis)]] 2.5 mg PO twice per day, beginning 12 to 24 h after wound closure |
− | |||
'''35-day course''' | '''35-day course''' | ||
− | + | </div></div><br> | |
− | === | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #3, 180 days {{#subobject:15cd2c|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
|<small>'''FDA-recommended dose'''</small> | |<small>'''FDA-recommended dose'''</small> | ||
|- | |- | ||
|} | |} | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 17%"|Study |
− | !style="width: | + | !style="width: 15%"|Dates of enrollment |
− | !style="width: | + | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: | + | !style="width: 17%"|Comparator |
− | !style="width: | + | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1814468 Carrier et al. 2018 (AVERT)] |
− | | style="background-color:#1a9851" |Phase | + | |2014-02 to 2018-04 |
− | |[[#Placebo|Placebo]] | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | | style="background-color:#1a9850" |Superior VTE rate | + | |[[Venous_thromboembolism_-_null_regimens#Placebo|Placebo]] |
+ | | style="background-color:#1a9850" |Superior VTE rate over 180 days (primary endpoint) | ||
| style="background-color:#fc8d59" |Seems to have higher rate of bleeding | | style="background-color:#fc8d59" |Seems to have higher rate of bleeding | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
− | *[[Apixaban (Eliquis)]] 2.5 mg PO twice per day, beginning within 24 h of initiation of chemotherapy | + | *[[Apixaban (Eliquis)]] 2.5 mg PO twice per day, beginning within 24 h of initiation of chemotherapy |
− | |||
'''6-month course''' | '''6-month course''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''ADVANCE-1:''' Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Portman RJ. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med. 2009 Aug 6;361(6):594-604. Erratum in: N Engl J Med. 2009 Oct 29;361(18):1814. [https:// | + | #'''ADVANCE-1:''' Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Portman RJ. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med. 2009 Aug 6;361(6):594-604. Erratum in: N Engl J Med. 2009 Oct 29;361(18):1814. [https://doi.org/10.1056/NEJMoa0810773 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19657123/ PubMed] [https://clinicaltrials.gov/study/NCT00371683 NCT00371683] |
− | # '''ADVANCE-2:''' Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P; ADVANCE-2 investigators. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet. 2010 Mar 6;375(9717):807-15. [https:// | + | #'''ADVANCE-2:''' Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P; ADVANCE-2 investigators. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet. 2010 Mar 6;375(9717):807-15. [https://doi.org/10.1016/S0140-6736(09)62125-5 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20206776/ PubMed] [https://clinicaltrials.gov/study/NCT00452530 NCT00452530] |
− | # '''ADVANCE-3:''' Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM; ADVANCE-3 Investigators. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med. 2010 Dec 23;363(26):2487-98. [https:// | + | #'''ADVANCE-3:''' Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM; ADVANCE-3 Investigators. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med. 2010 Dec 23;363(26):2487-98. [https://doi.org/10.1056/NEJMoa1006885 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21175312/ PubMed] [https://clinicaltrials.gov/study/NCT00423319 NCT00423319] |
− | # '''AVERT:''' Carrier M, Abou-Nassar K, Mallick R, Tagalakis V, Shivakumar S, Schattner A, Kuruvilla P, Hill D, Spadafora S, Marquis K, Trinkaus M, Tomiak A, Lee AYY, Gross PL, Lazo-Langner A, El-Maraghi R, Goss G, Le Gal G, Stewart D, Ramsay T, Rodger M, Witham D, Wells PS; AVERT Investigators. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med. 2019 Feb 21;380(8):711-719. Epub 2018 Dec 4. [https:// | + | #'''AVERT:''' Carrier M, Abou-Nassar K, Mallick R, Tagalakis V, Shivakumar S, Schattner A, Kuruvilla P, Hill D, Spadafora S, Marquis K, Trinkaus M, Tomiak A, Lee AYY, Gross PL, Lazo-Langner A, El-Maraghi R, Goss G, Le Gal G, Stewart D, Ramsay T, Rodger M, Witham D, Wells PS; AVERT Investigators. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med. 2019 Feb 21;380(8):711-719. Epub 2018 Dec 4. [https://doi.org/10.1056/NEJMoa1814468 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/30511879/ PubMed] [https://clinicaltrials.gov/study/NCT02048865 NCT02048865] |
+ | #'''PREVAPIX-ALL:''' O'Brien SH, Rodriguez V, Lew G, Newburger JW, Schultz CL, Orgel E, Derr K, Ranalli MA, Esbenshade AJ, Hochberg J, Kang HJ, Dinikina Y, Mills D, Donovan M, Dyme JL, Favatella NA, Mitchell LG; PREVAPIX-ALL investigators. Apixaban versus no anticoagulation for the prevention of venous thromboembolism in children with newly diagnosed acute lymphoblastic leukaemia or lymphoma (PREVAPIX-ALL): a phase 3, open-label, randomised, controlled trial. Lancet Haematol. 2024 Jan;11(1):e27-e37. Epub 2023 Nov 16. [https://doi.org/10.1016/s2352-3026(23)00314-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37980924/ PubMed] [https://clinicaltrials.gov/study/NCT02369653 NCT02369653] | ||
==Aspirin monotherapy {{#subobject:2b1389|Regimen=1}}== | ==Aspirin monotherapy {{#subobject:2b1389|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:e721b6|Variant=1}}=== | ===Regimen {{#subobject:e721b6|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | ! style="width: | + | !style="width: 20%"|Study |
− | ! style="width: | + | !style="width: 20%"|Dates of enrollment |
− | ! style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ! style="width: | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(00)02110-3 Rodgers et al. 2000 (PEP)] |
− | | style="background-color:#1a9851" |Phase | + | |1992-1998 |
− | |Placebo | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
+ | |[[Venous_thromboembolism_-_null_regimens#Placebo|Placebo]] | ||
| style="background-color:#1a9850" |Superior VTE rate | | style="background-color:#1a9850" |Superior VTE rate | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/nejmoa035572 Landolfi et al. 2004 (ECLAP)] |
− | | style="background-color:#1a9851" |Phase | + | |Not reported |
− | |Placebo | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | | style="background-color:#91cf60" |Seems to have superior rate of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes | + | |[[Venous_thromboembolism_-_null_regimens#Placebo|Placebo]] |
+ | | style="background-color:#91cf60" |Seems to have superior rate of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes (primary endpoint) | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1200/JCO.2010.31.6844 Palumbo et al. 2011 (GIMEMA MM-03-05)] |
− | | style="background-color:#1a9851" |Phase | + | |2006-05 to 2009-01 |
− | |1. [[#Enoxaparin_monotherapy|Enoxaparin]]<br> 2. | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
− | | style="background-color:#ffffbf" | | + | |1. [[#Enoxaparin_monotherapy|Enoxaparin]]<br>2. [[#Warfarin_monotherapy_888|Warfarin]]; low-dose |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of serious thromboembolic events, acute cardiovascular events, or sudden deaths during the first 6 months of treatment | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2011-03-344333 Larocca et al. 2011 (MPRvsMEL200<sub>VTE</sub>)] |
− | | style="background-color:#1a9851" |Phase | + | |2007-11 to 2009-06 |
+ | | style="background-color:#1a9851" |Phase 3 (E-de-esc) | ||
|[[#Enoxaparin_monotherapy|Enoxaparin]] | |[[#Enoxaparin_monotherapy|Enoxaparin]] | ||
− | | style="background-color:#ffffbf" | | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of VTE incidence |
|- | |- | ||
− | |[ | + | |[https://doi.org/10.7326/0003-4819-158-11-201306040-00004 Anderson et al. 2013 (EPCAT)] |
− | | style="background-color:#1a9851" |Phase | + | |2007-2010 |
− | |Dalteparin | + | | style="background-color:#1a9851" |Phase 3 (E-de-esc) |
− | | style="background-color:#eeee01" |Non-inferior VTE rate at 90 days | + | |[[#Dalteparin_monotherapy_888|Dalteparin]] |
+ | | style="background-color:#eeee01" |Non-inferior VTE rate at 90 days (primary endpoint) | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1712746 Anderson et al. 2018 (EPCAT II)] |
− | | style="background-color:#1a9851" |Phase | + | |2013-01 to 2016-04 |
+ | | style="background-color:#1a9851" |Phase 3 (E-de-esc) | ||
|[[#Rivaroxaban_monotherapy|Rivaroxaban]] | |[[#Rivaroxaban_monotherapy|Rivaroxaban]] | ||
− | | style="background-color:#eeee01" |Non-inferior VTE rate at 90 days | + | | style="background-color:#eeee01" |Non-inferior VTE rate at 90 days (primary endpoint) |
+ | |- | ||
+ | |[https://doi.org/10.1056/NEJMoa2205973 O'Toole et al. 2023 (PREVENT CLOT)] | ||
+ | |2017-04 to 2021-08 | ||
+ | | style="background-color:#1a9851" |Randomized (C) | ||
+ | |[[#Enoxaparin_monotherapy|Enoxaparin]] | ||
+ | | style="background-color:#eeee01" |Non-inferior death rate at 90 days | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: Palumbo et al. 2011 was a substudy looking at thromboprophylaxis in the thalidomide arm. Larocca et al. 2011 was also a substudy looking at thromboprophylaxis in the lenalidomide arm.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
*[[Aspirin]] 81 to 160 mg PO once per day | *[[Aspirin]] 81 to 160 mg PO once per day | ||
− | |||
'''Various durations, see individual trials''' | '''Various durations, see individual trials''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''PEP:''' Rodgers A, MacMahon S, Collins R, Prentice C; Pulmonary Embolism Prevention (PEP) trial Collaborative Group. Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial. Lancet. 2000 Apr 15;355(9212):1295-302. [https:// | + | #'''PEP:''' Rodgers A, MacMahon S, Collins R, Prentice C; Pulmonary Embolism Prevention (PEP) trial Collaborative Group. Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial. Lancet. 2000 Apr 15;355(9212):1295-302. [https://doi.org/10.1016/S0140-6736(00)02110-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10776741/ PubMed] |
− | # '''ECLAP:''' Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, Barbui T; European Collaboration on Low-Dose Aspirin in Polycythemia Vera Investigators. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004 Jan 8;350(2):114-24. [https:// | + | #'''ECLAP:''' Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, Barbui T; European Collaboration on Low-Dose Aspirin in Polycythemia Vera Investigators. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004 Jan 8;350(2):114-24. [https://doi.org/10.1056/nejmoa035572 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14711910/ PubMed] |
− | # Palumbo A, Cavo M, Bringhen S, Zamagni E, Romano A, Patriarca F, Rossi D, Gentilini F, Crippa C, Galli M, Nozzoli C, Ria R, Marasca R, Montefusco V, Baldini L, Elice F, Callea V, Pulini S, Carella AM, Zambello R, Benevolo G, Magarotto V, Tacchetti P, Pescosta N, Cellini C, Polloni C, Evangelista A, Caravita T, Morabito F, Offidani M, Tosi P, Boccadoro M. Aspirin, warfarin, or enoxaparin thromboprophylaxis in patients with multiple myeloma treated with thalidomide: a phase III, open-label, randomized trial. J Clin Oncol. 2011 Mar 10;29(8):986-93. Epub 2011 Jan 31. [https:// | + | # '''GIMEMA MM-03-05:''' Palumbo A, Bringhen S, Rossi D, Cavalli M, Larocca A, Ria R, Offidani M, Patriarca F, Nozzoli C, Guglielmelli T, Benevolo G, Callea V, Baldini L, Morabito F, Grasso M, Leonardi G, Rizzo M, Falcone AP, Gottardi D, Montefusco V, Musto P, Petrucci MT, Ciccone G, Boccadoro M. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial. J Clin Oncol. 2010 Dec 1;28(34):5101-9. Epub 2010 Oct 12. [https://doi.org/10.1200/jco.2010.29.8216 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20940200/ PubMed] [https://clinicaltrials.gov/study/NCT01063179 NCT01063179] |
− | # Larocca A, Cavallo F, Bringhen S, Di Raimondo F, Falanga A, Evangelista A, Cavalli M, Stanevsky A, Corradini P, Pezzatti S, Patriarca F, Cavo M, Peccatori J, Catalano L, Carella AM, Cafro AM, Siniscalchi A, Crippa C, Petrucci MT, Yehuda DB, Beggiato E, Di Toritto TC, Boccadoro M, Nagler A, Palumbo A. Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide. Blood. 2012 Jan 26;119(4):933-9. Epub 2011 Aug 11. [ | + | ## '''Post-hoc analysis:''' Bringhen S, Larocca A, Rossi D, Cavalli M, Genuardi M, Ria R, Gentili S, Patriarca F, Nozzoli C, Levi A, Guglielmelli T, Benevolo G, Callea V, Rizzo V, Cangialosi C, Musto P, De Rosa L, Liberati AM, Grasso M, Falcone AP, Evangelista A, Cavo M, Gaidano G, Boccadoro M, Palumbo A. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood. 2010 Dec 2;116(23):4745-53. Epub 2010 Aug 31. [https://doi.org/10.1182/blood-2010-07-294983 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20807892/ PubMed] |
− | # '''EPCAT:''' Anderson DR, Dunbar MJ, Bohm ER, Belzile E, Kahn SR, Zukor D, Fisher W, Gofton W, Gross P, Pelet S, Crowther M, MacDonald S, Kim P, Pleasance S, Davis N, Andreou P, Wells P, Kovacs M, Rodger MA, Ramsay T, Carrier M, Vendittoli PA. Aspirin versus low-molecular-weight heparin for extended venous thromboembolism prophylaxis after total hip arthroplasty: a randomized trial. Ann Intern Med. 2013 Jun 4;158(11):800-6. [ | + | ## '''Subgroup analysis:''' Palumbo A, Cavo M, Bringhen S, Zamagni E, Romano A, Patriarca F, Rossi D, Gentilini F, Crippa C, Galli M, Nozzoli C, Ria R, Marasca R, Montefusco V, Baldini L, Elice F, Callea V, Pulini S, Carella AM, Zambello R, Benevolo G, Magarotto V, Tacchetti P, Pescosta N, Cellini C, Polloni C, Evangelista A, Caravita T, Morabito F, Offidani M, Tosi P, Boccadoro M. Aspirin, warfarin, or enoxaparin thromboprophylaxis in patients with multiple myeloma treated with thalidomide: a phase III, open-label, randomized trial. J Clin Oncol. 2011 Mar 10;29(8):986-93. Epub 2011 Jan 31. [https://doi.org/10.1200/JCO.2010.31.6844 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21282540/ PubMed] |
− | # '''EPCAT II:''' Anderson DR, Dunbar M, Murnaghan J, Kahn SR, Gross P, Forsythe M, Pelet S, Fisher W, Belzile E, Dolan S, Crowther M, Bohm E, MacDonald SJ, Gofton W, Kim P, Zukor D, Pleasance S, Andreou P, Doucette S, Theriault C, Abianui A, Carrier M, Kovacs MJ, Rodger MA, Coyle D, Wells PS, Vendittoli PA. Aspirin or rivaroxaban for VTE prophylaxis after hip or knee arthroplasty. N Engl J Med. 2018 Feb 22;378(8):699-707. [https:// | + | #'''MPRvsMEL200<sub>VTE</sub>:''' Larocca A, Cavallo F, Bringhen S, Di Raimondo F, Falanga A, Evangelista A, Cavalli M, Stanevsky A, Corradini P, Pezzatti S, Patriarca F, Cavo M, Peccatori J, Catalano L, Carella AM, Cafro AM, Siniscalchi A, Crippa C, Petrucci MT, Yehuda DB, Beggiato E, Di Toritto TC, Boccadoro M, Nagler A, Palumbo A. Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide. Blood. 2012 Jan 26;119(4):933-9. Epub 2011 Aug 11. [https://doi.org/10.1182/blood-2011-03-344333 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21835953/ PubMed] [https://clinicaltrials.gov/study/NCT00551928 NCT00551928] |
+ | #'''EPCAT:''' Anderson DR, Dunbar MJ, Bohm ER, Belzile E, Kahn SR, Zukor D, Fisher W, Gofton W, Gross P, Pelet S, Crowther M, MacDonald S, Kim P, Pleasance S, Davis N, Andreou P, Wells P, Kovacs M, Rodger MA, Ramsay T, Carrier M, Vendittoli PA. Aspirin versus low-molecular-weight heparin for extended venous thromboembolism prophylaxis after total hip arthroplasty: a randomized trial. Ann Intern Med. 2013 Jun 4;158(11):800-6. [https://doi.org/10.7326/0003-4819-158-11-201306040-00004 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23732713/ PubMed] ISRCTN11902170 | ||
+ | #'''EPCAT II:''' Anderson DR, Dunbar M, Murnaghan J, Kahn SR, Gross P, Forsythe M, Pelet S, Fisher W, Belzile E, Dolan S, Crowther M, Bohm E, MacDonald SJ, Gofton W, Kim P, Zukor D, Pleasance S, Andreou P, Doucette S, Theriault C, Abianui A, Carrier M, Kovacs MJ, Rodger MA, Coyle D, Wells PS, Vendittoli PA. Aspirin or rivaroxaban for VTE prophylaxis after hip or knee arthroplasty. N Engl J Med. 2018 Feb 22;378(8):699-707. [https://doi.org/10.1056/NEJMoa1712746 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29466159/ PubMed] [https://clinicaltrials.gov/study/NCT01720108 NCT01720108] | ||
+ | #'''PREVENT CLOT:''' O'Toole RV, Stein DM, O'Hara NN, Frey KP, Taylor TJ, Scharfstein DO, Carlini AR, Sudini K, Degani Y, Slobogean GP, Haut ER, Obremskey W, Firoozabadi R, Bosse MJ, Goldhaber SZ, Marvel D, Castillo RC. Aspirin or Low-Molecular-Weight Heparin for Thromboprophylaxis after a Fracture. N Engl J Med. 2023 Jan 19;388(3):203-213. [https://doi.org/10.1056/NEJMoa2205973 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36652352/ PubMed] [https://clinicaltrials.gov/study/NCT02984384 NCT02984384] | ||
==Betrixaban monotherapy {{#subobject:834d5c|Regimen=1}}== | ==Betrixaban monotherapy {{#subobject:834d5c|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:f70ffb|Variant=1}}=== | ===Regimen {{#subobject:f70ffb|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | ! style="width: | + | !style="width: 20%"|Study |
− | ! style="width: | + | !style="width: 20%"|Dates of enrollment |
− | ! style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ! style="width: | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1601747 Cohen et al. 2016 (APEX-VTE)] |
− | | style="background-color:#1a9851" |Phase | + | |2012-03 to 2015-11 |
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
|[[#Enoxaparin_monotherapy|Enoxaparin]] | |[[#Enoxaparin_monotherapy|Enoxaparin]] | ||
− | | style="background-color:#d9ef8b" |Might have lower rates of VTE | + | | style="background-color:#d9ef8b" |Might have lower rates of VTE (primary endpoint) |
|- | |- | ||
|} | |} | ||
''Note: this APEX trial should not be confused with the one in multiple myeloma.'' | ''Note: this APEX trial should not be confused with the one in multiple myeloma.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
− | *[[Betrixaban (Bevyxxa)]] 80 mg PO once per day | + | *[[Betrixaban (Bevyxxa)]] 160 mg PO once on day 1, then 80 mg PO once per day |
+ | '''35- to 42-day course''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''APEX:''' Cohen AT, Harrington RA, Goldhaber SZ, Hull RD, Wiens BL, Gold A, Hernandez AF, Gibson CM; APEX Investigators. Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med. 2016 Aug 11;375(6):534-44. Epub 2016 May 27. [https:// | + | #'''APEX-VTE:''' Cohen AT, Harrington RA, Goldhaber SZ, Hull RD, Wiens BL, Gold A, Hernandez AF, Gibson CM; APEX Investigators. Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med. 2016 Aug 11;375(6):534-44. Epub 2016 May 27. [https://doi.org/10.1056/NEJMoa1601747 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27232649/ PubMed] [https://clinicaltrials.gov/study/NCT01583218 NCT01583218] |
− | |||
==Enoxaparin monotherapy {{#subobject:f7bdac|Regimen=1}}== | ==Enoxaparin monotherapy {{#subobject:f7bdac|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #1, 30 mg every 12 hours {{#subobject:a4d4d8|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | !style="width: 17%"|Study | |
− | === | + | !style="width: 15%"|Dates of enrollment |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ! style="width: | + | !style="width: 17%"|Comparator |
− | ! style="width: | + | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | ! style="width: | + | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] |
− | ! style="width: | ||
− | ! style="width: | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM199609053351003 Geerts et al. 1996] |
− | | style="background-color:#1a9851" |Phase | + | |1992-11 to 1994-11 |
− | | | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
+ | |[[#Heparin_monotherapy|UFH]] | ||
| style="background-color:#1a9850" |Superior DVT rates | | style="background-color:#1a9850" |Superior DVT rates | ||
| style="background-color:#ffffbf" |No difference in major bleeding rate | | style="background-color:#ffffbf" |No difference in major bleeding rate | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa0810773 Lassen et al. 2009 (ADVANCE-1)]] |
− | | style="background-color:#1a9851" |Phase | + | |Not reported |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Apixaban_monotherapy|Apixaban]] | |[[#Apixaban_monotherapy|Apixaban]] | ||
− | | style="background-color:#ffffbf" | | + | | style="background-color:#ffffbf" |Inconclusive whether non-inferior asymptomatic and symptomatic DVT, nonfatal PE, and death from any cause during treatment |
| style="background-color:#fc8d59" |Seems to have higher bleeding rate | | style="background-color:#fc8d59" |Seems to have higher bleeding rate | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/NEJMoa2205973 O'Toole et al. 2023 (PREVENT CLOT)] | ||
+ | |2017-04 to 2021-08 | ||
+ | | style="background-color:#1a9851" |Randomized (E-esc) | ||
+ | |[[#Aspirin_monotherapy|Aspirin]] | ||
+ | | style="background-color:#eeee01" |Non-inferior death rate at 90 days (primary endpoint) | ||
+ | | | ||
+ | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *Total knee replacement | + | *ADVANCE-1: Total knee replacement |
*The study population in Geerts et. al. were trauma patients without intracranial hemorrhage. Prophylaxis was initiated within 36 hours of the injury. | *The study population in Geerts et. al. were trauma patients without intracranial hemorrhage. Prophylaxis was initiated within 36 hours of the injury. | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
− | *[[Enoxaparin (Lovenox)]] 30 mg SC every 12 hours, beginning 12 to 24 h after wound closure (ADVANCE-1), 10- to 14-day course | + | *[[Enoxaparin (Lovenox)]] 30 mg SC every 12 hours, beginning 12 to 24 h after wound closure (ADVANCE-1), 10- to 14-day course |
− | *The comparison arm in Geerts et al. used heparin 5000 units subcutaneous every 12 hours. | + | *The comparison arm in Geerts et al. used heparin 5000 units subcutaneous every 12 hours. |
− | + | </div></div><br> | |
− | === | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | ===Regimen variant #2, 40 mg daily {{#subobject:8e940e|Variant=1}}=== |
− | ! style="width: | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | ! style="width: | + | !style="width: 20%"|Study |
− | ! style="width: | + | !style="width: 20%"|Dates of enrollment |
− | ! style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/NEJM199909093411103 Samama et al. 1999 (MEDENOX)] | ||
+ | |1996-12 to 1998-07 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1. [[Venous_thromboembolism_-_null_regimens#Placebo|Placebo]]<br>2. [[#Enoxaparin_monotherapy|Enoxaparin]]; 20 mg daily | ||
+ | | style="background-color:#1a9850" |Superior VTE rates | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.7326/0003-4819-153-1-201007060-00004 Hull et al. 2010 (EXCLAIM)] |
− | |Phase | + | |2002-02 to 2006-03 |
− | |Placebo | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | |Superior VTE | + | |[[Venous_thromboembolism_-_null_regimens#Placebo|Placebo]] |
+ | | style="background-color:#1a9850" |Superior composite VTE rate (primary endpoint) | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa0800374 Erikkson et al. 2008 (RECORD1)] |
− | | style="background-color:#1a9851" |Phase | + | |2006-02 to 2007-03 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Rivaroxaban_monotherapy|Rivaroxaban]] | |[[#Rivaroxaban_monotherapy|Rivaroxaban]] | ||
| style="background-color:#d73027" |Inferior composite outcome | | style="background-color:#d73027" |Inferior composite outcome | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(08)60880-6 Kakkar et al. 2008 (RECORD2)] |
− | | style="background-color:#1a9851" |Phase | + | |2006-02 to 2007-04 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Rivaroxaban_monotherapy|Rivaroxaban]] | |[[#Rivaroxaban_monotherapy|Rivaroxaban]] | ||
| style="background-color:#d73027" |Inferior composite outcome | | style="background-color:#d73027" |Inferior composite outcome | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa076016 Lassen et al. 2008 (RECORD3)] |
− | | style="background-color:#1a9851" |Phase | + | |2006-02 to 2006-11 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Rivaroxaban_monotherapy|Rivaroxaban]] | |[[#Rivaroxaban_monotherapy|Rivaroxaban]] | ||
| style="background-color:#d73027" |Inferior composite outcome | | style="background-color:#d73027" |Inferior composite outcome | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1200/JCO.2010.31.6844 Palumbo et al. 2011 (GIMEMA MM-03-05)] |
− | | style="background-color:#1a9851" |Phase | + | |2006-05 to 2009-01 |
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
+ | |1. [[#Aspirin_monotherapy|Aspirin]]<br>2. [[#Warfarin_monotherapy_888|Warfarin]]; low-dose | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of serious thromboembolic events, acute cardiovascular events, or sudden deaths during the first 6 months of treatment | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S0140-6736(09)60734-0 Turpie et al. 2009 (RECORD4)] | ||
+ | |2006-06 to 2007-10 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Rivaroxaban_monotherapy|Rivaroxaban]] | |[[#Rivaroxaban_monotherapy|Rivaroxaban]] | ||
| style="background-color:#fc8d59" |Seems to have inferior composite outcome | | style="background-color:#fc8d59" |Seems to have inferior composite outcome | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1006885 Lassen et al. 2010 (ADVANCE-3)] |
− | | style="background-color:#1a9851" |Phase | + | |2007-03 to 2009-05 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Apixaban_monotherapy|Apixaban]] | |[[#Apixaban_monotherapy|Apixaban]] | ||
− | | style="background-color:#d73027" |Inferior composite | + | | style="background-color:#d73027" |Inferior composite primary endpoint |
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1056/NEJMoa1110899 Goldhaber et al. 2011 (ADOPT)] |
− | | style="background-color:#1a9851" |Phase | + | |2007-06 to 2011-02 |
− | |[[# | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | | style="background-color:# | + | |[[#Apixaban_monotherapy|Apixaban]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of 30-day composite of death related to venous thromboembolism, pulmonary embolism, symptomatic deep-vein thrombosis, or asymptomatic proximal-leg deep-vein thrombosis | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(09)62125-5 Lassen et al. 2010 (ADVANCE-2)] |
− | | style="background-color:#1a9851" |Phase | + | |2007-06-29 to 2008-11-12 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Apixaban_monotherapy|Apixaban]] | |[[#Apixaban_monotherapy|Apixaban]] | ||
− | | style="background-color:#d73027" |Inferior composite | + | | style="background-color:#d73027" |Inferior composite primary endpoint |
− | |||
− | |||
− | |||
− | |||
− | |||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2011-03-344333 Larocca et al. 2011 (MPRvsMEL200<sub>VTE</sub>)] |
− | | style="background-color:#1a9851" |Phase | + | |2007-11 to 2009-06 |
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
|[[#Aspirin_monotherapy|Aspirin]] | |[[#Aspirin_monotherapy|Aspirin]] | ||
− | | style="background-color:#ffffbf" | | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of VTE incidence |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1111096 Cohen et al. 2013 (MAGELLAN)] |
− | | style="background-color:#1a9851" |Phase | + | |2007-12 to 2010-07 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Rivaroxaban_monotherapy|Rivaroxaban]] | |[[#Rivaroxaban_monotherapy|Rivaroxaban]] | ||
| style="background-color:#eeee01" |Non-inferior VTE rate at 10 days | | style="background-color:#eeee01" |Non-inferior VTE rate at 10 days | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1111288 Kakkar et al. 2011 (LIFENOX)] |
− | | style="background-color:#1a9851" |Phase | + | |2008-01 to 2010-09 |
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |[[Venous_thromboembolism_-_null_regimens#Placebo|Placebo]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of death rate at 30 days | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/NEJMoa1601747 Cohen et al. 2016 (APEX-VTE)] | ||
+ | |2012-03 to 2015-11 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Betrixaban_monotherapy|Betrixaban]] | |[[#Betrixaban_monotherapy|Betrixaban]] | ||
| style="background-color:#fee08b" |Might have higher rates of VTE | | style="background-color:#fee08b" |Might have higher rates of VTE | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9399863/ Sidhu et al. 2022 (CRISTAL)] | ||
+ | |2019-04-20 to 2020-12-18 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Aspirin_monotherapy|Aspirin]] | ||
+ | | style="background-color:#1a9850" |Superior rate of symptomatic VTE within 90 days | ||
|- | |- | ||
|} | |} | ||
− | ''Note: the APEX trial here should not be confused with the one in multiple myeloma.'' | + | ''Note: the APEX trial here should not be confused with the one in multiple myeloma. Larocca et al. 2011 was a substudy looking at thromboprophylaxis in the lenalidomide arm.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *ADVANCE-2: Total knee replacement | + | *ADVANCE-2 & CRISTAL: Total knee replacement |
− | *ADVANCE-3: Total hip replacement | + | *ADVANCE-3 & CRISTAL: Total hip replacement |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
*[[Enoxaparin (Lovenox)]] 40 mg SC once per day | *[[Enoxaparin (Lovenox)]] 40 mg SC once per day | ||
− | + | '''Various durations: 6 to 14 days (APEX-VTE); other (see papers for details)''' | |
− | '''Various durations (see papers for details)''' | + | </div></div> |
===References=== | ===References=== | ||
− | # Geerts WH, Jay RM, Code KI, Chen E, Szalai JP, Saibil EA, Hamilton PA. A comparison of low-dose heparin with low-molecular-weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med. 1996 Sep 5;335(10):701-7. [https:// | + | #Geerts WH, Jay RM, Code KI, Chen E, Szalai JP, Saibil EA, Hamilton PA. A comparison of low-dose heparin with low-molecular-weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med. 1996 Sep 5;335(10):701-7. [https://doi.org/10.1056/NEJM199609053351003 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8703169/ PubMed] |
− | # '''MEDENOX:''' Samama MM, Cohen AT, Darmon JY, Desjardins L, Eldor A, Janbon C, Leizorovicz A, Nguyen H, Olsson CG, Turpie AG, Weisslinger N; MEDENOX Investigators. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. N Engl J Med. 1999; 341:793-800. [https:// | + | #'''MEDENOX:''' Samama MM, Cohen AT, Darmon JY, Desjardins L, Eldor A, Janbon C, Leizorovicz A, Nguyen H, Olsson CG, Turpie AG, Weisslinger N; MEDENOX Investigators. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. N Engl J Med. 1999; 341:793-800. [https://doi.org/10.1056/NEJM199909093411103 link to original article]. [https://pubmed.ncbi.nlm.nih.gov/10477777/ PubMed]. |
− | # '''RECORD2:''' Kakkar AK, Brenner B, Dahl OE, Eriksson BI, Mouret P, Muntz J, Soglian AG, Pap AF, Misselwitz F, Haas S; RECORD2 Investigators. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet. 2008 Jul 5;372(9632):31-9. Epub 2008 Jun 24. [https:// | + | #'''RECORD2:''' Kakkar AK, Brenner B, Dahl OE, Eriksson BI, Mouret P, Muntz J, Soglian AG, Pap AF, Misselwitz F, Haas S; RECORD2 Investigators. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet. 2008 Jul 5;372(9632):31-9. Epub 2008 Jun 24. [https://doi.org/10.1016/S0140-6736(08)60880-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18582928/ PubMed] [https://clinicaltrials.gov/study/NCT00332020 NCT00332020] |
− | # '''RECORD1:''' Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, Bandel TJ, Beckmann H, Muehlhofer E, Misselwitz F, Geerts W; RECORD1 Study Group. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008 Jun 26;358(26):2765-75. [https:// | + | #'''RECORD1:''' Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, Bandel TJ, Beckmann H, Muehlhofer E, Misselwitz F, Geerts W; RECORD1 Study Group. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008 Jun 26;358(26):2765-75. [https://doi.org/10.1056/NEJMoa0800374 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18579811/ PubMed] [https://clinicaltrials.gov/study/NCT00329628 NCT00329628] |
− | + | #'''RECORD3:''' Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, Misselwitz F, Turpie AG; RECORD3 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008 Jun 26;358(26):2776-86. [https://doi.org/10.1056/NEJMoa076016 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18579812/ PubMed] [https://clinicaltrials.gov/study/NCT00361894 NCT00361894] | |
− | + | #'''RECORD4:''' Turpie AG, Lassen MR, Davidson BL, Bauer KA, Gent M, Kwong LM, Cushner FD, Lotke PA, Berkowitz SD, Bandel TJ, Benson A, Misselwitz F, Fisher WD; RECORD4 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. 2009 May 16;373(9676):1673-80. Epub 2009 May 4. [https://doi.org/10.1016/S0140-6736(09)60734-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19411100/ PubMed] [https://clinicaltrials.gov/study/NCT00362232 NCT00362232] | |
− | + | #'''ADVANCE-1:''' Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Portman RJ. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med. 2009 Aug 6;361(6):594-604. Erratum in: N Engl J Med. 2009 Oct 29;361(18):1814. [https://doi.org/10.1056/NEJMoa0810773 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19657123/ PubMed] [https://clinicaltrials.gov/study/NCT00371683 NCT00371683] | |
− | # '''ADVANCE-2:''' Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P; ADVANCE-2 investigators. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet. 2010 Mar 6;375(9717):807-15. [https:// | + | #'''ADVANCE-2:''' Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P; ADVANCE-2 investigators. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet. 2010 Mar 6;375(9717):807-15. [https://doi.org/10.1016/S0140-6736(09)62125-5 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20206776/ PubMed] [https://clinicaltrials.gov/study/NCT00452530 NCT00452530] |
− | # '''EXCLAIM:''' Hull RD, Schellong SM, Tapson VF, Monreal M, Samama MM, Nicol P, Vicaut E, Turpie AG, Yusen RD; EXCLAIM (Extended Prophylaxis for Venous ThromboEmbolism in Acutely Ill Medical Patients With Prolonged Immobilization) study. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial. Ann Intern Med. 2010 Jul 6;153(1):8-18. [ | + | #'''EXCLAIM:''' Hull RD, Schellong SM, Tapson VF, Monreal M, Samama MM, Nicol P, Vicaut E, Turpie AG, Yusen RD; EXCLAIM (Extended Prophylaxis for Venous ThromboEmbolism in Acutely Ill Medical Patients With Prolonged Immobilization) study. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial. Ann Intern Med. 2010 Jul 6;153(1):8-18. [https://doi.org/10.7326/0003-4819-153-1-201007060-00004 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20621900/ PubMed] [https://clinicaltrials.gov/study/NCT00077753 NCT00077753] |
− | # '''ADVANCE-3:''' Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM; ADVANCE-3 Investigators. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med. 2010 Dec 23;363(26):2487-98. [https:// | + | #'''ADVANCE-3:''' Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM; ADVANCE-3 Investigators. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med. 2010 Dec 23;363(26):2487-98. [https://doi.org/10.1056/NEJMoa1006885 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21175312/ PubMed] [https://clinicaltrials.gov/study/NCT00423319 NCT00423319] |
− | # Palumbo A, Cavo M, Bringhen S, Zamagni E, Romano A, Patriarca F, Rossi D, Gentilini F, Crippa C, Galli M, Nozzoli C, Ria R, Marasca R, Montefusco V, Baldini L, Elice F, Callea V, Pulini S, Carella AM, Zambello R, Benevolo G, Magarotto V, Tacchetti P, Pescosta N, Cellini C, Polloni C, Evangelista A, Caravita T, Morabito F, Offidani M, Tosi P, Boccadoro M. Aspirin, warfarin, or enoxaparin thromboprophylaxis in patients with multiple myeloma treated with thalidomide: a phase III, open-label, randomized trial. J Clin Oncol. 2011 Mar 10;29(8):986-93. Epub 2011 Jan 31. [https:// | + | #'''GIMEMA MM-03-05:''' Palumbo A, Cavo M, Bringhen S, Zamagni E, Romano A, Patriarca F, Rossi D, Gentilini F, Crippa C, Galli M, Nozzoli C, Ria R, Marasca R, Montefusco V, Baldini L, Elice F, Callea V, Pulini S, Carella AM, Zambello R, Benevolo G, Magarotto V, Tacchetti P, Pescosta N, Cellini C, Polloni C, Evangelista A, Caravita T, Morabito F, Offidani M, Tosi P, Boccadoro M. Aspirin, warfarin, or enoxaparin thromboprophylaxis in patients with multiple myeloma treated with thalidomide: a phase III, open-label, randomized trial. J Clin Oncol. 2011 Mar 10;29(8):986-93. Epub 2011 Jan 31. [https://doi.org/10.1200/JCO.2010.31.6844 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21282540/ PubMed] [https://clinicaltrials.gov/study/NCT01063179 NCT01063179] |
− | # Larocca A, Cavallo F, Bringhen S, Di Raimondo F, Falanga A, Evangelista A, Cavalli M, Stanevsky A, Corradini P, Pezzatti S, Patriarca F, Cavo M, Peccatori J, Catalano L, Carella AM, Cafro AM, Siniscalchi A, Crippa C, Petrucci MT, Yehuda DB, Beggiato E, Di Toritto TC, Boccadoro M, Nagler A, Palumbo A. Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide. Blood. 2012 Jan 26;119(4):933-9. Epub 2011 Aug 11. [ | + | #'''MPRvsMEL200<sub>VTE</sub>:''' Larocca A, Cavallo F, Bringhen S, Di Raimondo F, Falanga A, Evangelista A, Cavalli M, Stanevsky A, Corradini P, Pezzatti S, Patriarca F, Cavo M, Peccatori J, Catalano L, Carella AM, Cafro AM, Siniscalchi A, Crippa C, Petrucci MT, Yehuda DB, Beggiato E, Di Toritto TC, Boccadoro M, Nagler A, Palumbo A. Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide. Blood. 2012 Jan 26;119(4):933-9. Epub 2011 Aug 11. [https://doi.org/10.1182/blood-2011-03-344333 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21835953/ PubMed] [https://clinicaltrials.gov/study/NCT00551928 NCT00551928] |
− | # '''ADOPT:''' Goldhaber SZ, Leizorovicz A, Kakkar AK, Haas SK, Merli G, Knabb RM, Weitz JI; ADOPT Trial Investigators. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med. 2011 Dec 8;365(23):2167-77. Epub 2011 Nov 13. [https:// | + | #'''ADOPT:''' Goldhaber SZ, Leizorovicz A, Kakkar AK, Haas SK, Merli G, Knabb RM, Weitz JI; ADOPT Trial Investigators. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med. 2011 Dec 8;365(23):2167-77. Epub 2011 Nov 13. [https://doi.org/10.1056/NEJMoa1110899 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22077144/ PubMed] [https://clinicaltrials.gov/study/NCT00457002 NCT00457002] |
− | + | #'''LIFENOX:''' Kakkar AK, Cimminiello C, Goldhaber SZ, Parakh R, Wang C, Bergmann JF; LIFENOX Investigators. Low-molecular-weight heparin and mortality in acutely ill medical patients. N Engl J Med. 2011 Dec 29;365(26):2463-72. [https://doi.org/10.1056/NEJMoa1111288 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22204723/ PubMed] [https://clinicaltrials.gov/study/NCT00622648 NCT00622648] | |
− | # '''MAGELLAN:''' Cohen AT, Spiro TE, Büller HR, Haskell L, Hu D, Hull R, Mebazaa A, Merli G, Schellong S, Spyropoulos AC, Tapson V; MAGELLAN Investigators. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med. 2013 Feb 7;368(6):513-23. [https:// | + | #'''MAGELLAN:''' Cohen AT, Spiro TE, Büller HR, Haskell L, Hu D, Hull R, Mebazaa A, Merli G, Schellong S, Spyropoulos AC, Tapson V; MAGELLAN Investigators. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med. 2013 Feb 7;368(6):513-23. [https://doi.org/10.1056/NEJMoa1111096 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23388003/ PubMed] [https://clinicaltrials.gov/study/NCT00571649 NCT00571649] |
− | # '''APEX:''' Cohen AT, Harrington RA, Goldhaber SZ, Hull RD, Wiens BL, Gold A, Hernandez AF, Gibson CM; APEX Investigators. Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med. 2016 Aug 11;375(6):534-44. Epub 2016 May 27. [https:// | + | #'''APEX-VTE:''' Cohen AT, Harrington RA, Goldhaber SZ, Hull RD, Wiens BL, Gold A, Hernandez AF, Gibson CM; APEX Investigators. Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med. 2016 Aug 11;375(6):534-44. Epub 2016 May 27. [https://doi.org/10.1056/NEJMoa1601747 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27232649/ PubMed] [https://clinicaltrials.gov/study/NCT01583218 NCT01583218] |
− | + | #'''CRISTAL:''' Sidhu VS, Kelly TL, Pratt N, Graves SE, Buchbinder R, Adie S, Cashman K, Ackerman I, Bastiras D, Brighton R, Burns AWR, Chong BH, Clavisi O, Cripps M, Dekkers M, de Steiger R, Dixon M, Ellis A, Griffith EC, Hale D, Hansen A, Harris A, Hau R, Horsley M, James D, Khorshid O, Kuo L, Lewis P, Lieu D, Lorimer M, MacDessi S, McCombe P, McDougall C, Mulford J, Naylor JM, Page RS, Radovanovic J, Solomon M, Sorial R, Summersell P, Tran P, Walter WL, Webb S, Wilson C, Wysocki D, Harris IA; CRISTAL Study Group. Effect of Aspirin vs Enoxaparin on Symptomatic Venous Thromboembolism in Patients Undergoing Hip or Knee Arthroplasty: The CRISTAL Randomized Trial. JAMA. 2022 Aug 23;328(8):719-727. [https://doi.org/10.1001/jama.2022.13416 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9399863/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35997730/ PubMed] ACTRN12618001879257 | |
− | + | #'''PREVENT CLOT:''' O'Toole RV, Stein DM, O'Hara NN, Frey KP, Taylor TJ, Scharfstein DO, Carlini AR, Sudini K, Degani Y, Slobogean GP, Haut ER, Obremskey W, Firoozabadi R, Bosse MJ, Goldhaber SZ, Marvel D, Castillo RC. Aspirin or Low-Molecular-Weight Heparin for Thromboprophylaxis after a Fracture. N Engl J Med. 2023 Jan 19;388(3):203-213. [https://doi.org/10.1056/NEJMoa2205973 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36652352/ PubMed] [https://clinicaltrials.gov/study/NCT02984384 NCT02984384] | |
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− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
==Rivaroxaban monotherapy {{#subobject:6a7fba|Regimen=1}}== | ==Rivaroxaban monotherapy {{#subobject:6a7fba|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:828315|Variant=1}}=== | ===Regimen {{#subobject:828315|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | ! style="width: | + | !style="width: 20%"|Study |
− | ! style="width: | + | !style="width: 20%"|Dates of enrollment |
− | ! style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ! style="width: | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa0800374 Erikkson et al. 2008 (RECORD1)] |
− | | style="background-color:#1a9851" |Phase | + | |2006-02 to 2007-03 |
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
|[[#Enoxaparin_monotherapy|Enoxaparin]] | |[[#Enoxaparin_monotherapy|Enoxaparin]] | ||
− | | style="background-color:#1a9850" |Superior composite outcome | + | | style="background-color:#1a9850" |Superior composite outcome (primary endpoint) |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(08)60880-6 Kakkar et al. 2008 (RECORD2)] |
− | | style="background-color:#1a9851" |Phase | + | |2006-02 to 2007-04 |
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
|[[#Enoxaparin_monotherapy|Enoxaparin]] | |[[#Enoxaparin_monotherapy|Enoxaparin]] | ||
− | | style="background-color:#1a9850" |Superior composite outcome | + | | style="background-color:#1a9850" |Superior composite outcome (primary endpoint) |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa076016 Lassen et al. 2008 (RECORD3)] |
− | | style="background-color:#1a9851" |Phase | + | |2006-02 to 2006-11 |
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
|[[#Enoxaparin_monotherapy|Enoxaparin]] | |[[#Enoxaparin_monotherapy|Enoxaparin]] | ||
− | | style="background-color:#1a9850" |Superior composite outcome | + | | style="background-color:#1a9850" |Superior composite outcome (primary endpoint) |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(09)60734-0 Turpie et al. 2009 (RECORD4)] |
− | | style="background-color:#1a9851" |Phase | + | |2006-06 to 2007-10 |
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
|[[#Enoxaparin_monotherapy|Enoxaparin]] | |[[#Enoxaparin_monotherapy|Enoxaparin]] | ||
− | | style="background-color:#91cf60" |Seems to have superior composite outcome | + | | style="background-color:#91cf60" |Seems to have superior composite outcome (primary endpoint) |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1111096 Cohen et al. 2013 (MAGELLAN)] |
− | | style="background-color:#1a9851" |Phase | + | |2007-12 to 2010-07 |
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
|[[#Enoxaparin_monotherapy|Enoxaparin]] | |[[#Enoxaparin_monotherapy|Enoxaparin]] | ||
− | | style="background-color:#eeee01" |Non-inferior VTE rate at 10 days | + | | style="background-color:#eeee01" |Non-inferior VTE rate at 10 days (co-primary endpoint) |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1712746 Anderson et al. 2018 (EPCAT II)] |
− | | style="background-color:#1a9851" |Phase | + | |2013-01 to 2016-04 |
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
|[[#Aspirin_monotherapy|Aspirin]] | |[[#Aspirin_monotherapy|Aspirin]] | ||
− | | style="background-color:#eeee01" |Non-inferior VTE rate at 90 days | + | | style="background-color:#eeee01" |Non-inferior VTE rate at 90 days (primary endpoint) |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1805090 Spyropoulos et al. 2018 (MARINER)] |
− | | style="background-color:#1a9851" |Phase | + | |2014-06 to 2018-01 |
− | |[[#Placebo|Placebo]] | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | | style="background-color:#ffffbf" | | + | |[[Venous_thromboembolism_-_null_regimens#Placebo|Placebo]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of symptomatic VTE or death due to VTE | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
*[[Rivaroxaban (Xarelto)]] 10 mg PO once per day for varying durations (see individual studies) | *[[Rivaroxaban (Xarelto)]] 10 mg PO once per day for varying durations (see individual studies) | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''RECORD2:''' Kakkar AK, Brenner B, Dahl OE, Eriksson BI, Mouret P, Muntz J, Soglian AG, Pap AF, Misselwitz F, Haas S; RECORD2 Investigators. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet. 2008 Jul 5;372(9632):31-9. Epub 2008 Jun 24. [https:// | + | #'''RECORD2:''' Kakkar AK, Brenner B, Dahl OE, Eriksson BI, Mouret P, Muntz J, Soglian AG, Pap AF, Misselwitz F, Haas S; RECORD2 Investigators. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet. 2008 Jul 5;372(9632):31-9. Epub 2008 Jun 24. [https://doi.org/10.1016/S0140-6736(08)60880-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18582928/ PubMed] [https://clinicaltrials.gov/study/NCT00332020 NCT00332020] |
− | # '''RECORD1:''' Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, Bandel TJ, Beckmann H, Muehlhofer E, Misselwitz F, Geerts W; RECORD1 Study Group. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008 Jun 26;358(26):2765-75. [https:// | + | #'''RECORD1:''' Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, Bandel TJ, Beckmann H, Muehlhofer E, Misselwitz F, Geerts W; RECORD1 Study Group. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008 Jun 26;358(26):2765-75. [https://doi.org/10.1056/NEJMoa0800374 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18579811/ PubMed] [https://clinicaltrials.gov/study/NCT00329628 NCT00329628] |
− | # '''RECORD3:''' Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, Misselwitz F, Turpie AG; RECORD3 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008 Jun 26;358(26):2776-86. [https:// | + | #'''RECORD3:''' Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, Misselwitz F, Turpie AG; RECORD3 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008 Jun 26;358(26):2776-86. [https://doi.org/10.1056/NEJMoa076016 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18579812/ PubMed] [https://clinicaltrials.gov/study/NCT00361894 NCT00361894] |
− | # '''RECORD4:''' Turpie AG, Lassen MR, Davidson BL, Bauer KA, Gent M, Kwong LM, Cushner FD, Lotke PA, Berkowitz SD, Bandel TJ, Benson A, Misselwitz F, Fisher WD; RECORD4 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. 2009 May 16;373(9676):1673-80. Epub 2009 May 4. [https:// | + | #'''RECORD4:''' Turpie AG, Lassen MR, Davidson BL, Bauer KA, Gent M, Kwong LM, Cushner FD, Lotke PA, Berkowitz SD, Bandel TJ, Benson A, Misselwitz F, Fisher WD; RECORD4 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. 2009 May 16;373(9676):1673-80. Epub 2009 May 4. [https://doi.org/10.1016/S0140-6736(09)60734-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19411100/ PubMed] [https://clinicaltrials.gov/study/NCT00362232 NCT00362232] |
− | # '''MAGELLAN:''' Cohen AT, Spiro TE, Büller HR, Haskell L, Hu D, Hull R, Mebazaa A, Merli G, Schellong S, Spyropoulos AC, Tapson V; MAGELLAN Investigators. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med. 2013 Feb 7;368(6):513-23. [https:// | + | #'''MAGELLAN:''' Cohen AT, Spiro TE, Büller HR, Haskell L, Hu D, Hull R, Mebazaa A, Merli G, Schellong S, Spyropoulos AC, Tapson V; MAGELLAN Investigators. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med. 2013 Feb 7;368(6):513-23. [https://doi.org/10.1056/NEJMoa1111096 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23388003/ PubMed] [https://clinicaltrials.gov/study/NCT00571649 NCT00571649] |
− | # '''EPCAT II:''' Anderson DR, Dunbar M, Murnaghan J, Kahn SR, Gross P, Forsythe M, Pelet S, Fisher W, Belzile E, Dolan S, Crowther M, Bohm E, MacDonald SJ, Gofton W, Kim P, Zukor D, Pleasance S, Andreou P, Doucette S, Theriault C, Abianui A, Carrier M, Kovacs MJ, Rodger MA, Coyle D, Wells PS, Vendittoli PA. Aspirin or rivaroxaban for VTE prophylaxis after hip or knee arthroplasty. N Engl J Med. 2018 Feb 22;378(8):699-707. [https:// | + | #'''EPCAT II:''' Anderson DR, Dunbar M, Murnaghan J, Kahn SR, Gross P, Forsythe M, Pelet S, Fisher W, Belzile E, Dolan S, Crowther M, Bohm E, MacDonald SJ, Gofton W, Kim P, Zukor D, Pleasance S, Andreou P, Doucette S, Theriault C, Abianui A, Carrier M, Kovacs MJ, Rodger MA, Coyle D, Wells PS, Vendittoli PA. Aspirin or rivaroxaban for VTE prophylaxis after hip or knee arthroplasty. N Engl J Med. 2018 Feb 22;378(8):699-707. [https://doi.org/10.1056/NEJMoa1712746 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29466159/ PubMed] [https://clinicaltrials.gov/study/NCT01720108 NCT01720108] |
− | # '''MARINER:''' Spyropoulos AC, Ageno W, Albers GW, Elliott CG, Halperin JL, Hiatt WR, Maynard GA, Steg PG, Weitz JI, Suh E, Spiro TE, Barnathan ES, Raskob GE; MARINER Investigators. Rivaroxaban for thromboprophylaxis after hospitalization for medical illness. N Engl J Med. 2018 Sep 20;379(12):1118-1127. Epub 2018 Aug 26. [https:// | + | #'''MARINER:''' Spyropoulos AC, Ageno W, Albers GW, Elliott CG, Halperin JL, Hiatt WR, Maynard GA, Steg PG, Weitz JI, Suh E, Spiro TE, Barnathan ES, Raskob GE; MARINER Investigators. Rivaroxaban for thromboprophylaxis after hospitalization for medical illness. N Engl J Med. 2018 Sep 20;379(12):1118-1127. Epub 2018 Aug 26. [https://doi.org/10.1056/NEJMoa1805090 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30145946/ PubMed] [https://clinicaltrials.gov/study/NCT02111564 NCT02111564] |
=VTE secondary prevention= | =VTE secondary prevention= | ||
==Apixaban monotherapy {{#subobject:94eb02|Regimen=1}}== | ==Apixaban monotherapy {{#subobject:94eb02|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #1, 2.5 mg twice per day {{#subobject:969d50|Variant=1}}=== | |
− | |||
− | |||
− | === | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
|<small>'''FDA-recommended dose'''</small> | |<small>'''FDA-recommended dose'''</small> | ||
|- | |- | ||
|} | |} | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | | rowspan="2" |[https:// | + | | rowspan="2" |[https://doi.org/10.1056/NEJMoa1207541 Agnelli et al. 2012 (AMPLIFY-EXT)] |
− | | rowspan="2" style="background-color:#1a9851" |Phase | + | |rowspan=2|2008-05 to 2011-07 |
− | |1. Apixaban 5 mg twice per day | + | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc) |
− | | style="background-color:#ffffbf" | | + | |1. [[#Apixaban_monotherapy_2|Apixaban]]; 5 mg twice per day |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of symptomatic recurrent VTE or death from any cause | ||
|- | |- | ||
− | |2. Placebo | + | |2. [[#Placebo_888|Placebo]] |
− | | style="background-color:#1a9850" |Superior | + | | style="background-color:#1a9850" |Superior symptomatic recurrent VTE or death from any cause |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
*Therapeutic anticoagulation x 6-12 mo | *Therapeutic anticoagulation x 6-12 mo | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
*[[Apixaban (Eliquis)]] 2.5 mg PO twice per day | *[[Apixaban (Eliquis)]] 2.5 mg PO twice per day | ||
− | |||
'''12-month course''' | '''12-month course''' | ||
− | + | </div></div><br> | |
− | === | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | ===Regimen variant #2, 5 mg twice per day {{#subobject:c7bfff0|Variant=1}}=== |
− | !style="width: | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | | rowspan="2" |[https:// | + | | rowspan="2" |[https://doi.org/10.1056/NEJMoa1207541 Agnelli et al. 2012 (AMPLIFY-EXT)] |
− | | rowspan="2" style="background-color:#1a9851" |Phase | + | |rowspan=2|2008-05 to 2011-07 |
− | |1. Apixaban 2.5 mg twice per day | + | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc) |
− | | style="background-color:#ffffbf" | | + | |1. [[#Apixaban_monotherapy_2|Apixaban]]; 2.5 mg twice per day |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of symptomatic recurrent VTE or death from any cause | ||
|- | |- | ||
− | |2. Placebo | + | |2. [[#Placebo_888|Placebo]] |
− | | style="background-color:#1a9850" |Superior | + | | style="background-color:#1a9850" |Superior symptomatic recurrent VTE or death from any cause |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
*Therapeutic anticoagulation x 6-12 mo | *Therapeutic anticoagulation x 6-12 mo | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
*[[Apixaban (Eliquis)]] 5 mg PO twice per day | *[[Apixaban (Eliquis)]] 5 mg PO twice per day | ||
− | |||
'''12-month course''' | '''12-month course''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''AMPLIFY-EXT:''' Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Porcari A, Raskob GE, Weitz JI; AMPLIFY-EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):699-708. Epub 2012 Dec 8. [https:// | + | #'''AMPLIFY-EXT:''' Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Porcari A, Raskob GE, Weitz JI; AMPLIFY-EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):699-708. Epub 2012 Dec 8. [https://doi.org/10.1056/NEJMoa1207541 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23216615/ PubMed] |
==Aspirin monotherapy {{#subobject:eb5633|Regimen=1}}== | ==Aspirin monotherapy {{#subobject:eb5633|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:e3079b|Variant=1}}=== | ===Regimen {{#subobject:e3079b|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | ! style="width: | + | !style="width: 17%"|Study |
− | ! style="width: | + | !style="width: 15%"|Dates of enrollment |
− | ! style="width: | + | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ! style="width: | + | !style="width: 17%"|Comparator |
− | ! style="width: | + | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1210384 Brighton et al. 2012 (ASPIRE-VTE)] |
− | | style="background-color:#1a9851" |Phase | + | |2003-05 to 2011-08 |
− | |Placebo | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | | style="background-color:# | + | |[[#Placebo_888|Placebo]] |
+ | | style="background-color:#d9ef8b" |Might have superior rate of VTE recurrence (primary endpoint) | ||
| style="background-color:#ffffbf" |No difference in bleeding rate | | style="background-color:#ffffbf" |No difference in bleeding rate | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1114238 Becattini et al. 2012 (WARFASA)] |
− | | style="background-color:#1a9851" |Phase | + | |2004-05 to 2010-08 |
− | |Placebo | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | | style="background-color:# | + | |[[#Placebo_888|Placebo]] |
+ | | style="background-color:#1a9850" |Superior rate of VTE recurrence (primary endpoint) | ||
| style="background-color:#ffffbf" |No difference in bleeding rate | | style="background-color:#ffffbf" |No difference in bleeding rate | ||
|- | |- | ||
|} | |} | ||
''Note: ASPIRE should not be confused with the multiple myeloma trial of the same name.'' | ''Note: ASPIRE should not be confused with the multiple myeloma trial of the same name.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
*WARFASA: [[#Warfarin_monotherapy|Warfarin]] x 6 to 18 months | *WARFASA: [[#Warfarin_monotherapy|Warfarin]] x 6 to 18 months | ||
*ASPIRE: [[#Warfarin_monotherapy|Warfarin]] x 6 weeks to 24 months | *ASPIRE: [[#Warfarin_monotherapy|Warfarin]] x 6 weeks to 24 months | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
*[[Aspirin]] 100 mg PO once per day | *[[Aspirin]] 100 mg PO once per day | ||
− | |||
'''Two or more years''' | '''Two or more years''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''WARFASA:''' Becattini C, Agnelli G, Schenone A, Eichinger S, Bucherini E, Silingardi M, Bianchi M, Moia M, Ageno W, Vandelli MR, Grandone E, Prandoni P; WARFASA Investigators. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med. 2012 May 24;366(21):1959-67. Erratum in: N Engl J Med. 2012 Oct 18;367(16):1573. [https:// | + | #'''WARFASA:''' Becattini C, Agnelli G, Schenone A, Eichinger S, Bucherini E, Silingardi M, Bianchi M, Moia M, Ageno W, Vandelli MR, Grandone E, Prandoni P; WARFASA Investigators. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med. 2012 May 24;366(21):1959-67. Erratum in: N Engl J Med. 2012 Oct 18;367(16):1573. [https://doi.org/10.1056/NEJMoa1114238 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22621626/ PubMed] [https://clinicaltrials.gov/study/NCT00222677 NCT00222677] |
− | # '''ASPIRE:''' Brighton TA, Eikelboom JW, Mann K, Mister R, Gallus A, Ockelford P, Gibbs H, Hague W, Xavier D, Diaz R, Kirby A, Simes J; ASPIRE Investigators. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med. 2012 Nov 22;367(21):1979-87. Epub 2012 Nov 4. [https:// | + | #'''ASPIRE-VTE:''' Brighton TA, Eikelboom JW, Mann K, Mister R, Gallus A, Ockelford P, Gibbs H, Hague W, Xavier D, Diaz R, Kirby A, Simes J; ASPIRE Investigators. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med. 2012 Nov 22;367(21):1979-87. Epub 2012 Nov 4. [https://doi.org/10.1056/NEJMoa1210384 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23121403/ PubMed] ACTRN12605000004662 |
− | |||
==Dalteparin monotherapy {{#subobject:57c5b7|Regimen=1}}== | ==Dalteparin monotherapy {{#subobject:57c5b7|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:cbc29a|Variant=1}}=== | ===Regimen {{#subobject:cbc29a|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | ! style="width: | + | !style="width: 17%"|Study |
− | ! style="width: | + | !style="width: 15%"|Dates of enrollment |
− | ! style="width: | + | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ! style="width: | + | !style="width: 17%"|Comparator |
− | ! style="width: | + | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa025313 Lee et al. 2003 (CLOT)] |
− | | style="background-color:#1a9851" |Phase | + | |1999-05 to 2001-10 |
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
|[[#Warfarin_monotherapy|Warfarin]] | |[[#Warfarin_monotherapy|Warfarin]] | ||
− | | style="background-color:#1a9850" |Superior rate of VTE at 6 months | + | | style="background-color:#1a9850" |Superior rate of VTE at 6 months (primary endpoint) |
| style="background-color:#ffffbf" |No difference in bleeding rate | | style="background-color:#ffffbf" |No difference in bleeding rate | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
*[[Dalteparin (Fragmin)]] as follows: | *[[Dalteparin (Fragmin)]] as follows: | ||
− | ** | + | **Month 1: 200 IU/kg SC once per day |
− | ** | + | **Months 2 to 6: 150 IU/kg SC once per day |
− | |||
'''6-month course''' | '''6-month course''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''CLOT:''' Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M; Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003 Jul 10;349(2):146-53. [https:// | + | #'''CLOT:''' Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M; Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003 Jul 10;349(2):146-53. [https://doi.org/10.1056/NEJMoa025313 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12853587/ PubMed] |
− | ## ''' | + | ##'''Post-hoc analysis:''' Lee AY, Rickles FR, Julian JA, Gent M, Baker RI, Bowden C, Kakkar AK, Prins M, Levine MN. Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism. J Clin Oncol. 2005 Apr 1;23(10):2123-9. Epub 2005 Feb 7. [https://doi.org/10.1200/jco.2005.03.133 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15699480/ PubMed] |
− | |||
==Enoxaparin monotherapy {{#subobject:30d50d|Regimen=1}}== | ==Enoxaparin monotherapy {{#subobject:30d50d|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:a64a42|Variant=1}}=== | ===Regimen {{#subobject:a64a42|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | ! style="width: | + | !style="width: 20%"|Study |
− | ! style="width: | + | !style="width: 20%"|Dates of enrollment |
− | ! style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ! style="width: | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[http://archinte. | + | |[http://doi.org/10.1001/archinte.162.15.1729 Meyer et al. 2002] |
− | | style="background-color:#1a9851" |Phase | + | |1995-04 to 1999-03 |
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
|[[#Warfarin_monotherapy|Warfarin]] | |[[#Warfarin_monotherapy|Warfarin]] | ||
− | | style="background-color:#d9ef8b" |Might have superior | + | | style="background-color:#d9ef8b" |Might have superior composite VTE/bleeding outcome (primary endpoint) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
*[[Enoxaparin (Lovenox)]] 1.5 mg/kg SC once per day | *[[Enoxaparin (Lovenox)]] 1.5 mg/kg SC once per day | ||
− | |||
'''3-month course''' | '''3-month course''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Meyer G, Marjanovic Z, Valcke J, Lorcerie B, Gruel Y, Solal-Celigny P, Le Maignan C, Extra JM, Cottu P, Farge D. Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. Arch Intern Med. 2002 Aug 12-26;162(15):1729-35. [http://archinte. | + | #Decousus H, Leizorovicz A, Parent F, Page Y, Tardy B, Girard P, Laporte S, Faivre R, Charbonnier B, Barral FG, Huet Y, Simonneau G; Prévention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group. A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. N Engl J Med. 1998 Feb 12;338(7):409-15. [https://doi.org/10.1056/nejm199802123380701 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9459643/ PubMed] |
+ | #Meyer G, Marjanovic Z, Valcke J, Lorcerie B, Gruel Y, Solal-Celigny P, Le Maignan C, Extra JM, Cottu P, Farge D. Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. Arch Intern Med. 2002 Aug 12-26;162(15):1729-35. [http://doi.org/10.1001/archinte.162.15.1729 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12153376/ PubMed] | ||
+ | #'''Highlow:''' Bistervels IM, Buchmüller A, Wiegers HMG, Ní Áinle F, Tardy B, Donnelly J, Verhamme P, Jacobsen AF, Hansen AT, Rodger MA, DeSancho MT, Shmakov RG, van Es N, Prins MH, Chauleur C, Middeldorp S; Highlow Block writing committee; Highlow Investigators. Intermediate-dose versus low-dose low-molecular-weight heparin in pregnant and post-partum women with a history of venous thromboembolism (Highlow study): an open-label, multicentre, randomised, controlled trial. Lancet. 2022 Oct 28:S0140-6736(22)02128-6. [https://doi.org/10.1016/s0140-6736(22)02128-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36354038/ PubMed] [https://clinicaltrials.gov/study/NCT01828697 NCT01828697] | ||
==Warfarin monotherapy {{#subobject:acc688|Regimen=1}}== | ==Warfarin monotherapy {{#subobject:acc688|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #1, standard intensity {{#subobject:3eda79|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | !style="width: 17%"|Study | |
− | === | + | !style="width: 15%"|Dates of enrollment |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ! style="width: | + | !style="width: 17%"|Comparator |
− | ! style="width: | + | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | ! style="width: | + | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] |
− | ! style="width: | ||
− | ! style="width: | ||
|- | |- | ||
− | |[http://archinte. | + | |[http://doi.org/10.1001/archinte.162.15.1729 Meyer et al. 2002] |
− | | style="background-color:#1a9851" |Phase | + | |1995-04-02 to 1999-03-31 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Enoxaparin_monotherapy_2|Enoxaparin]] | |[[#Enoxaparin_monotherapy_2|Enoxaparin]] | ||
− | | style="background-color:#fee08b" |Might have inferior | + | | style="background-color:#fee08b" |Might have inferior composite VTE/bleeding outcome |
| | | | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa025313 Lee et al. 2003 (CLOT)] |
− | | style="background-color:#1a9851" |Phase | + | |1999-05 to 2001-10 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Dalteparin_monotherapy|Dalteparin]] | |[[#Dalteparin_monotherapy|Dalteparin]] | ||
| style="background-color:#d73027" |Inferior rate of VTE at 6 months | | style="background-color:#d73027" |Inferior rate of VTE at 6 months | ||
Line 642: | Line 697: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
− | *[[Warfarin (Coumadin)]] PO titrated to goal INR 2 | + | *[[Warfarin (Coumadin)]] PO titrated to goal INR 2 to 3.0 |
− | + | </div></div><br> | |
− | === | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | ===Regimen variant #2, low intensity {{#subobject:7c40af|Variant=1}}=== |
− | ! style="width: | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | ! style="width: | + | !style="width: 17%"|Study |
− | ! style="width: | + | !style="width: 15%"|Dates of enrollment |
− | ! style="width: | + | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ! style="width: | + | !style="width: 17%"|Comparator |
+ | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa035029 Ridker et al. 2003 (PREVENT)] |
− | | style="background-color:#1a9851" |Phase | + | |1998-07-06 to 2002-12-04 |
− | |Placebo | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | | style="background-color:#1a9850" |Superior recurrent VTE rate | + | |[[#Placebo_888|Placebo]] |
+ | | style="background-color:#1a9850" |Superior recurrent VTE rate (primary endpoint) | ||
| style="background-color:#ffffbf" |No difference in major bleeding | | style="background-color:#ffffbf" |No difference in major bleeding | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *Warfarin with goal INR of 2 | + | *Warfarin with goal INR of 2 to 3 for median of 6.5 mo |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
*[[Warfarin (Coumadin)]] PO titrated to goal INR 1.5 to 2.0 | *[[Warfarin (Coumadin)]] PO titrated to goal INR 1.5 to 2.0 | ||
− | |||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Meyer G, Marjanovic Z, Valcke J, Lorcerie B, Gruel Y, Solal-Celigny P, Le Maignan C, Extra JM, Cottu P, Farge D. Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. Arch Intern Med. 2002 Aug 12-26;162(15):1729-35. [http://archinte. | + | #Meyer G, Marjanovic Z, Valcke J, Lorcerie B, Gruel Y, Solal-Celigny P, Le Maignan C, Extra JM, Cottu P, Farge D. Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. Arch Intern Med. 2002 Aug 12-26;162(15):1729-35. [http://doi.org/10.1001/archinte.162.15.1729 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12153376/ PubMed] |
− | # '''PREVENT:''' Ridker PM, Goldhaber SZ, Danielson E, Rosenberg Y, Eby CS, Deitcher SR, Cushman M, Moll S, Kessler CM, Elliott CG, Paulson R, Wong T, Bauer KA, Schwartz BA, Miletich JP, Bounameaux H, Glynn RJ; PREVENT Investigators. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med. 2003 Apr 10;348(15):1425-34. Epub 2003 Feb 24. [https:// | + | #Kearon C, Ginsberg JS, Kovacs MJ, Anderson DR, Wells P, Julian JA, MacKinnon B, Weitz JI, Crowther MA, Dolan S, Turpie AG, Geerts W, Solymoss S, van Nguyen P, Demers C, Kahn SR, Kassis J, Rodger M, Hambleton J, Gent M; Extended Low-Intensity Anticoagulation for Thrombo-Embolism Investigators. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med. 2003 Aug 14;349(7):631-9. [https://doi.org/10.1056/nejmoa035422 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12917299/ PubMed] |
− | # '''CLOT:''' Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M; Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003 Jul 10;349(2):146-53. [https:// | + | #'''PREVENT:''' Ridker PM, Goldhaber SZ, Danielson E, Rosenberg Y, Eby CS, Deitcher SR, Cushman M, Moll S, Kessler CM, Elliott CG, Paulson R, Wong T, Bauer KA, Schwartz BA, Miletich JP, Bounameaux H, Glynn RJ; PREVENT Investigators. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med. 2003 Apr 10;348(15):1425-34. Epub 2003 Feb 24. [https://doi.org/10.1056/NEJMoa035029 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12601075/ PubMed] |
− | ## ''' | + | #'''CLOT:''' Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M; Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003 Jul 10;349(2):146-53. [https://doi.org/10.1056/NEJMoa025313 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12853587/ PubMed] |
− | + | ##'''Post-hoc analysis:''' Lee AY, Rickles FR, Julian JA, Gent M, Baker RI, Bowden C, Kakkar AK, Prins M, Levine MN. Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism. J Clin Oncol. 2005 Apr 1;23(10):2123-9. Epub 2005 Feb 7. [https://doi.org/10.1200/jco.2005.03.133 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15699480/ PubMed] | |
=VTE treatment, all lines of therapy= | =VTE treatment, all lines of therapy= | ||
==Apixaban monotherapy {{#subobject:f80057|Regimen=1}}== | ==Apixaban monotherapy {{#subobject:f80057|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:856942|Variant=1}}=== | ===Regimen {{#subobject:856942|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
Line 684: | Line 742: | ||
|- | |- | ||
|} | |} | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !Study | + | !style="width: 17%"|Study |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | !style="width: 15%"|Dates of enrollment |
− | !Comparator | + | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ![[Levels_of_Evidence# | + | !style="width: 17%"|Comparator |
− | ![[Levels_of_Evidence#Toxicity|Toxicity]] | + | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1302507 Agnelli et al. 2013 (AMPLIFY)] |
− | | style="background-color:#1a9851" |Phase | + | |2008-08 to 2012-08 |
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | ||
|[[#Warfarin_monotherapy_2|Warfarin]] | |[[#Warfarin_monotherapy_2|Warfarin]] | ||
− | | style="background-color:#eeee01" |Non-inferior composite endpoint | + | | style="background-color:#eeee01" |Non-inferior composite primary endpoint |
| style="background-color:#1a9850" |Lower rates of bleeding | | style="background-color:#1a9850" |Lower rates of bleeding | ||
+ | |- | ||
+ | |[https://doi.org/10.1111/jth.14662 McBane et al. 2019 (ADAM VTE)] | ||
+ | |2015-11-20 to 2017-10-02 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | ||
+ | |[[#Dalteparin_monotherapy_2|Dalteparin]] | ||
+ | | | ||
+ | | style="background-color:#d9ef8b" |Might have lower rates of major bleeding (primary endpoint) | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/NEJMoa1915103 Angelli et al. 2020 (CARAVAGGIO)] | ||
+ | |2017-04 to 2019-06 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | ||
+ | |[[#Dalteparin_monotherapy_2|Dalteparin]] | ||
+ | | style="background-color:#eeee01" |Non-inferior recurrent VTE (primary endpoint) | ||
+ | | style="background-color:#eeee01" |Major bleeding similar in both groups | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
*[[Apixaban (Eliquis)]] 10 mg PO twice per day for 7 days, then 5 mg PO twice per day | *[[Apixaban (Eliquis)]] 10 mg PO twice per day for 7 days, then 5 mg PO twice per day | ||
− | |||
'''6-month course''' | '''6-month course''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''AMPLIFY:''' Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013 Aug 29;369(9):799-808. Epub 2013 Jul 1. [https:// | + | #'''AMPLIFY:''' Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013 Aug 29;369(9):799-808. Epub 2013 Jul 1. [https://doi.org/10.1056/NEJMoa1302507 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23808982/ PubMed] [https://clinicaltrials.gov/study/NCT00643201 NCT00643201] |
+ | #'''ADAM VTE:''' McBane RD 2nd, Wysokinski WE, Le-Rademacher JG, Zemla T, Ashrani A, Tafur A, Perepu U, Anderson D, Gundabolu K, Kuzma C, Perez Botero J, Leon Ferre RA, Henkin S, Lenz CJ, Houghton DE, Vishnu P, Loprinzi CL. Apixaban and dalteparin in active malignancy-associated venous thromboembolism: The ADAM VTE trial. J Thromb Haemost. 2020 Feb;18(2):411-421. Epub 2019 Nov 28. [https://doi.org/10.1111/jth.14662 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31630479/ PubMed] [https://clinicaltrials.gov/study/NCT02585713 NCT02585713] | ||
+ | #'''CARAVAGGIO:''' Agnelli G, Becattini C, Meyer G, Munoz A, Huisman M, Connors J, Cohen A, Bauersachs R, Brenner B, Torbicki A, Sueiro M, Lambert C, Gussoni G, Campanini M, Fontanella A, Vescovo G, Verso M, Caravaggio Investigators. Apixaban for the treatment of venous thromboembolism associated with cancer. N Engl J Med. 2020 Apr 23;382(17):1599-1607. Epub 2020 Mar 29. [https://doi.org/10.1056/NEJMoa1915103 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32223112/ PubMed] [https://clinicaltrials.gov/study/NCT03045406 NCT03045406] | ||
==Argatroban monotherapy {{#subobject:8171b3|Regimen=1}}== | ==Argatroban monotherapy {{#subobject:8171b3|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:3f6d7f|Variant=1}}=== | ===Regimen {{#subobject:3f6d7f|Variant=1}}=== | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
*[[Argatroban (Acova)]] | *[[Argatroban (Acova)]] | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
To be completed | To be completed | ||
− | |||
==Aspirin monotherapy {{#subobject:0481f0|Regimen=1}}== | ==Aspirin monotherapy {{#subobject:0481f0|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:0113df|Variant=1}}=== | ===Regimen {{#subobject:0113df|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !Study | + | !style="width: 17%"|Study |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | !style="width: 15%"|Dates of enrollment |
− | !Comparator | + | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ![[Levels_of_Evidence# | + | !style="width: 17%"|Comparator |
− | ![[Levels_of_Evidence#Toxicity|Toxicity]] | + | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
|- | |- | ||
− | + | |[https://doi.org/10.1056/NEJMoa1700518 Weitz et al. 2017 (EINSTEIN CHOICE)] | |
− | | | + | |2014-03 to 2016-03 |
− | |1. [[#Rivaroxaban_monotherapy_2|Rivaroxaban 10 mg | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | + | |1. [[#Rivaroxaban_monotherapy_2|Rivaroxaban]]; 10 mg/day<br>2. [[#Rivaroxaban_monotherapy_2|Rivaroxaban]]; 20 mg/day | |
− | |||
− | |||
− | |||
| style="background-color:#d73027" |Inferior symptomatic recurrent VTE rate | | style="background-color:#d73027" |Inferior symptomatic recurrent VTE rate | ||
| style="background-color:#ffffbf" |Similar major bleeding | | style="background-color:#ffffbf" |Similar major bleeding | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
*6 to 12 months of a vitamin K antagonist or a direct oral anticoagulant | *6 to 12 months of a vitamin K antagonist or a direct oral anticoagulant | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
− | *[[Aspirin]] 100 mg PO once per day | + | *[[Aspirin]] 100 mg PO once per day |
+ | '''Up to 12-month course''' | ||
+ | </div></div> | ||
− | |||
===References=== | ===References=== | ||
− | # '''EINSTEIN CHOICE:''' Weitz JI, Lensing AWA, Prins MH, Bauersachs R, Beyer-Westendorf J, Bounameaux H, Brighton TA, Cohen AT, Davidson BL, Decousus H, Freitas MCS, Holberg G, Kakkar AK, Haskell L, van Bellen B, Pap AF, Berkowitz SD, Verhamme P, Wells PS, Prandoni P; EINSTEIN CHOICE Investigators. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med. 2017 Mar 30;376(13):1211-1222. Epub 2017 Mar 18. [https:// | + | #'''EINSTEIN CHOICE:''' Weitz JI, Lensing AWA, Prins MH, Bauersachs R, Beyer-Westendorf J, Bounameaux H, Brighton TA, Cohen AT, Davidson BL, Decousus H, Freitas MCS, Holberg G, Kakkar AK, Haskell L, van Bellen B, Pap AF, Berkowitz SD, Verhamme P, Wells PS, Prandoni P; EINSTEIN CHOICE Investigators. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med. 2017 Mar 30;376(13):1211-1222. Epub 2017 Mar 18. [https://doi.org/10.1056/NEJMoa1700518 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28316279/ PubMed] [https://clinicaltrials.gov/study/NCT02064439 NCT02064439] |
− | |||
==Bivalirudin monotherapy {{#subobject:5a08f6|Regimen=1}}== | ==Bivalirudin monotherapy {{#subobject:5a08f6|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:5faf02|Variant=1}}=== | ===Regimen {{#subobject:5faf02|Variant=1}}=== | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
*[[Bivalirudin (Angiomax)]] | *[[Bivalirudin (Angiomax)]] | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
To be completed | To be completed | ||
==Dabigatran monotherapy {{#subobject:4b48cf|Regimen=1}}== | ==Dabigatran monotherapy {{#subobject:4b48cf|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:518855|Variant=1}}=== | ===Regimen {{#subobject:518855|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !Study | + | !style="width: 17%"|Study |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | !style="width: 15%"|Dates of enrollment |
− | !Comparator | + | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ![[Levels_of_Evidence# | + | !style="width: 17%"|Comparator |
− | ![[Levels_of_Evidence#Toxicity|Toxicity]] | + | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | + | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa0906598 Schulman et al. 2009 (RE-COVER)] |
− | | style="background-color:#1a9851" |Phase | + | |2006-04 to 2008-11 |
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
|[[#Warfarin_monotherapy_2|Warfarin]] | |[[#Warfarin_monotherapy_2|Warfarin]] | ||
− | | style="background-color:#eeee01" |Non-inferior composite endpoint | + | | style="background-color:#eeee01" |Non-inferior composite primary endpoint |
| style="background-color:#ffffbf" |Similar major bleeding | | style="background-color:#ffffbf" |Similar major bleeding | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
*[[Dabigatran (Pradaxa)]] 150 mg PO twice per day | *[[Dabigatran (Pradaxa)]] 150 mg PO twice per day | ||
− | |||
'''6-month course''' | '''6-month course''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''RE-COVER:''' Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H, Baanstra D, Schnee J, Goldhaber SZ; RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009 Dec 10;361(24):2342-52. [https:// | + | #'''RE-COVER:''' Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H, Baanstra D, Schnee J, Goldhaber SZ; RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009 Dec 10;361(24):2342-52. [https://doi.org/10.1056/NEJMoa0906598 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19966341/ PubMed] [https://clinicaltrials.gov/study/NCT00291330 NCT00291330] |
− | # '''RE-MEDY:''' Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, Kvamme AM, Friedman J, Mismetti P, Goldhaber SZ; RE-MEDY Trial Investigators; RE-SONATE Trial Investigators. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):709-18. [https:// | + | #'''RE-MEDY:''' Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, Kvamme AM, Friedman J, Mismetti P, Goldhaber SZ; RE-MEDY Trial Investigators; RE-SONATE Trial Investigators. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):709-18. [https://doi.org/10.1056/NEJMoa1113697 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23425163/ PubMed] [https://clinicaltrials.gov/study/NCT00329238 NCT00329238] |
− | # '''RE-COVER II:''' Schulman S, Kakkar AK, Goldhaber SZ, Schellong S, Eriksson H, Mismetti P, Christiansen AV, Friedman J, Le Maulf F, Peter N, Kearon C; RE-COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014 Feb 18;129(7):764-72. Epub 2013 Dec 16. [ | + | #'''RE-COVER II:''' Schulman S, Kakkar AK, Goldhaber SZ, Schellong S, Eriksson H, Mismetti P, Christiansen AV, Friedman J, Le Maulf F, Peter N, Kearon C; RE-COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014 Feb 18;129(7):764-72. Epub 2013 Dec 16. [https://doi.org/10.1161/circulationaha.113.004450 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24344086/ PubMed] [https://clinicaltrials.gov/study/NCT00680186 NCT00680186] |
− | + | #'''DIVERSITY:''' Halton J, Brandão LR, Luciani M, Bomgaars L, Chalmers E, Mitchell LG, Nurmeev I, Sharathkumar A, Svirin P, Gorbatikov K, Tartakovsky I, Simetzberger M, Huang F, Sun Z, Kreuzer J, Gropper S, Reilly P, Brueckmann M, Albisetti M; DIVERSITY Trial Investigators. Dabigatran etexilate for the treatment of acute venous thromboembolism in children (DIVERSITY): a randomised, controlled, open-label, phase 2b/3, non-inferiority trial. Lancet Haematol. 2021 Jan;8(1):e22-e33. Epub 2020 Dec 5. [https://doi.org/10.1016/s2352-3026(20)30368-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33290737/ PubMed] [https://clinicaltrials.gov/study/NCT01895777 NCT01895777] | |
==Dalteparin monotherapy {{#subobject:4a96a1|Regimen=1}}== | ==Dalteparin monotherapy {{#subobject:4a96a1|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:afbbc0|Variant=1}}=== | ===Regimen {{#subobject:afbbc0|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | ! style="width: | + | !style="width: 17%"|Study |
− | ! style="width: | + | !style="width: 15%"|Dates of enrollment |
− | ! style="width: | + | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ! style="width: | + | !style="width: 17%"|Comparator |
− | ! style="width: | + | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1111/jth.12923 Francis et al. 2015 (DALTECAN)] |
+ | |2009-06 to 2011-03 | ||
| style="background-color:#1a9851" |Non-randomized | | style="background-color:#1a9851" |Non-randomized | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
Line 810: | Line 878: | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1200/JCO.2018.78.8034 Young et al. 2018 (SELECT-D)] |
− | | style="background-color:#1a9851" |Phase | + | |2013-09-06 to 2016-12-22 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Rivaroxaban_monotherapy_2|Rivaroxaban]] | ||
+ | | style="background-color:#fc8d59" |Seems to have inferior rate of VTE recurrence | ||
+ | | style="background-color:#1a9850" |Superior rates of clinically relevant non-major bleeding | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/NEJMoa1711948 Raskob et al. 2017 (Hokusai VTE Cancer)] | ||
+ | |2015-07 to 2016-12 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Edoxaban_monotherapy|Edoxaban]] | |[[#Edoxaban_monotherapy|Edoxaban]] | ||
| style="background-color:#eeee01" |Non-inferior composite endpoint of VTE/major bleeding | | style="background-color:#eeee01" |Non-inferior composite endpoint of VTE/major bleeding | ||
| style="background-color:#eeee01" |Non-inferior composite endpoint of VTE/major bleeding | | style="background-color:#eeee01" |Non-inferior composite endpoint of VTE/major bleeding | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1915103 Angelli et al. 2020 (CARAVAGGIO)] |
− | | style="background-color:#1a9851" |Phase | + | |2017-04 to 2019-06 |
− | |[[# | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | | style="background-color:# | + | |[[#Apixaban_monotherapy_3|Apixaban]] |
− | | style="background-color:# | + | | style="background-color:#eeee01" |Non-inferior recurrent VTE |
+ | | style="background-color:#eeee01" |Major bleeding similar in both groups | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
*[[Dalteparin (Fragmin)]] as follows: | *[[Dalteparin (Fragmin)]] as follows: | ||
− | ** | + | **Month 1: 200 IU/kg once per day |
− | ** | + | **Months 2 to 6 up to 12: 150 IU/kg once per day |
+ | '''6- to 12-month course''' | ||
+ | </div></div> | ||
− | |||
===References=== | ===References=== | ||
− | # '''DALTECAN:''' Francis CW, Kessler CM, Goldhaber SZ, Kovacs MJ, Monreal M, Huisman MV, Bergqvist D, Turpie AG, Ortel TL, Spyropoulos AC, Pabinger I, Kakkar AK. Treatment of venous thromboembolism in cancer patients with dalteparin for up to 12 months: the DALTECAN Study. J Thromb Haemost. 2015 Jun;13(6):1028-35. Epub 2015 May 10. [https:// | + | #'''DALTECAN:''' Francis CW, Kessler CM, Goldhaber SZ, Kovacs MJ, Monreal M, Huisman MV, Bergqvist D, Turpie AG, Ortel TL, Spyropoulos AC, Pabinger I, Kakkar AK. Treatment of venous thromboembolism in cancer patients with dalteparin for up to 12 months: the DALTECAN Study. J Thromb Haemost. 2015 Jun;13(6):1028-35. Epub 2015 May 10. [https://doi.org/10.1111/jth.12923 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25827941/ PubMed] [https://clinicaltrials.gov/study/NCT00942968 NCT00942968] |
− | # '''Hokusai VTE Cancer:''' Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia D, Grosso MA, Kakkar AK, Kovacs MJ, Mercuri MF, Meyer G, Segers A, Shi M, Wang TF, Yeo E, Zhang G, Zwicker JI, Weitz JI, Büller HR; Hokusai VTE Cancer Investigators. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med. 2018 Feb 15;378(7):615-624. Epub 2017 Dec 12. [https:// | + | #'''Hokusai VTE Cancer:''' Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia D, Grosso MA, Kakkar AK, Kovacs MJ, Mercuri MF, Meyer G, Segers A, Shi M, Wang TF, Yeo E, Zhang G, Zwicker JI, Weitz JI, Büller HR; Hokusai VTE Cancer Investigators. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med. 2018 Feb 15;378(7):615-624. Epub 2017 Dec 12. [https://doi.org/10.1056/NEJMoa1711948 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/29231094/ PubMed] [https://clinicaltrials.gov/study/NCT02073682 NCT02073682] |
− | # '''SELECT-D:''' Young AM, Marshall A, Thirlwall J, Chapman O, Lokare A, Hill C, Hale D, Dunn JA, Lyman GH, Hutchinson C, MacCallum P, Kakkar A, Hobbs FDR, Petrou S, Dale J, Poole CJ, Maraveyas A, Levine M. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol. 2018 Jul 10;36(20):2017-2023. Epub 2018 May 10. [https:// | + | #'''SELECT-D:''' Young AM, Marshall A, Thirlwall J, Chapman O, Lokare A, Hill C, Hale D, Dunn JA, Lyman GH, Hutchinson C, MacCallum P, Kakkar A, Hobbs FDR, Petrou S, Dale J, Poole CJ, Maraveyas A, Levine M. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol. 2018 Jul 10;36(20):2017-2023. Epub 2018 May 10. [https://doi.org/10.1200/JCO.2018.78.8034 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/29746227/ PubMed] ISRCTN86712308 |
+ | #'''ADAM VTE:''' McBane RD 2nd, Wysokinski WE, Le-Rademacher JG, Zemla T, Ashrani A, Tafur A, Perepu U, Anderson D, Gundabolu K, Kuzma C, Perez Botero J, Leon Ferre RA, Henkin S, Lenz CJ, Houghton DE, Vishnu P, Loprinzi CL. Apixaban and dalteparin in active malignancy-associated venous thromboembolism: The ADAM VTE trial. J Thromb Haemost. 2020 Feb;18(2):411-421. Epub 2019 Nov 28. [https://doi.org/10.1111/jth.14662 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31630479/ PubMed] [https://clinicaltrials.gov/study/NCT02585713 NCT02585713] | ||
+ | #'''CARAVAGGIO:''' Agnelli G, Becattini C, Meyer G, Munoz A, Huisman M, Connors J, Cohen A, Bauersachs R, Brenner B, Torbicki A, Sueiro M, Lambert C, Gussoni G, Campanini M, Fontanella A, Vescovo G, Verso M, Caravaggio Investigators. Apixaban for the treatment of venous thromboembolism associated with cancer. N Engl J Med. 2020 Apr 23;382(17):1599-1607. Epub 2020 Mar 29. [https://doi.org/10.1056/NEJMoa1915103 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32223112/ PubMed] [https://clinicaltrials.gov/study/NCT03045406 NCT03045406] | ||
==Edoxaban monotherapy {{#subobject:d0ebe7|Regimen=1}}== | ==Edoxaban monotherapy {{#subobject:d0ebe7|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen {{#subobject:88a424|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | !style="width: 17%"|Study | |
− | === | + | !style="width: 15%"|Dates of enrollment |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !Study | + | !style="width: 17%"|Comparator |
− | ! | + | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | + | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | |
− | |||
− | ! | ||
− | |||
− | |||
− | |||
− | |[[# | ||
− | |||
− | |||
− | | | ||
− | |||
− | |||
− | |[[# | ||
− | |||
− | |||
|- | |- | ||
− | + | |[https://doi.org/10.1056/NEJMoa1306638 Büller et al. 2013 (Hokusai-VTE)] | |
− | + | |2010-01 to 2012-10 | |
− | + | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic) | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |[https:// | ||
− | | style="background-color:#1a9851" |Phase | ||
|[[#Warfarin_monotherapy_2|Warfarin]] | |[[#Warfarin_monotherapy_2|Warfarin]] | ||
− | | style="background-color:#eeee01" |Non-inferior recurrent VTE rate | + | | style="background-color:#eeee01" |Non-inferior recurrent symptomatic VTE rate (primary endpoint)<br>Symptomatic VTE rate: 3.2% vs 3.5%<br>(HR 0.89, 95% CI 0.70-1.13) |
| style="background-color:#1a9850" |Lower rates of bleeding | | style="background-color:#1a9850" |Lower rates of bleeding | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1711948 Raskob et al. 2017 (Hokusai VTE Cancer)] |
− | | style="background-color:#1a9851" |Phase | + | |2015-07 to 2016-12 |
+ | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic) | ||
|[[#Dalteparin_monotherapy_2|Dalteparin]] | |[[#Dalteparin_monotherapy_2|Dalteparin]] | ||
− | | style="background-color:#eeee01" |Non-inferior composite endpoint of VTE/major bleeding | + | | style="background-color:#eeee01" |Non-inferior composite primary endpoint of VTE/major bleeding |
− | | style="background-color:#eeee01" |Non-inferior composite endpoint of VTE/major bleeding | + | | style="background-color:#eeee01" |Non-inferior composite primary endpoint of VTE/major bleeding |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
*Therapeutic dose [[:Category:Low molecular weight heparins|LMWH]] for at least 5 days, then: | *Therapeutic dose [[:Category:Low molecular weight heparins|LMWH]] for at least 5 days, then: | ||
*[[Edoxaban (Savaysa)]] 60 mg PO once per day | *[[Edoxaban (Savaysa)]] 60 mg PO once per day | ||
− | |||
'''3- to 12-month course''' | '''3- to 12-month course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#fff2ae"> | ||
+ | ====Dose and schedule modifications==== | ||
+ | *[[Edoxaban (Savaysa)]]: Patients with CrCl 30 to 50 mL/min/1.73 m<sup>2</sup>, a body weight of up to 60 kg, or those taking "potent" [[P-glycoprotein_modifying_drugs#P-glycoprotein_inhibitors|P-glycoprotein inhibitors]]: 30 mg PO once per day | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''Hokusai-VTE:''' Büller HR, Décousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, Shi M, Verhamme P, Wells P; Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013 Oct 10;369(15):1406-15. Epub 2013 Aug 31. Erratum in: N Engl J Med. 2014 Jan 23;370(4):390. [https:// | + | #'''Hokusai-VTE:''' Büller HR, Décousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, Shi M, Verhamme P, Wells P; Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013 Oct 10;369(15):1406-15. Epub 2013 Aug 31. Erratum in: N Engl J Med. 2014 Jan 23;370(4):390. [https://doi.org/10.1056/NEJMoa1306638 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23991658/ PubMed] [https://clinicaltrials.gov/study/NCT00986154 NCT00986154] |
− | ## '''Subgroup analysis:''' Raskob GE, van Es N, Segers A, Angchaisuksiri P, Oh D, Boda Z, Lyons RM, Meijer K, Gudz I, Weitz JI, Zhang G, Lanz H, Mercuri MF, Büller HR; Hokusai-VTE investigators. Edoxaban for venous thromboembolism in patients with cancer: results from a non-inferiority subgroup analysis of the Hokusai-VTE randomised, double-blind, double-dummy trial. Lancet Haematol. 2016 Aug;3(8):e379-87. Epub 2016 Jul 1. [https:// | + | ##'''Subgroup analysis:''' Raskob GE, van Es N, Segers A, Angchaisuksiri P, Oh D, Boda Z, Lyons RM, Meijer K, Gudz I, Weitz JI, Zhang G, Lanz H, Mercuri MF, Büller HR; Hokusai-VTE investigators. Edoxaban for venous thromboembolism in patients with cancer: results from a non-inferiority subgroup analysis of the Hokusai-VTE randomised, double-blind, double-dummy trial. Lancet Haematol. 2016 Aug;3(8):e379-87. Epub 2016 Jul 1. [https://doi.org/10.1016/S2352-3026(16)30057-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27476789/ PubMed] |
− | # '''Hokusai VTE Cancer:''' Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia D, Grosso MA, Kakkar AK, Kovacs MJ, Mercuri MF, Meyer G, Segers A, Shi M, Wang TF, Yeo E, Zhang G, Zwicker JI, Weitz JI, Büller HR; Hokusai VTE Cancer Investigators. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med. 2018 Feb 15;378(7):615-624. Epub 2017 Dec 12. [https:// | + | #'''Hokusai VTE Cancer:''' Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia D, Grosso MA, Kakkar AK, Kovacs MJ, Mercuri MF, Meyer G, Segers A, Shi M, Wang TF, Yeo E, Zhang G, Zwicker JI, Weitz JI, Büller HR; Hokusai VTE Cancer Investigators. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med. 2018 Feb 15;378(7):615-624. Epub 2017 Dec 12. [https://doi.org/10.1056/NEJMoa1711948 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/29231094/ PubMed] [https://clinicaltrials.gov/study/NCT02073682 NCT02073682] |
==Enoxaparin monotherapy {{#subobject:fc9e30|Regimen=1}}== | ==Enoxaparin monotherapy {{#subobject:fc9e30|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:5a4974|Variant=1}}=== | ===Regimen {{#subobject:5a4974|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | ! style="width: | + | !style="width: 20%"|Study |
− | ! style="width: | + | !style="width: 20%"|Dates of enrollment |
− | ! style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ! style="width: | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1001/jama.296.8.935 Kearon et al. 2006 (FIDO)] |
− | | style="background-color:#1a9851" |Phase | + | |1998-09 to 2004-02 |
− | |1. [[#Dalteparin_monotherapy_2|Dalteparin]]<br> 2. [[#Heparin_monotherapy| | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
+ | |1. [[#Dalteparin_monotherapy_2|Dalteparin]]<br>2. [[#Heparin_monotherapy|UFH]] | ||
| style="background-color:#eeee01" |No difference in recurrent VTE or major bleeding | | style="background-color:#eeee01" |No difference in recurrent VTE or major bleeding | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Anticoagulation==== | ====Anticoagulation==== | ||
− | *[[Enoxaparin (Lovenox)]] | + | *[[Enoxaparin (Lovenox)]] 100 IU/kg SC once every 12 hours |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''FIDO:''' Kearon C, Ginsberg JS, Julian JA, Douketis J, Solymoss S, Ockelford P, Jackson S, Turpie AG, MacKinnon B, Hirsh J, Gent M; Fixed-Dose Heparin (FIDO) Investigators. Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism. JAMA. 2006 | + | #'''FIDO:''' Kearon C, Ginsberg JS, Julian JA, Douketis J, Solymoss S, Ockelford P, Jackson S, Turpie AG, MacKinnon B, Hirsh J, Gent M; Fixed-Dose Heparin (FIDO) Investigators. Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism. JAMA. 2006 Aug 23;296(8):935-42. [https://doi.org/10.1001/jama.296.8.935 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16926353/ PubMed] [https://clinicaltrials.gov/study/NCT00182403 NCT00182403] |
− | |||
==Fondaparinux monotherapy {{#subobject:7a8cb8|Regimen=1}}== | ==Fondaparinux monotherapy {{#subobject:7a8cb8|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:ab5c25|Variant=1}}=== | ===Regimen {{#subobject:ab5c25|Variant=1}}=== | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
*[[Fondaparinux (Arixtra)]] | *[[Fondaparinux (Arixtra)]] | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
To be completed | To be completed | ||
− | |||
==Heparin monotherapy {{#subobject:2a8be8|Regimen=1}}== | ==Heparin monotherapy {{#subobject:2a8be8|Regimen=1}}== | ||
− | + | UFH: '''<u>U</u>'''n'''<u>F</u>'''ractionated '''<u>H</u>'''eparin | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
===Regimen {{#subobject:8cae03|Variant=1}}=== | ===Regimen {{#subobject:8cae03|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | ! style="width: | + | !style="width: 20%"|Study |
− | ! style="width: | + | !style="width: 20%"|Dates of enrollment |
− | ! style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ! style="width: | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1001/jama.1947.02880170009003 Loewe & Hirsch 1947] |
− | |Observational | + | |Not reported |
+ | | style="background-color:#ffffbe" |Observational | ||
|None | |None | ||
|2.4% fatality rate due to pulmonary embolism | |2.4% fatality rate due to pulmonary embolism | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1001/jama.296.8.935 Kearon et al. 2006 (FIDO)] |
− | | style="background-color:#1a9851" |Phase | + | |1998-09 to 2004-02 |
− | |1. [[#Dalteparin_monotherapy_2|Dalteparin]]<br> 2. [[#Enoxaparin_monotherapy_3|Enoxaparin]] | + | | style="background-color:#1a9851" |Phase 3 (C) |
+ | |1. [[#Dalteparin_monotherapy_2|Dalteparin]]<br>2. [[#Enoxaparin_monotherapy_3|Enoxaparin]] | ||
| style="background-color:#eeee01" |No difference in recurrent VTE or major bleeding | | style="background-color:#eeee01" |No difference in recurrent VTE or major bleeding | ||
|} | |} | ||
''Note: In Loewe and Hirsch, heparin was administered as a deep subcutaneous injection (200 to 400 mg / 200,000 to 400,000 IU) in Pitkin menstruum every two to three days for 10 to 14 days for deep vein thrombosis and extended for one to two additional weeks for pulmonary embolism.'' | ''Note: In Loewe and Hirsch, heparin was administered as a deep subcutaneous injection (200 to 400 mg / 200,000 to 400,000 IU) in Pitkin menstruum every two to three days for 10 to 14 days for deep vein thrombosis and extended for one to two additional weeks for pulmonary embolism.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
− | *[[Unfractionated heparin (UFH)]] | + | *[[Unfractionated heparin (UFH)]] 333 units/kg SC once, then 250 units/kg SC every 12 hours |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Loewe L, Hirsch E. Heparin in the treatment of thromboembolic disease. JAMA. 1947;133(17):1263-1268. [https:// | + | #Loewe L, Hirsch E. Heparin in the treatment of thromboembolic disease. JAMA. 1947;133(17):1263-1268. [https://doi.org/10.1001/jama.1947.02880170009003 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20293012/ PubMed] |
− | # '''FIDO:''' Kearon C, Ginsberg JS, Julian JA, Douketis J, Solymoss S, Ockelford P, Jackson S, Turpie AG, MacKinnon B, Hirsh J, Gent M; Fixed-Dose Heparin (FIDO) Investigators. Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism. JAMA. 2006 | + | #'''FIDO:''' Kearon C, Ginsberg JS, Julian JA, Douketis J, Solymoss S, Ockelford P, Jackson S, Turpie AG, MacKinnon B, Hirsh J, Gent M; Fixed-Dose Heparin (FIDO) Investigators. Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism. JAMA. 2006 Aug 23;296(8):935-42. [https://doi.org/10.1001/jama.296.8.935 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16926353/ PubMed] [https://clinicaltrials.gov/study/NCT00182403 NCT00182403] |
− | |||
==Lepirudin monotherapy {{#subobject:b61e00|Regimen=1}}== | ==Lepirudin monotherapy {{#subobject:b61e00|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:22918f|Variant=1}}=== | ===Regimen {{#subobject:22918f|Variant=1}}=== | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
*[[Lepirudin (Refludan)]] | *[[Lepirudin (Refludan)]] | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
To be completed | To be completed | ||
− | |||
==Rivaroxaban monotherapy {{#subobject:f435a7|Regimen=1}}== | ==Rivaroxaban monotherapy {{#subobject:f435a7|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #1, 10 mg/day {{#subobject:4f1fdf|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | !style="width: 17%"|Study | |
− | === | + | !style="width: 15%"|Dates of enrollment |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !Study | + | !style="width: 17%"|Comparator |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | !Comparator | + | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] |
− | ![[Levels_of_Evidence# | ||
− | ![[Levels_of_Evidence#Toxicity|Toxicity]] | ||
|- | |- | ||
− | | rowspan="2" |[https:// | + | | rowspan="2" |[https://doi.org/10.1056/NEJMoa1700518 Weitz et al. 2017 (EINSTEIN CHOICE)] |
− | | rowspan="2" style="background-color:#1a9851" |Phase | + | |rowspan=2|2014-03 to 2016-03 |
+ | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc) | ||
|1. [[#Aspirin_monotherapy_2|Aspirin]] | |1. [[#Aspirin_monotherapy_2|Aspirin]] | ||
− | | style="background-color:#1a9850" |Superior symptomatic recurrent VTE rate | + | | style="background-color:#1a9850" |Superior symptomatic recurrent VTE rate (primary endpoint) |
| style="background-color:#ffffbf" |Similar major bleeding | | style="background-color:#ffffbf" |Similar major bleeding | ||
|- | |- | ||
− | |2. Rivaroxaban 20 mg | + | |2. [[#Rivaroxaban_monotherapy_2|Rivaroxaban]]; 20 mg/day |
− | | style="background-color:#ffffbf" | | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of symptomatic recurrent VTE rate |
| style="background-color:#ffffbf" |Similar major bleeding | | style="background-color:#ffffbf" |Similar major bleeding | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
*6 to 12 months of a vitamin K antagonist or a direct oral anticoagulant | *6 to 12 months of a vitamin K antagonist or a direct oral anticoagulant | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
*[[Rivaroxaban (Xarelto)]] 10 mg PO once per day | *[[Rivaroxaban (Xarelto)]] 10 mg PO once per day | ||
− | |||
'''Up to 12-month course''' | '''Up to 12-month course''' | ||
− | + | </div></div><br> | |
− | === | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | ===Regimen variant #2, 20 mg/day {{#subobject:ba11d9|Variant=1}}=== |
− | !Study | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | !style="width: 17%"|Study |
− | !Comparator | + | !style="width: 15%"|Dates of enrollment |
− | ![[Levels_of_Evidence# | + | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ![[Levels_of_Evidence#Toxicity|Toxicity]] | + | !style="width: 17%"|Comparator |
+ | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
|- | |- | ||
− | | rowspan="2" |[https:// | + | | rowspan="2" |[https://doi.org/10.1056/NEJMoa1700518 Weitz et al. 2017 (EINSTEIN CHOICE)] |
− | | rowspan="2" style="background-color:#1a9851" |Phase | + | |rowspan=2|2014-03 to 2016-03 |
+ | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc) | ||
|1. [[#Aspirin_monotherapy_2|Aspirin]] | |1. [[#Aspirin_monotherapy_2|Aspirin]] | ||
− | | style="background-color:#1a9850" |Superior symptomatic recurrent VTE rate | + | | style="background-color:#1a9850" |Superior symptomatic recurrent VTE rate (primary endpoint) |
| style="background-color:#ffffbf" |Similar major bleeding | | style="background-color:#ffffbf" |Similar major bleeding | ||
|- | |- | ||
− | |2. Rivaroxaban 10 mg | + | |2. [[#Rivaroxaban_monotherapy_2|Rivaroxaban]]; 10 mg/day |
− | | style="background-color:#ffffbf" | | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of symptomatic recurrent VTE rate |
| style="background-color:#ffffbf" |Similar major bleeding | | style="background-color:#ffffbf" |Similar major bleeding | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
*6 to 12 months of a vitamin K antagonist or a direct oral anticoagulant | *6 to 12 months of a vitamin K antagonist or a direct oral anticoagulant | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
*[[Rivaroxaban (Xarelto)]] 20 mg PO once per day | *[[Rivaroxaban (Xarelto)]] 20 mg PO once per day | ||
− | |||
'''Up to 12-month course''' | '''Up to 12-month course''' | ||
− | + | </div></div><br> | |
− | === | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | ===Regimen variant #3, 20 mg/day with loading dose {{#subobject:ba11d9|Variant=1}}=== |
− | !Study | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | !style="width: 17%"|Study |
− | !Comparator | + | !style="width: 15%"|Dates of enrollment |
− | ![[Levels_of_Evidence# | + | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ![[Levels_of_Evidence#Toxicity|Toxicity]] | + | !style="width: 17%"|Comparator |
+ | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1007903 Bauersachs et al. 2010 (EINSTEIN Acute DVT)] |
− | | style="background-color:#1a9851" |Phase | + | |2007-03 to 2009-09 |
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
|[[#Warfarin_monotherapy_2|Warfarin]] | |[[#Warfarin_monotherapy_2|Warfarin]] | ||
− | | style="background-color:#eeee01" |Non-inferior VTE recurrence | + | | style="background-color:#eeee01" |Non-inferior VTE recurrence (primary endpoint) |
| style="background-color:#ffffbf" |Similar major bleeding | | style="background-color:#ffffbf" |Similar major bleeding | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1113572 Büller et al. 2012 (EINSTEIN-PE)] |
− | | style="background-color:#1a9851" |Phase | + | |2007-03 to 2011-03 |
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
|[[#Warfarin_monotherapy_2|Warfarin]] | |[[#Warfarin_monotherapy_2|Warfarin]] | ||
− | | style="background-color:#eeee01" |Non-inferior symptomatic VTE recurrence | + | | style="background-color:#eeee01" |Non-inferior symptomatic VTE recurrence (primary endpoint) |
| style="background-color:#ffffbf" |Similar major bleeding | | style="background-color:#ffffbf" |Similar major bleeding | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1200/JCO.2018.78.8034 Young et al. 2018 (SELECT-D)] |
− | | style="background-color:#1a9851" |Phase | + | |2013-09-06 to 2016-12-22 |
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
|[[#Dalteparin_monotherapy_2|Dalteparin]] | |[[#Dalteparin_monotherapy_2|Dalteparin]] | ||
− | | style="background-color:#91cf60" |Seems to have superior rate of VTE recurrence | + | | style="background-color:#91cf60" |Seems to have superior rate of VTE recurrence over 6 months (primary endpoint) |
| style="background-color:#d73027" |Inferior rates of clinically relevant non-major bleeding | | style="background-color:#d73027" |Inferior rates of clinically relevant non-major bleeding | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
*[[Rivaroxaban (Xarelto)]] 15 mg PO twice per day for 3 weeks, then 20 mg PO once per day | *[[Rivaroxaban (Xarelto)]] 15 mg PO twice per day for 3 weeks, then 20 mg PO once per day | ||
− | |||
'''3-, 6-, or 12-month course''' | '''3-, 6-, or 12-month course''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''EINSTEIN Acute DVT:''' Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, Gallus AS, Lensing AW, Misselwitz F, Prins MH, Raskob GE, Segers A, Verhamme P, Wells P, Agnelli G, Bounameaux H, Cohen A, Davidson BL, Piovella F, Schellong S; EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010 Dec 23;363(26):2499-510. Epub 2010 Dec 3. [https:// | + | #'''EINSTEIN Acute DVT:''' Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, Gallus AS, Lensing AW, Misselwitz F, Prins MH, Raskob GE, Segers A, Verhamme P, Wells P, Agnelli G, Bounameaux H, Cohen A, Davidson BL, Piovella F, Schellong S; EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010 Dec 23;363(26):2499-510. Epub 2010 Dec 3. [https://doi.org/10.1056/NEJMoa1007903 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21128814/ PubMed] [https://clinicaltrials.gov/study/NCT00440193 NCT00440193]; [https://clinicaltrials.gov/study/NCT00439725 NCT00439725] |
− | # '''EINSTEIN-PE:''' Büller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A; | + | #'''EINSTEIN-PE:''' Büller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A; EINSTEIN-PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012 Apr 5;366(14):1287-97. Epub 2012 Mar 26. [https://doi.org/10.1056/NEJMoa1113572 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22449293/ PubMed] [https://clinicaltrials.gov/study/NCT00439777 NCT00439777] |
− | # '''XALIA:''' Ageno W, Mantovani LG, Haas S, Kreutz R, Monje D, Schneider J, van Eickels M, Gebel M, Zell E, Turpie AG. Safety and effectiveness of oral rivaroxaban versus standard anticoagulation for the treatment of symptomatic deep-vein thrombosis (XALIA): an international, prospective, non-interventional study. Lancet Haematol. 2016 Jan;3(1):e12-21. Epub 2015 Dec 8. [https:// | + | #'''XALIA:''' Ageno W, Mantovani LG, Haas S, Kreutz R, Monje D, Schneider J, van Eickels M, Gebel M, Zell E, Turpie AG. Safety and effectiveness of oral rivaroxaban versus standard anticoagulation for the treatment of symptomatic deep-vein thrombosis (XALIA): an international, prospective, non-interventional study. Lancet Haematol. 2016 Jan;3(1):e12-21. Epub 2015 Dec 8. [https://doi.org/10.1016/S2352-3026%2815)00257-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26765643/ PubMed] [https://clinicaltrials.gov/study/NCT01619007 NCT01619007] |
− | # '''EINSTEIN CHOICE:''' Weitz JI, Lensing AWA, Prins MH, Bauersachs R, Beyer-Westendorf J, Bounameaux H, Brighton TA, Cohen AT, Davidson BL, Decousus H, Freitas MCS, Holberg G, Kakkar AK, Haskell L, van Bellen B, Pap AF, Berkowitz SD, Verhamme P, Wells PS, Prandoni P; EINSTEIN CHOICE Investigators. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med. 2017 Mar 30;376(13):1211-1222. Epub 2017 Mar 18. [https:// | + | #'''EINSTEIN CHOICE:''' Weitz JI, Lensing AWA, Prins MH, Bauersachs R, Beyer-Westendorf J, Bounameaux H, Brighton TA, Cohen AT, Davidson BL, Decousus H, Freitas MCS, Holberg G, Kakkar AK, Haskell L, van Bellen B, Pap AF, Berkowitz SD, Verhamme P, Wells PS, Prandoni P; EINSTEIN CHOICE Investigators. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med. 2017 Mar 30;376(13):1211-1222. Epub 2017 Mar 18. [https://doi.org/10.1056/NEJMoa1700518 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28316279/ PubMed] [https://clinicaltrials.gov/study/NCT02064439 NCT02064439] |
− | # '''SELECT-D:''' Young AM, Marshall A, Thirlwall J, Chapman O, Lokare A, Hill C, Hale D, Dunn JA, Lyman GH, Hutchinson C, MacCallum P, Kakkar A, Hobbs FDR, Petrou S, Dale J, Poole CJ, Maraveyas A, Levine M. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol. 2018 Jul 10;36(20):2017-2023. Epub 2018 May 10. [https:// | + | #'''SELECT-D:''' Young AM, Marshall A, Thirlwall J, Chapman O, Lokare A, Hill C, Hale D, Dunn JA, Lyman GH, Hutchinson C, MacCallum P, Kakkar A, Hobbs FDR, Petrou S, Dale J, Poole CJ, Maraveyas A, Levine M. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol. 2018 Jul 10;36(20):2017-2023. Epub 2018 May 10. [https://doi.org/10.1200/JCO.2018.78.8034 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/29746227/ PubMed] ISRCTN86712308 |
− | + | #'''EINSTEIN Junior:''' Male C, Lensing AWA, Palumbo JS, Kumar R, Nurmeev I, Hege K, Bonnet D, Connor P, Hooimeijer HL, Torres M, Chan AKC, Kenet G, Holzhauer S, Santamaría A, Amedro P, Chalmers E, Simioni P, Bhat RV, Yee DL, Lvova O, Beyer-Westendorf J, Biss TT, Martinelli I, Saracco P, Peters M, Kállay K, Gauger CA, Massicotte MP, Young G, Pap AF, Majumder M, Smith WT, Heubach JF, Berkowitz SD, Thelen K, Kubitza D, Crowther M, Prins MH, Monagle P; EINSTEIN-Jr Phase 3 Investigators. Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial. Lancet Haematol. 2020 Jan;7(1):e18-e27. Epub 2019 Nov 5. [https://doi.org/10.1016/s2352-3026(19)30219-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31699660/ PubMed] [https://clinicaltrials.gov/study/NCT02234843 NCT02234843] | |
==Tinzaparin monotherapy {{#subobject:3d9d84|Regimen=1}}== | ==Tinzaparin monotherapy {{#subobject:3d9d84|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:24b40c|Variant=1}}=== | ===Regimen {{#subobject:24b40c|Variant=1}}=== | ||
''Note: this agent has been withdrawn from the US market.'' | ''Note: this agent has been withdrawn from the US market.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
*[[Tinzaparin (Innohep)]] | *[[Tinzaparin (Innohep)]] | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''LITE:''' Hull RD, Pineo GF, Brant RF, Mah AF, Burke N, Dear R, Wong T, Cook R, Solymoss S, Poon MC, Raskob G; LITE Trial Investigators. Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer. Am J Med. 2006 Dec;119(12):1062-72. [https:// | + | #'''LITE:''' Hull RD, Pineo GF, Brant RF, Mah AF, Burke N, Dear R, Wong T, Cook R, Solymoss S, Poon MC, Raskob G; LITE Trial Investigators. Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer. Am J Med. 2006 Dec;119(12):1062-72. [https://doi.org/10.1016/j.amjmed.2006.02.022 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17145251/ PubMed] |
− | # '''CATCH:''' Lee AY, Kamphuisen PW, Meyer G, Bauersachs R, Janas MS, Jarner MF, Khorana AA; CATCH Investigators. Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: A randomized clinical trial. JAMA. 2015 Aug 18;314(7):677-86. [ | + | #'''CATCH:''' Lee AY, Kamphuisen PW, Meyer G, Bauersachs R, Janas MS, Jarner MF, Khorana AA; CATCH Investigators. Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: A randomized clinical trial. JAMA. 2015 Aug 18;314(7):677-86. [https://doi.org/10.1001/jama.2015.9243 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26284719/ PubMed] [https://clinicaltrials.gov/study/NCT01130025 NCT01130025] |
− | |||
==Warfarin monotherapy {{#subobject:76610c|Regimen=1}}== | ==Warfarin monotherapy {{#subobject:76610c|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:cd707c|Variant=1}}=== | ===Regimen {{#subobject:cd707c|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !Study | + | !style="width: 17%"|Study |
− | ![[Levels_of_Evidence#Evidence|Evidence]] | + | !style="width: 15%"|Dates of enrollment |
− | !Comparator | + | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ![[Levels_of_Evidence# | + | !style="width: 17%"|Comparator |
− | ![[Levels_of_Evidence#Toxicity|Toxicity]] | + | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa0906598 Schulman et al. 2009 (RE-COVER)] |
− | | style="background-color:#1a9851" |Phase | + | |2006-04 to 2008-11 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Dabigatran_monotherapy|Dabigatran]] | |[[#Dabigatran_monotherapy|Dabigatran]] | ||
| style="background-color:#eeee01" |Non-inferior composite endpoint | | style="background-color:#eeee01" |Non-inferior composite endpoint | ||
| style="background-color:#ffffbf" |Similar major bleeding | | style="background-color:#ffffbf" |Similar major bleeding | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1007903 Bauersachs et al. 2010 (EINSTEIN Acute DVT)] |
− | | style="background-color:#1a9851" |Phase | + | |2007-03 to 2009-09 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Rivaroxaban_monotherapy_2|Rivaroxaban]] | |[[#Rivaroxaban_monotherapy_2|Rivaroxaban]] | ||
| style="background-color:#eeee01" |Non-inferior VTE recurrence | | style="background-color:#eeee01" |Non-inferior VTE recurrence | ||
| style="background-color:#ffffbf" |Similar major bleeding | | style="background-color:#ffffbf" |Similar major bleeding | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1113572 Büller et al. 2012 (EINSTEIN-PE)] |
− | | style="background-color:#1a9851" |Phase | + | |2007-03 to 2011-03 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Rivaroxaban_monotherapy_2|Rivaroxaban]] | |[[#Rivaroxaban_monotherapy_2|Rivaroxaban]] | ||
− | | style="background-color:#eeee01" |Non-inferior VTE recurrence | + | | style="background-color:#eeee01" |Non-inferior symptomatic VTE recurrence (primary endpoint) |
| style="background-color:#ffffbf" |Similar major bleeding | | style="background-color:#ffffbf" |Similar major bleeding | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1302507 Agnelli et al. 2013 (AMPLIFY)] |
− | | style="background-color:#1a9851" |Phase | + | |2008-08 to 2012-08 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Apixaban_monotherapy_3|Apixaban]] | |[[#Apixaban_monotherapy_3|Apixaban]] | ||
− | | style="background-color:#eeee01" |Non-inferior composite endpoint | + | | style="background-color:#eeee01" |Non-inferior composite primary endpoint |
| style="background-color:#d73027" |Higher rates of bleeding | | style="background-color:#d73027" |Higher rates of bleeding | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1306638 Büller et al. 2013 (Hokusai-VTE)] |
− | | style="background-color:#1a9851" |Phase | + | |2010-01 to 2012-10 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Edoxaban_monotherapy|Edoxaban]] | |[[#Edoxaban_monotherapy|Edoxaban]] | ||
| style="background-color:#eeee01" |Non-inferior recurrent VTE rate | | style="background-color:#eeee01" |Non-inferior recurrent VTE rate | ||
| style="background-color:#d73027" |Higher rates of bleeding | | style="background-color:#d73027" |Higher rates of bleeding | ||
+ | |- | ||
+ | |[https://doi.org/10.1001/jama.2015.9243 Lee et al. 2015 (CATCH)] | ||
+ | |2010-08 to 2013-11 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Tinzaparin_monotherapy|Tinzaparin]] | ||
+ | | style="background-color:#fee08b" |Might have inferior composite outcome | ||
+ | | style="background-color:#ffffbf" |Similar major bleeding | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
− | *[[Warfarin (Coumadin)]] with goal INR between 2 | + | *[[Warfarin (Coumadin)]] with goal INR between 2 and 3.0 |
− | ====Supportive | + | ====Supportive therapy==== |
− | *Most protocols: [[Enoxaparin (Lovenox)]] 1 mg/kg SC every 12 hours until INR greater than 2.0 | + | *Most protocols: [[Enoxaparin (Lovenox)]] 1 mg/kg SC once every 12 hours, given until INR greater than 2.0 |
− | |||
'''3-, 6-, or 12- month course (see individual papers)''' | '''3-, 6-, or 12- month course (see individual papers)''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | #Schulman S, Rhedin AS, Lindmarker P, Carlsson A, Lärfars G, Nicol P, Loogna E, Svensson E, Ljungberg B, Walter H; Duration of Anticoagulation Trial Study Group. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. N Engl J Med. 1995 Jun 22;332(25):1661-5. [https://doi.org/10.1056/nejm199506223322501 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7760866/ PubMed] |
− | # | + | #Schulman S, Granqvist S, Holmström M, Carlsson A, Lindmarker P, Nicol P, Eklund SG, Nordlander S, Lärfars G, Leijd B, Linder O, Loogna E; The Duration of Anticoagulation Trial Study Group. The duration of oral anticoagulant therapy after a second episode of venous thromboembolism. N Engl J Med. 1997 Feb 6;336(6):393-8. [https://doi.org/10.1056/nejm199702063360601 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9010144/ PubMed] |
− | # | + | #Kearon C, Gent M, Hirsh J, Weitz J, Kovacs MJ, Anderson DR, Turpie AG, Green D, Ginsberg JS, Wells P, MacKinnon B, Julian JA. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med. 1999 Mar 25;340(12):901-7. Erratum in: N Engl J Med 1999 Jul 22;341(4):298. [https://doi.org/10.1056/nejm199903253401201 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10089183/ PubMed] |
− | # | + | #Agnelli G, Prandoni P, Santamaria MG, Bagatella P, Iorio A, Bazzan M, Moia M, Guazzaloca G, Bertoldi A, Tomasi C, Scannapieco G, Ageno W; Warfarin Optimal Duration Italian Trial Investigators. Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis. Warfarin Optimal Duration Italian Trial Investigators. N Engl J Med. 2001 Jul 19;345(3):165-9. [https://doi.org/10.1056/nejm200107193450302 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11463010/ PubMed] |
− | # ''' | + | #'''DOTAVK:''' Pinede L, Ninet J, Duhaut P, Chabaud S, Demolombe-Rague S, Durieu I, Nony P, Sanson C, Boissel JP; Investigators of the "Durée Optimale du Traitement AntiVitamines K" (DOTAVK) Study. Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep vein thrombosis or pulmonary embolism and comparison of 6 and 12 weeks of therapy after isolated calf deep vein thrombosis. Circulation. 2001 May 22;103(20):2453-60. [https://doi.org/10.1161/01.cir.103.20.2453 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11369685/ PubMed] |
− | # | + | #Agnelli G, Prandoni P, Becattini C, Silingardi M, Taliani MR, Miccio M, Imberti D, Poggio R, Ageno W, Pogliani E, Porro F, Zonzin P; Warfarin Optimal Duration Italian Trial Investigators. Extended oral anticoagulant therapy after a first episode of pulmonary embolism. Ann Intern Med. 2003 Jul 1;139(1):19-25. [https://doi.org/10.7326/0003-4819-139-1-200307010-00008 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12834314/ PubMed] |
− | # ''' | + | #'''SOFAST:''' Kearon C, Ginsberg JS, Anderson DR, Kovacs MJ, Wells P, Julian JA, Mackinnon B, Demers C, Douketis J, Turpie AG, Van Nguyen P, Green D, Kassis J, Kahn SR, Solymoss S, Desjardins L, Geerts W, Johnston M, Weitz JI, Hirsh J, Gent M; SOFAST Investigators. Comparison of 1 month with 3 months of anticoagulation for a first episode of venous thromboembolism associated with a transient risk factor. J Thromb Haemost. 2004 May;2(5):743-9. [https://doi.org/10.1046/j.1538-7836.2004.00698.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/15099280/ PubMed] |
− | + | #'''LITE:''' Hull RD, Pineo GF, Brant RF, Mah AF, Burke N, Dear R, Wong T, Cook R, Solymoss S, Poon MC, Raskob G; LITE Trial Investigators. Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer. Am J Med. 2006 Dec;119(12):1062-72. [https://doi.org/10.1016/j.amjmed.2006.02.022 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17145251/ PubMed] | |
− | # '''RE-COVER | + | #'''RE-COVER:''' Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H, Baanstra D, Schnee J, Goldhaber SZ; RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009 Dec 10;361(24):2342-52. [https://doi.org/10.1056/NEJMoa0906598 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19966341/ PubMed] [https://clinicaltrials.gov/study/NCT00291330 NCT00291330] |
− | # ''' | + | #'''EINSTEIN Acute DVT:''' Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, Gallus AS, Lensing AW, Misselwitz F, Prins MH, Raskob GE, Segers A, Verhamme P, Wells P, Agnelli G, Bounameaux H, Cohen A, Davidson BL, Piovella F, Schellong S; EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010 Dec 23;363(26):2499-510. Epub 2010 Dec 3. [https://doi.org/10.1056/NEJMoa1007903 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21128814/ PubMed] [https://clinicaltrials.gov/study/NCT00440193 NCT00440193]; [https://clinicaltrials.gov/study/NCT00439725 NCT00439725] |
+ | #'''EINSTEIN-PE:''' Büller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A; EINSTEIN-PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012 Apr 5;366(14):1287-97. Epub 2012 Mar 26. [https://doi.org/10.1056/NEJMoa1113572 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22449293/ PubMed] [https://clinicaltrials.gov/study/NCT00439777 NCT00439777] | ||
+ | #'''RE-MEDY:''' Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, Kvamme AM, Friedman J, Mismetti P, Goldhaber SZ; RE-MEDY Trial Investigators; RE-SONATE Trial Investigators. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):709-18. [https://doi.org/10.1056/NEJMoa1113697 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23425163/ PubMed] [https://clinicaltrials.gov/study/NCT00329238 NCT00329238] | ||
+ | #'''AMPLIFY:''' Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013 Aug 29;369(9):799-808. Epub 2013 Jul 1. [https://doi.org/10.1056/NEJMoa1302507 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23808982/ PubMed] [https://clinicaltrials.gov/study/NCT00643201 NCT00643201] | ||
+ | #'''Hokusai-VTE:''' Büller HR, Décousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, Shi M, Verhamme P, Wells P; Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013 Oct 10;369(15):1406-15. Epub 2013 Aug 31. Erratum in: N Engl J Med. 2014 Jan 23;370(4):390. [https://doi.org/10.1056/NEJMoa1306638 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23991658/ PubMed] [https://clinicaltrials.gov/study/NCT00986154 NCT00986154] | ||
+ | ##'''Subgroup analysis:''' Raskob GE, van Es N, Segers A, Angchaisuksiri P, Oh D, Boda Z, Lyons RM, Meijer K, Gudz I, Weitz JI, Zhang G, Lanz H, Mercuri MF, Büller HR; Hokusai-VTE investigators. Edoxaban for venous thromboembolism in patients with cancer: results from a non-inferiority subgroup analysis of the Hokusai-VTE randomised, double-blind, double-dummy trial. Lancet Haematol. 2016 Aug;3(8):e379-87. Epub 2016 Jul 1. [https://doi.org/10.1016/S2352-3026(16)30057-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27476789/ PubMed] | ||
+ | #'''RE-COVER II:''' Schulman S, Kakkar AK, Goldhaber SZ, Schellong S, Eriksson H, Mismetti P, Christiansen AV, Friedman J, Le Maulf F, Peter N, Kearon C; RE-COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014 Feb 18;129(7):764-72. Epub 2013 Dec 16. [https://doi.org/10.1161/circulationaha.113.004450 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24344086/ PubMed] [https://clinicaltrials.gov/study/NCT00680186 NCT00680186] | ||
+ | #'''CATCH:''' Lee AY, Kamphuisen PW, Meyer G, Bauersachs R, Janas MS, Jarner MF, Khorana AA; CATCH Investigators. Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: A randomized clinical trial. JAMA. 2015 Aug 18;314(7):677-86. [https://doi.org/10.1001/jama.2015.9243 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26284719/ PubMed] [https://clinicaltrials.gov/study/NCT01130025 NCT01130025] | ||
=Additional information= | =Additional information= | ||
Line 1,149: | Line 1,231: | ||
**[http://journal.publications.chestnet.org/article.aspx?articleID=1159399 Executive summary] [http://journal.publications.chestnet.org/data/Journals/CHEST/23443/chest_141_2_suppl_7S.pdf PDF] | **[http://journal.publications.chestnet.org/article.aspx?articleID=1159399 Executive summary] [http://journal.publications.chestnet.org/data/Journals/CHEST/23443/chest_141_2_suppl_7S.pdf PDF] | ||
*Bleeding risk on anticoagulation: [http://www.globalrph.com/has-bled-score.htm HAS-BLED]; [http://www.globalrph.com/hemorr2hages-bleeding-risk.htm HEMORR2HAGES] | *Bleeding risk on anticoagulation: [http://www.globalrph.com/has-bled-score.htm HAS-BLED]; [http://www.globalrph.com/hemorr2hages-bleeding-risk.htm HEMORR2HAGES] | ||
− | |||
[[Category:Venous thromboembolism regimens]] | [[Category:Venous thromboembolism regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Thrombotic disorders]] | [[Category:Thrombotic disorders]] |
Latest revision as of 01:28, 21 July 2024
Section editor | |
---|---|
Benjamin Tillman, MD Vanderbilt University Nashville, TN, USA |
Are you looking for a regimen, but can't find it here? For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
Note that there is a considerable literature on using these agents in the prevention of thromboembolism associated with atrial fibrillation and mechanical heart valves. As these conditions are out of the purview of HemOnc.org, this page primarily focuses on the prevention and treatment of venous thromboembolism (VTE).
- We have moved How I Treat articles to a dedicated page.
Other pages on HemOnc.org regarding management of deep vein thrombosis (DVT) and pulmonary embolism (PE) include:
- Bleeding with anticoagulation
- Deep veins and superficial veins in the arms and legs
- Hypercoagulable state (thrombophilia) evaluation
- Compression stockings and sleeves for management and prophylaxis against postphlebitic (postthrombotic) syndrome[1]
24 regimens on this page
30 variants on this page
|
Living Interactive Systematic Reviews
Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
ACCP
- 2012: Antithrombotic Therapy for VTE Disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines PubMed
ASCO
- 2023: Key et al. Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Guideline Update PubMed
- 2019: Key et al. Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update. PubMed
- 2015: Lyman et al. ASCO Clinical Practice Guideline on VTE prophylaxis and treatment 2014 update PubMed
- 2013: Lyman et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update PubMed
- 2007: Lyman et al. American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. PubMed
ASH
- 2021: Lyman et al. American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer link to PMC article PubMed
- 2020: Ortel et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism link to PMC article PubMed
- 2019: Anderson et al. American Society of Hematology 2019 guidelines for management of venous thromboembolism: prevention of venous thromboembolism in surgical hospitalized patients link to PMC article PubMed
- 2018: Schünemann et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients link to PMC article PubMed
- 2018: Lim et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: diagnosis of venous thromboembolism link to PMC article PubMed
- 2018: Witt et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy link to PMC article PubMed
- 2018: Monagle et al. American Society of Hematology 2018 Guidelines for management of venous thromboembolism: treatment of pediatric venous thromboembolism link to PMC article PubMed
- 2018: Bates et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy link to PMC article PubMed
- 2018: Cuker et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia link to PMC article PubMed
ESMO
- 2023: Falanga et al. Venous thromboembolism in cancer patients: ESMO Clinical Practice Guideline PubMed
IMWG
Current
- IMWG guidelines for the prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma PubMed
ITAC (International Initiative on Thrombosis and Cancer)
- 2022: Farge et al. 2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19 link to PMC article PubMed
- 2019: Farge et al. 2019 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer PubMed
- 2016: Farge et al. International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer PubMed
- 2013: Farge et al. International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer PubMed
NCCN
- NCCN Guidelines - Cancer-Associated Venous Thromboembolic Disease
- 2015: Streiff et al. Cancer-Associated Venous Thromboembolic Disease, Version 1.2015 PubMed
- 2013: Streiff et al. Venous thromboembolic disease. PubMed
- 2011: Streiff et al. Venous thromboembolic disease. link to PMC article PubMed
- 2008: Wagman et al. Venous thromboembolic disease. NCCN. Clinical practice guidelines in oncology. PubMed
- 2006: Wagman et al. Venous thromboembolic disease. Clinical practice guidelines in oncology. PubMed
VTE primary prophylaxis
Apixaban monotherapy
Regimen variant #1, 10-14 days post-op
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Lassen et al. 2009 (ADVANCE-1)] | Not reported | Phase 3 (E-switch-ic) | Enoxaparin | Inconclusive whether non-inferior asymptomatic and symptomatic DVT, nonfatal PE, and death from any cause during treatment (primary endpoint) | Seems to have lower bleeding rate |
Lassen et al. 2010 (ADVANCE-2) | 2007-06-29 to 2008-11-12 | Phase 3 (E-switch-ic) | Enoxaparin | Superior composite primary endpoint | Might have lower bleeding rate |
Preceding treatment
- Total knee replacement
Anticoagulation
- Apixaban (Eliquis) 2.5 mg PO twice per day, beginning 12 to 24 h after wound closure
10- to 14-day course
Regimen variant #2, 35 days post-op
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Lassen et al. 2010 (ADVANCE-3) | 2007-03 to 2009-05 | Phase 3 (E-switch-ic) | Enoxaparin | Superior composite primary endpoint | Did not meet endpoint of major and clinically relevant nonmajor bleeding |
Preceding treatment
- Total hip replacement
Anticoagulation
- Apixaban (Eliquis) 2.5 mg PO twice per day, beginning 12 to 24 h after wound closure
35-day course
Regimen variant #3, 180 days
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Carrier et al. 2018 (AVERT) | 2014-02 to 2018-04 | Phase 3 (E-esc) | Placebo | Superior VTE rate over 180 days (primary endpoint) | Seems to have higher rate of bleeding |
Anticoagulation
- Apixaban (Eliquis) 2.5 mg PO twice per day, beginning within 24 h of initiation of chemotherapy
6-month course
References
- ADVANCE-1: Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Portman RJ. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med. 2009 Aug 6;361(6):594-604. Erratum in: N Engl J Med. 2009 Oct 29;361(18):1814. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00371683
- ADVANCE-2: Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P; ADVANCE-2 investigators. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet. 2010 Mar 6;375(9717):807-15. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00452530
- ADVANCE-3: Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM; ADVANCE-3 Investigators. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med. 2010 Dec 23;363(26):2487-98. link to original article PubMed NCT00423319
- AVERT: Carrier M, Abou-Nassar K, Mallick R, Tagalakis V, Shivakumar S, Schattner A, Kuruvilla P, Hill D, Spadafora S, Marquis K, Trinkaus M, Tomiak A, Lee AYY, Gross PL, Lazo-Langner A, El-Maraghi R, Goss G, Le Gal G, Stewart D, Ramsay T, Rodger M, Witham D, Wells PS; AVERT Investigators. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med. 2019 Feb 21;380(8):711-719. Epub 2018 Dec 4. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02048865
- PREVAPIX-ALL: O'Brien SH, Rodriguez V, Lew G, Newburger JW, Schultz CL, Orgel E, Derr K, Ranalli MA, Esbenshade AJ, Hochberg J, Kang HJ, Dinikina Y, Mills D, Donovan M, Dyme JL, Favatella NA, Mitchell LG; PREVAPIX-ALL investigators. Apixaban versus no anticoagulation for the prevention of venous thromboembolism in children with newly diagnosed acute lymphoblastic leukaemia or lymphoma (PREVAPIX-ALL): a phase 3, open-label, randomised, controlled trial. Lancet Haematol. 2024 Jan;11(1):e27-e37. Epub 2023 Nov 16. link to original article PubMed NCT02369653
Aspirin monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rodgers et al. 2000 (PEP) | 1992-1998 | Phase 3 (E-esc) | Placebo | Superior VTE rate |
Landolfi et al. 2004 (ECLAP) | Not reported | Phase 3 (E-esc) | Placebo | Seems to have superior rate of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes (primary endpoint) |
Palumbo et al. 2011 (GIMEMA MM-03-05) | 2006-05 to 2009-01 | Phase 3 (E-switch-ic) | 1. Enoxaparin 2. Warfarin; low-dose |
Did not meet primary endpoint of serious thromboembolic events, acute cardiovascular events, or sudden deaths during the first 6 months of treatment |
Larocca et al. 2011 (MPRvsMEL200VTE) | 2007-11 to 2009-06 | Phase 3 (E-de-esc) | Enoxaparin | Did not meet primary endpoint of VTE incidence |
Anderson et al. 2013 (EPCAT) | 2007-2010 | Phase 3 (E-de-esc) | Dalteparin | Non-inferior VTE rate at 90 days (primary endpoint) |
Anderson et al. 2018 (EPCAT II) | 2013-01 to 2016-04 | Phase 3 (E-de-esc) | Rivaroxaban | Non-inferior VTE rate at 90 days (primary endpoint) |
O'Toole et al. 2023 (PREVENT CLOT) | 2017-04 to 2021-08 | Randomized (C) | Enoxaparin | Non-inferior death rate at 90 days |
Note: Palumbo et al. 2011 was a substudy looking at thromboprophylaxis in the thalidomide arm. Larocca et al. 2011 was also a substudy looking at thromboprophylaxis in the lenalidomide arm.
References
- PEP: Rodgers A, MacMahon S, Collins R, Prentice C; Pulmonary Embolism Prevention (PEP) trial Collaborative Group. Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial. Lancet. 2000 Apr 15;355(9212):1295-302. link to original article PubMed
- ECLAP: Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, Barbui T; European Collaboration on Low-Dose Aspirin in Polycythemia Vera Investigators. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004 Jan 8;350(2):114-24. link to original article PubMed
- GIMEMA MM-03-05: Palumbo A, Bringhen S, Rossi D, Cavalli M, Larocca A, Ria R, Offidani M, Patriarca F, Nozzoli C, Guglielmelli T, Benevolo G, Callea V, Baldini L, Morabito F, Grasso M, Leonardi G, Rizzo M, Falcone AP, Gottardi D, Montefusco V, Musto P, Petrucci MT, Ciccone G, Boccadoro M. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial. J Clin Oncol. 2010 Dec 1;28(34):5101-9. Epub 2010 Oct 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01063179
- Post-hoc analysis: Bringhen S, Larocca A, Rossi D, Cavalli M, Genuardi M, Ria R, Gentili S, Patriarca F, Nozzoli C, Levi A, Guglielmelli T, Benevolo G, Callea V, Rizzo V, Cangialosi C, Musto P, De Rosa L, Liberati AM, Grasso M, Falcone AP, Evangelista A, Cavo M, Gaidano G, Boccadoro M, Palumbo A. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood. 2010 Dec 2;116(23):4745-53. Epub 2010 Aug 31. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Subgroup analysis: Palumbo A, Cavo M, Bringhen S, Zamagni E, Romano A, Patriarca F, Rossi D, Gentilini F, Crippa C, Galli M, Nozzoli C, Ria R, Marasca R, Montefusco V, Baldini L, Elice F, Callea V, Pulini S, Carella AM, Zambello R, Benevolo G, Magarotto V, Tacchetti P, Pescosta N, Cellini C, Polloni C, Evangelista A, Caravita T, Morabito F, Offidani M, Tosi P, Boccadoro M. Aspirin, warfarin, or enoxaparin thromboprophylaxis in patients with multiple myeloma treated with thalidomide: a phase III, open-label, randomized trial. J Clin Oncol. 2011 Mar 10;29(8):986-93. Epub 2011 Jan 31. link to original article PubMed
- MPRvsMEL200VTE: Larocca A, Cavallo F, Bringhen S, Di Raimondo F, Falanga A, Evangelista A, Cavalli M, Stanevsky A, Corradini P, Pezzatti S, Patriarca F, Cavo M, Peccatori J, Catalano L, Carella AM, Cafro AM, Siniscalchi A, Crippa C, Petrucci MT, Yehuda DB, Beggiato E, Di Toritto TC, Boccadoro M, Nagler A, Palumbo A. Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide. Blood. 2012 Jan 26;119(4):933-9. Epub 2011 Aug 11. link to original article PubMed NCT00551928
- EPCAT: Anderson DR, Dunbar MJ, Bohm ER, Belzile E, Kahn SR, Zukor D, Fisher W, Gofton W, Gross P, Pelet S, Crowther M, MacDonald S, Kim P, Pleasance S, Davis N, Andreou P, Wells P, Kovacs M, Rodger MA, Ramsay T, Carrier M, Vendittoli PA. Aspirin versus low-molecular-weight heparin for extended venous thromboembolism prophylaxis after total hip arthroplasty: a randomized trial. Ann Intern Med. 2013 Jun 4;158(11):800-6. link to original article PubMed ISRCTN11902170
- EPCAT II: Anderson DR, Dunbar M, Murnaghan J, Kahn SR, Gross P, Forsythe M, Pelet S, Fisher W, Belzile E, Dolan S, Crowther M, Bohm E, MacDonald SJ, Gofton W, Kim P, Zukor D, Pleasance S, Andreou P, Doucette S, Theriault C, Abianui A, Carrier M, Kovacs MJ, Rodger MA, Coyle D, Wells PS, Vendittoli PA. Aspirin or rivaroxaban for VTE prophylaxis after hip or knee arthroplasty. N Engl J Med. 2018 Feb 22;378(8):699-707. link to original article PubMed NCT01720108
- PREVENT CLOT: O'Toole RV, Stein DM, O'Hara NN, Frey KP, Taylor TJ, Scharfstein DO, Carlini AR, Sudini K, Degani Y, Slobogean GP, Haut ER, Obremskey W, Firoozabadi R, Bosse MJ, Goldhaber SZ, Marvel D, Castillo RC. Aspirin or Low-Molecular-Weight Heparin for Thromboprophylaxis after a Fracture. N Engl J Med. 2023 Jan 19;388(3):203-213. link to original article PubMed NCT02984384
Betrixaban monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cohen et al. 2016 (APEX-VTE) | 2012-03 to 2015-11 | Phase 3 (E-switch-ic) | Enoxaparin | Might have lower rates of VTE (primary endpoint) |
Note: this APEX trial should not be confused with the one in multiple myeloma.
Anticoagulation
- Betrixaban (Bevyxxa) 160 mg PO once on day 1, then 80 mg PO once per day
35- to 42-day course
References
- APEX-VTE: Cohen AT, Harrington RA, Goldhaber SZ, Hull RD, Wiens BL, Gold A, Hernandez AF, Gibson CM; APEX Investigators. Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med. 2016 Aug 11;375(6):534-44. Epub 2016 May 27. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01583218
Enoxaparin monotherapy
Regimen variant #1, 30 mg every 12 hours
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Geerts et al. 1996 | 1992-11 to 1994-11 | Phase 3 (E-switch-ic) | UFH | Superior DVT rates | No difference in major bleeding rate |
Lassen et al. 2009 (ADVANCE-1)] | Not reported | Phase 3 (C) | Apixaban | Inconclusive whether non-inferior asymptomatic and symptomatic DVT, nonfatal PE, and death from any cause during treatment | Seems to have higher bleeding rate |
O'Toole et al. 2023 (PREVENT CLOT) | 2017-04 to 2021-08 | Randomized (E-esc) | Aspirin | Non-inferior death rate at 90 days (primary endpoint) |
Preceding treatment
- ADVANCE-1: Total knee replacement
- The study population in Geerts et. al. were trauma patients without intracranial hemorrhage. Prophylaxis was initiated within 36 hours of the injury.
Anticoagulation
- Enoxaparin (Lovenox) 30 mg SC every 12 hours, beginning 12 to 24 h after wound closure (ADVANCE-1), 10- to 14-day course
- The comparison arm in Geerts et al. used heparin 5000 units subcutaneous every 12 hours.
Regimen variant #2, 40 mg daily
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Samama et al. 1999 (MEDENOX) | 1996-12 to 1998-07 | Phase 3 (C) | 1. Placebo 2. Enoxaparin; 20 mg daily |
Superior VTE rates |
Hull et al. 2010 (EXCLAIM) | 2002-02 to 2006-03 | Phase 3 (E-esc) | Placebo | Superior composite VTE rate (primary endpoint) |
Erikkson et al. 2008 (RECORD1) | 2006-02 to 2007-03 | Phase 3 (C) | Rivaroxaban | Inferior composite outcome |
Kakkar et al. 2008 (RECORD2) | 2006-02 to 2007-04 | Phase 3 (C) | Rivaroxaban | Inferior composite outcome |
Lassen et al. 2008 (RECORD3) | 2006-02 to 2006-11 | Phase 3 (C) | Rivaroxaban | Inferior composite outcome |
Palumbo et al. 2011 (GIMEMA MM-03-05) | 2006-05 to 2009-01 | Phase 3 (E-switch-ic) | 1. Aspirin 2. Warfarin; low-dose |
Did not meet primary endpoint of serious thromboembolic events, acute cardiovascular events, or sudden deaths during the first 6 months of treatment |
Turpie et al. 2009 (RECORD4) | 2006-06 to 2007-10 | Phase 3 (C) | Rivaroxaban | Seems to have inferior composite outcome |
Lassen et al. 2010 (ADVANCE-3) | 2007-03 to 2009-05 | Phase 3 (C) | Apixaban | Inferior composite primary endpoint |
Goldhaber et al. 2011 (ADOPT) | 2007-06 to 2011-02 | Phase 3 (C) | Apixaban | Did not meet primary endpoint of 30-day composite of death related to venous thromboembolism, pulmonary embolism, symptomatic deep-vein thrombosis, or asymptomatic proximal-leg deep-vein thrombosis |
Lassen et al. 2010 (ADVANCE-2) | 2007-06-29 to 2008-11-12 | Phase 3 (C) | Apixaban | Inferior composite primary endpoint |
Larocca et al. 2011 (MPRvsMEL200VTE) | 2007-11 to 2009-06 | Phase 3 (E-esc) | Aspirin | Did not meet primary endpoint of VTE incidence |
Cohen et al. 2013 (MAGELLAN) | 2007-12 to 2010-07 | Phase 3 (C) | Rivaroxaban | Non-inferior VTE rate at 10 days |
Kakkar et al. 2011 (LIFENOX) | 2008-01 to 2010-09 | Phase 3 (E-esc) | Placebo | Did not meet primary endpoint of death rate at 30 days |
Cohen et al. 2016 (APEX-VTE) | 2012-03 to 2015-11 | Phase 3 (C) | Betrixaban | Might have higher rates of VTE |
Sidhu et al. 2022 (CRISTAL) | 2019-04-20 to 2020-12-18 | Phase 3 (C) | Aspirin | Superior rate of symptomatic VTE within 90 days |
Note: the APEX trial here should not be confused with the one in multiple myeloma. Larocca et al. 2011 was a substudy looking at thromboprophylaxis in the lenalidomide arm.
Preceding treatment
- ADVANCE-2 & CRISTAL: Total knee replacement
- ADVANCE-3 & CRISTAL: Total hip replacement
Anticoagulation
- Enoxaparin (Lovenox) 40 mg SC once per day
Various durations: 6 to 14 days (APEX-VTE); other (see papers for details)
References
- Geerts WH, Jay RM, Code KI, Chen E, Szalai JP, Saibil EA, Hamilton PA. A comparison of low-dose heparin with low-molecular-weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med. 1996 Sep 5;335(10):701-7. link to original article PubMed
- MEDENOX: Samama MM, Cohen AT, Darmon JY, Desjardins L, Eldor A, Janbon C, Leizorovicz A, Nguyen H, Olsson CG, Turpie AG, Weisslinger N; MEDENOX Investigators. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. N Engl J Med. 1999; 341:793-800. link to original article. PubMed.
- RECORD2: Kakkar AK, Brenner B, Dahl OE, Eriksson BI, Mouret P, Muntz J, Soglian AG, Pap AF, Misselwitz F, Haas S; RECORD2 Investigators. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet. 2008 Jul 5;372(9632):31-9. Epub 2008 Jun 24. link to original article PubMed NCT00332020
- RECORD1: Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, Bandel TJ, Beckmann H, Muehlhofer E, Misselwitz F, Geerts W; RECORD1 Study Group. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008 Jun 26;358(26):2765-75. link to original article PubMed NCT00329628
- RECORD3: Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, Misselwitz F, Turpie AG; RECORD3 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008 Jun 26;358(26):2776-86. link to original article PubMed NCT00361894
- RECORD4: Turpie AG, Lassen MR, Davidson BL, Bauer KA, Gent M, Kwong LM, Cushner FD, Lotke PA, Berkowitz SD, Bandel TJ, Benson A, Misselwitz F, Fisher WD; RECORD4 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. 2009 May 16;373(9676):1673-80. Epub 2009 May 4. link to original article PubMed NCT00362232
- ADVANCE-1: Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Portman RJ. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med. 2009 Aug 6;361(6):594-604. Erratum in: N Engl J Med. 2009 Oct 29;361(18):1814. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00371683
- ADVANCE-2: Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P; ADVANCE-2 investigators. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet. 2010 Mar 6;375(9717):807-15. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00452530
- EXCLAIM: Hull RD, Schellong SM, Tapson VF, Monreal M, Samama MM, Nicol P, Vicaut E, Turpie AG, Yusen RD; EXCLAIM (Extended Prophylaxis for Venous ThromboEmbolism in Acutely Ill Medical Patients With Prolonged Immobilization) study. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial. Ann Intern Med. 2010 Jul 6;153(1):8-18. link to original article PubMed NCT00077753
- ADVANCE-3: Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM; ADVANCE-3 Investigators. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med. 2010 Dec 23;363(26):2487-98. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00423319
- GIMEMA MM-03-05: Palumbo A, Cavo M, Bringhen S, Zamagni E, Romano A, Patriarca F, Rossi D, Gentilini F, Crippa C, Galli M, Nozzoli C, Ria R, Marasca R, Montefusco V, Baldini L, Elice F, Callea V, Pulini S, Carella AM, Zambello R, Benevolo G, Magarotto V, Tacchetti P, Pescosta N, Cellini C, Polloni C, Evangelista A, Caravita T, Morabito F, Offidani M, Tosi P, Boccadoro M. Aspirin, warfarin, or enoxaparin thromboprophylaxis in patients with multiple myeloma treated with thalidomide: a phase III, open-label, randomized trial. J Clin Oncol. 2011 Mar 10;29(8):986-93. Epub 2011 Jan 31. link to original article PubMed NCT01063179
- MPRvsMEL200VTE: Larocca A, Cavallo F, Bringhen S, Di Raimondo F, Falanga A, Evangelista A, Cavalli M, Stanevsky A, Corradini P, Pezzatti S, Patriarca F, Cavo M, Peccatori J, Catalano L, Carella AM, Cafro AM, Siniscalchi A, Crippa C, Petrucci MT, Yehuda DB, Beggiato E, Di Toritto TC, Boccadoro M, Nagler A, Palumbo A. Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide. Blood. 2012 Jan 26;119(4):933-9. Epub 2011 Aug 11. link to original article PubMed NCT00551928
- ADOPT: Goldhaber SZ, Leizorovicz A, Kakkar AK, Haas SK, Merli G, Knabb RM, Weitz JI; ADOPT Trial Investigators. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med. 2011 Dec 8;365(23):2167-77. Epub 2011 Nov 13. link to original article PubMed NCT00457002
- LIFENOX: Kakkar AK, Cimminiello C, Goldhaber SZ, Parakh R, Wang C, Bergmann JF; LIFENOX Investigators. Low-molecular-weight heparin and mortality in acutely ill medical patients. N Engl J Med. 2011 Dec 29;365(26):2463-72. link to original article PubMed NCT00622648
- MAGELLAN: Cohen AT, Spiro TE, Büller HR, Haskell L, Hu D, Hull R, Mebazaa A, Merli G, Schellong S, Spyropoulos AC, Tapson V; MAGELLAN Investigators. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med. 2013 Feb 7;368(6):513-23. link to original article PubMed NCT00571649
- APEX-VTE: Cohen AT, Harrington RA, Goldhaber SZ, Hull RD, Wiens BL, Gold A, Hernandez AF, Gibson CM; APEX Investigators. Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med. 2016 Aug 11;375(6):534-44. Epub 2016 May 27. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01583218
- CRISTAL: Sidhu VS, Kelly TL, Pratt N, Graves SE, Buchbinder R, Adie S, Cashman K, Ackerman I, Bastiras D, Brighton R, Burns AWR, Chong BH, Clavisi O, Cripps M, Dekkers M, de Steiger R, Dixon M, Ellis A, Griffith EC, Hale D, Hansen A, Harris A, Hau R, Horsley M, James D, Khorshid O, Kuo L, Lewis P, Lieu D, Lorimer M, MacDessi S, McCombe P, McDougall C, Mulford J, Naylor JM, Page RS, Radovanovic J, Solomon M, Sorial R, Summersell P, Tran P, Walter WL, Webb S, Wilson C, Wysocki D, Harris IA; CRISTAL Study Group. Effect of Aspirin vs Enoxaparin on Symptomatic Venous Thromboembolism in Patients Undergoing Hip or Knee Arthroplasty: The CRISTAL Randomized Trial. JAMA. 2022 Aug 23;328(8):719-727. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed ACTRN12618001879257
- PREVENT CLOT: O'Toole RV, Stein DM, O'Hara NN, Frey KP, Taylor TJ, Scharfstein DO, Carlini AR, Sudini K, Degani Y, Slobogean GP, Haut ER, Obremskey W, Firoozabadi R, Bosse MJ, Goldhaber SZ, Marvel D, Castillo RC. Aspirin or Low-Molecular-Weight Heparin for Thromboprophylaxis after a Fracture. N Engl J Med. 2023 Jan 19;388(3):203-213. link to original article PubMed NCT02984384
Rivaroxaban monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Erikkson et al. 2008 (RECORD1) | 2006-02 to 2007-03 | Phase 3 (E-switch-ic) | Enoxaparin | Superior composite outcome (primary endpoint) |
Kakkar et al. 2008 (RECORD2) | 2006-02 to 2007-04 | Phase 3 (E-switch-ic) | Enoxaparin | Superior composite outcome (primary endpoint) |
Lassen et al. 2008 (RECORD3) | 2006-02 to 2006-11 | Phase 3 (E-switch-ic) | Enoxaparin | Superior composite outcome (primary endpoint) |
Turpie et al. 2009 (RECORD4) | 2006-06 to 2007-10 | Phase 3 (E-switch-ic) | Enoxaparin | Seems to have superior composite outcome (primary endpoint) |
Cohen et al. 2013 (MAGELLAN) | 2007-12 to 2010-07 | Phase 3 (E-switch-ic) | Enoxaparin | Non-inferior VTE rate at 10 days (co-primary endpoint) |
Anderson et al. 2018 (EPCAT II) | 2013-01 to 2016-04 | Phase 3 (E-esc) | Aspirin | Non-inferior VTE rate at 90 days (primary endpoint) |
Spyropoulos et al. 2018 (MARINER) | 2014-06 to 2018-01 | Phase 3 (E-esc) | Placebo | Did not meet primary endpoint of symptomatic VTE or death due to VTE |
Anticoagulation
- Rivaroxaban (Xarelto) 10 mg PO once per day for varying durations (see individual studies)
References
- RECORD2: Kakkar AK, Brenner B, Dahl OE, Eriksson BI, Mouret P, Muntz J, Soglian AG, Pap AF, Misselwitz F, Haas S; RECORD2 Investigators. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet. 2008 Jul 5;372(9632):31-9. Epub 2008 Jun 24. link to original article PubMed NCT00332020
- RECORD1: Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, Bandel TJ, Beckmann H, Muehlhofer E, Misselwitz F, Geerts W; RECORD1 Study Group. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008 Jun 26;358(26):2765-75. link to original article PubMed NCT00329628
- RECORD3: Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, Misselwitz F, Turpie AG; RECORD3 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008 Jun 26;358(26):2776-86. link to original article PubMed NCT00361894
- RECORD4: Turpie AG, Lassen MR, Davidson BL, Bauer KA, Gent M, Kwong LM, Cushner FD, Lotke PA, Berkowitz SD, Bandel TJ, Benson A, Misselwitz F, Fisher WD; RECORD4 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. 2009 May 16;373(9676):1673-80. Epub 2009 May 4. link to original article PubMed NCT00362232
- MAGELLAN: Cohen AT, Spiro TE, Büller HR, Haskell L, Hu D, Hull R, Mebazaa A, Merli G, Schellong S, Spyropoulos AC, Tapson V; MAGELLAN Investigators. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med. 2013 Feb 7;368(6):513-23. link to original article PubMed NCT00571649
- EPCAT II: Anderson DR, Dunbar M, Murnaghan J, Kahn SR, Gross P, Forsythe M, Pelet S, Fisher W, Belzile E, Dolan S, Crowther M, Bohm E, MacDonald SJ, Gofton W, Kim P, Zukor D, Pleasance S, Andreou P, Doucette S, Theriault C, Abianui A, Carrier M, Kovacs MJ, Rodger MA, Coyle D, Wells PS, Vendittoli PA. Aspirin or rivaroxaban for VTE prophylaxis after hip or knee arthroplasty. N Engl J Med. 2018 Feb 22;378(8):699-707. link to original article PubMed NCT01720108
- MARINER: Spyropoulos AC, Ageno W, Albers GW, Elliott CG, Halperin JL, Hiatt WR, Maynard GA, Steg PG, Weitz JI, Suh E, Spiro TE, Barnathan ES, Raskob GE; MARINER Investigators. Rivaroxaban for thromboprophylaxis after hospitalization for medical illness. N Engl J Med. 2018 Sep 20;379(12):1118-1127. Epub 2018 Aug 26. link to original article PubMed NCT02111564
VTE secondary prevention
Apixaban monotherapy
Regimen variant #1, 2.5 mg twice per day
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Agnelli et al. 2012 (AMPLIFY-EXT) | 2008-05 to 2011-07 | Phase 3 (E-esc) | 1. Apixaban; 5 mg twice per day | Did not meet primary endpoint of symptomatic recurrent VTE or death from any cause |
2. Placebo | Superior symptomatic recurrent VTE or death from any cause |
Preceding treatment
- Therapeutic anticoagulation x 6-12 mo
Regimen variant #2, 5 mg twice per day
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Agnelli et al. 2012 (AMPLIFY-EXT) | 2008-05 to 2011-07 | Phase 3 (E-esc) | 1. Apixaban; 2.5 mg twice per day | Did not meet primary endpoint of symptomatic recurrent VTE or death from any cause |
2. Placebo | Superior symptomatic recurrent VTE or death from any cause |
Preceding treatment
- Therapeutic anticoagulation x 6-12 mo
References
- AMPLIFY-EXT: Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Porcari A, Raskob GE, Weitz JI; AMPLIFY-EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):699-708. Epub 2012 Dec 8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Aspirin monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Brighton et al. 2012 (ASPIRE-VTE) | 2003-05 to 2011-08 | Phase 3 (E-esc) | Placebo | Might have superior rate of VTE recurrence (primary endpoint) | No difference in bleeding rate |
Becattini et al. 2012 (WARFASA) | 2004-05 to 2010-08 | Phase 3 (E-esc) | Placebo | Superior rate of VTE recurrence (primary endpoint) | No difference in bleeding rate |
Note: ASPIRE should not be confused with the multiple myeloma trial of the same name.
References
- WARFASA: Becattini C, Agnelli G, Schenone A, Eichinger S, Bucherini E, Silingardi M, Bianchi M, Moia M, Ageno W, Vandelli MR, Grandone E, Prandoni P; WARFASA Investigators. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med. 2012 May 24;366(21):1959-67. Erratum in: N Engl J Med. 2012 Oct 18;367(16):1573. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00222677
- ASPIRE-VTE: Brighton TA, Eikelboom JW, Mann K, Mister R, Gallus A, Ockelford P, Gibbs H, Hague W, Xavier D, Diaz R, Kirby A, Simes J; ASPIRE Investigators. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med. 2012 Nov 22;367(21):1979-87. Epub 2012 Nov 4. link to original article PubMed ACTRN12605000004662
Dalteparin monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Lee et al. 2003 (CLOT) | 1999-05 to 2001-10 | Phase 3 (E-switch-ic) | Warfarin | Superior rate of VTE at 6 months (primary endpoint) | No difference in bleeding rate |
Anticoagulation
- Dalteparin (Fragmin) as follows:
- Month 1: 200 IU/kg SC once per day
- Months 2 to 6: 150 IU/kg SC once per day
6-month course
References
- CLOT: Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M; Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003 Jul 10;349(2):146-53. link to original article PubMed
- Post-hoc analysis: Lee AY, Rickles FR, Julian JA, Gent M, Baker RI, Bowden C, Kakkar AK, Prins M, Levine MN. Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism. J Clin Oncol. 2005 Apr 1;23(10):2123-9. Epub 2005 Feb 7. link to original article PubMed
Enoxaparin monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Meyer et al. 2002 | 1995-04 to 1999-03 | Phase 3 (E-switch-ic) | Warfarin | Might have superior composite VTE/bleeding outcome (primary endpoint) |
References
- Decousus H, Leizorovicz A, Parent F, Page Y, Tardy B, Girard P, Laporte S, Faivre R, Charbonnier B, Barral FG, Huet Y, Simonneau G; Prévention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group. A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. N Engl J Med. 1998 Feb 12;338(7):409-15. link to original article PubMed
- Meyer G, Marjanovic Z, Valcke J, Lorcerie B, Gruel Y, Solal-Celigny P, Le Maignan C, Extra JM, Cottu P, Farge D. Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. Arch Intern Med. 2002 Aug 12-26;162(15):1729-35. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Highlow: Bistervels IM, Buchmüller A, Wiegers HMG, Ní Áinle F, Tardy B, Donnelly J, Verhamme P, Jacobsen AF, Hansen AT, Rodger MA, DeSancho MT, Shmakov RG, van Es N, Prins MH, Chauleur C, Middeldorp S; Highlow Block writing committee; Highlow Investigators. Intermediate-dose versus low-dose low-molecular-weight heparin in pregnant and post-partum women with a history of venous thromboembolism (Highlow study): an open-label, multicentre, randomised, controlled trial. Lancet. 2022 Oct 28:S0140-6736(22)02128-6. link to original article PubMed NCT01828697
Warfarin monotherapy
Regimen variant #1, standard intensity
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Meyer et al. 2002 | 1995-04-02 to 1999-03-31 | Phase 3 (C) | Enoxaparin | Might have inferior composite VTE/bleeding outcome | |
Lee et al. 2003 (CLOT) | 1999-05 to 2001-10 | Phase 3 (C) | Dalteparin | Inferior rate of VTE at 6 months | No difference in bleeding rate |
Anticoagulation
- Warfarin (Coumadin) PO titrated to goal INR 2 to 3.0
Regimen variant #2, low intensity
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Ridker et al. 2003 (PREVENT) | 1998-07-06 to 2002-12-04 | Phase 3 (E-esc) | Placebo | Superior recurrent VTE rate (primary endpoint) | No difference in major bleeding |
Preceding treatment
- Warfarin with goal INR of 2 to 3 for median of 6.5 mo
References
- Meyer G, Marjanovic Z, Valcke J, Lorcerie B, Gruel Y, Solal-Celigny P, Le Maignan C, Extra JM, Cottu P, Farge D. Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. Arch Intern Med. 2002 Aug 12-26;162(15):1729-35. link to original article PubMed
- Kearon C, Ginsberg JS, Kovacs MJ, Anderson DR, Wells P, Julian JA, MacKinnon B, Weitz JI, Crowther MA, Dolan S, Turpie AG, Geerts W, Solymoss S, van Nguyen P, Demers C, Kahn SR, Kassis J, Rodger M, Hambleton J, Gent M; Extended Low-Intensity Anticoagulation for Thrombo-Embolism Investigators. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med. 2003 Aug 14;349(7):631-9. link to original article PubMed
- PREVENT: Ridker PM, Goldhaber SZ, Danielson E, Rosenberg Y, Eby CS, Deitcher SR, Cushman M, Moll S, Kessler CM, Elliott CG, Paulson R, Wong T, Bauer KA, Schwartz BA, Miletich JP, Bounameaux H, Glynn RJ; PREVENT Investigators. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med. 2003 Apr 10;348(15):1425-34. Epub 2003 Feb 24. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- CLOT: Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M; Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003 Jul 10;349(2):146-53. link to original article PubMed
- Post-hoc analysis: Lee AY, Rickles FR, Julian JA, Gent M, Baker RI, Bowden C, Kakkar AK, Prins M, Levine MN. Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism. J Clin Oncol. 2005 Apr 1;23(10):2123-9. Epub 2005 Feb 7. link to original article PubMed
VTE treatment, all lines of therapy
Apixaban monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Agnelli et al. 2013 (AMPLIFY) | 2008-08 to 2012-08 | Phase 3 (E-switch-ooc) | Warfarin | Non-inferior composite primary endpoint | Lower rates of bleeding |
McBane et al. 2019 (ADAM VTE) | 2015-11-20 to 2017-10-02 | Phase 3 (E-switch-ooc) | Dalteparin | Might have lower rates of major bleeding (primary endpoint) | |
Angelli et al. 2020 (CARAVAGGIO) | 2017-04 to 2019-06 | Phase 3 (E-switch-ooc) | Dalteparin | Non-inferior recurrent VTE (primary endpoint) | Major bleeding similar in both groups |
Anticoagulation
- Apixaban (Eliquis) 10 mg PO twice per day for 7 days, then 5 mg PO twice per day
6-month course
References
- AMPLIFY: Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013 Aug 29;369(9):799-808. Epub 2013 Jul 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00643201
- ADAM VTE: McBane RD 2nd, Wysokinski WE, Le-Rademacher JG, Zemla T, Ashrani A, Tafur A, Perepu U, Anderson D, Gundabolu K, Kuzma C, Perez Botero J, Leon Ferre RA, Henkin S, Lenz CJ, Houghton DE, Vishnu P, Loprinzi CL. Apixaban and dalteparin in active malignancy-associated venous thromboembolism: The ADAM VTE trial. J Thromb Haemost. 2020 Feb;18(2):411-421. Epub 2019 Nov 28. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT02585713
- CARAVAGGIO: Agnelli G, Becattini C, Meyer G, Munoz A, Huisman M, Connors J, Cohen A, Bauersachs R, Brenner B, Torbicki A, Sueiro M, Lambert C, Gussoni G, Campanini M, Fontanella A, Vescovo G, Verso M, Caravaggio Investigators. Apixaban for the treatment of venous thromboembolism associated with cancer. N Engl J Med. 2020 Apr 23;382(17):1599-1607. Epub 2020 Mar 29. link to original article PubMed NCT03045406
Argatroban monotherapy
Regimen
Anticoagulation
References
To be completed
Aspirin monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Weitz et al. 2017 (EINSTEIN CHOICE) | 2014-03 to 2016-03 | Phase 3 (C) | 1. Rivaroxaban; 10 mg/day 2. Rivaroxaban; 20 mg/day |
Inferior symptomatic recurrent VTE rate | Similar major bleeding |
Preceding treatment
- 6 to 12 months of a vitamin K antagonist or a direct oral anticoagulant
References
- EINSTEIN CHOICE: Weitz JI, Lensing AWA, Prins MH, Bauersachs R, Beyer-Westendorf J, Bounameaux H, Brighton TA, Cohen AT, Davidson BL, Decousus H, Freitas MCS, Holberg G, Kakkar AK, Haskell L, van Bellen B, Pap AF, Berkowitz SD, Verhamme P, Wells PS, Prandoni P; EINSTEIN CHOICE Investigators. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med. 2017 Mar 30;376(13):1211-1222. Epub 2017 Mar 18. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02064439
Bivalirudin monotherapy
Regimen
Anticoagulation
References
To be completed
Dabigatran monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Schulman et al. 2009 (RE-COVER) | 2006-04 to 2008-11 | Phase 3 (E-switch-ic) | Warfarin | Non-inferior composite primary endpoint | Similar major bleeding |
References
- RE-COVER: Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H, Baanstra D, Schnee J, Goldhaber SZ; RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009 Dec 10;361(24):2342-52. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00291330
- RE-MEDY: Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, Kvamme AM, Friedman J, Mismetti P, Goldhaber SZ; RE-MEDY Trial Investigators; RE-SONATE Trial Investigators. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):709-18. link to original article PubMed NCT00329238
- RE-COVER II: Schulman S, Kakkar AK, Goldhaber SZ, Schellong S, Eriksson H, Mismetti P, Christiansen AV, Friedman J, Le Maulf F, Peter N, Kearon C; RE-COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014 Feb 18;129(7):764-72. Epub 2013 Dec 16. link to original article PubMed NCT00680186
- DIVERSITY: Halton J, Brandão LR, Luciani M, Bomgaars L, Chalmers E, Mitchell LG, Nurmeev I, Sharathkumar A, Svirin P, Gorbatikov K, Tartakovsky I, Simetzberger M, Huang F, Sun Z, Kreuzer J, Gropper S, Reilly P, Brueckmann M, Albisetti M; DIVERSITY Trial Investigators. Dabigatran etexilate for the treatment of acute venous thromboembolism in children (DIVERSITY): a randomised, controlled, open-label, phase 2b/3, non-inferiority trial. Lancet Haematol. 2021 Jan;8(1):e22-e33. Epub 2020 Dec 5. link to original article PubMed NCT01895777
Dalteparin monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Francis et al. 2015 (DALTECAN) | 2009-06 to 2011-03 | Non-randomized | |||
Young et al. 2018 (SELECT-D) | 2013-09-06 to 2016-12-22 | Phase 3 (C) | Rivaroxaban | Seems to have inferior rate of VTE recurrence | Superior rates of clinically relevant non-major bleeding |
Raskob et al. 2017 (Hokusai VTE Cancer) | 2015-07 to 2016-12 | Phase 3 (C) | Edoxaban | Non-inferior composite endpoint of VTE/major bleeding | Non-inferior composite endpoint of VTE/major bleeding |
Angelli et al. 2020 (CARAVAGGIO) | 2017-04 to 2019-06 | Phase 3 (C) | Apixaban | Non-inferior recurrent VTE | Major bleeding similar in both groups |
Anticoagulation
- Dalteparin (Fragmin) as follows:
- Month 1: 200 IU/kg once per day
- Months 2 to 6 up to 12: 150 IU/kg once per day
6- to 12-month course
References
- DALTECAN: Francis CW, Kessler CM, Goldhaber SZ, Kovacs MJ, Monreal M, Huisman MV, Bergqvist D, Turpie AG, Ortel TL, Spyropoulos AC, Pabinger I, Kakkar AK. Treatment of venous thromboembolism in cancer patients with dalteparin for up to 12 months: the DALTECAN Study. J Thromb Haemost. 2015 Jun;13(6):1028-35. Epub 2015 May 10. link to original article PubMed NCT00942968
- Hokusai VTE Cancer: Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia D, Grosso MA, Kakkar AK, Kovacs MJ, Mercuri MF, Meyer G, Segers A, Shi M, Wang TF, Yeo E, Zhang G, Zwicker JI, Weitz JI, Büller HR; Hokusai VTE Cancer Investigators. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med. 2018 Feb 15;378(7):615-624. Epub 2017 Dec 12. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT02073682
- SELECT-D: Young AM, Marshall A, Thirlwall J, Chapman O, Lokare A, Hill C, Hale D, Dunn JA, Lyman GH, Hutchinson C, MacCallum P, Kakkar A, Hobbs FDR, Petrou S, Dale J, Poole CJ, Maraveyas A, Levine M. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol. 2018 Jul 10;36(20):2017-2023. Epub 2018 May 10. link to original article dosing details in abstract have been reviewed by our editors PubMed ISRCTN86712308
- ADAM VTE: McBane RD 2nd, Wysokinski WE, Le-Rademacher JG, Zemla T, Ashrani A, Tafur A, Perepu U, Anderson D, Gundabolu K, Kuzma C, Perez Botero J, Leon Ferre RA, Henkin S, Lenz CJ, Houghton DE, Vishnu P, Loprinzi CL. Apixaban and dalteparin in active malignancy-associated venous thromboembolism: The ADAM VTE trial. J Thromb Haemost. 2020 Feb;18(2):411-421. Epub 2019 Nov 28. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT02585713
- CARAVAGGIO: Agnelli G, Becattini C, Meyer G, Munoz A, Huisman M, Connors J, Cohen A, Bauersachs R, Brenner B, Torbicki A, Sueiro M, Lambert C, Gussoni G, Campanini M, Fontanella A, Vescovo G, Verso M, Caravaggio Investigators. Apixaban for the treatment of venous thromboembolism associated with cancer. N Engl J Med. 2020 Apr 23;382(17):1599-1607. Epub 2020 Mar 29. link to original article PubMed NCT03045406
Edoxaban monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Büller et al. 2013 (Hokusai-VTE) | 2010-01 to 2012-10 | Phase 3 (E-RT-switch-ic) | Warfarin | Non-inferior recurrent symptomatic VTE rate (primary endpoint) Symptomatic VTE rate: 3.2% vs 3.5% (HR 0.89, 95% CI 0.70-1.13) |
Lower rates of bleeding |
Raskob et al. 2017 (Hokusai VTE Cancer) | 2015-07 to 2016-12 | Phase 3 (E-RT-switch-ic) | Dalteparin | Non-inferior composite primary endpoint of VTE/major bleeding | Non-inferior composite primary endpoint of VTE/major bleeding |
Anticoagulation
- Therapeutic dose LMWH for at least 5 days, then:
- Edoxaban (Savaysa) 60 mg PO once per day
3- to 12-month course
Dose and schedule modifications
- Edoxaban (Savaysa): Patients with CrCl 30 to 50 mL/min/1.73 m2, a body weight of up to 60 kg, or those taking "potent" P-glycoprotein inhibitors: 30 mg PO once per day
References
- Hokusai-VTE: Büller HR, Décousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, Shi M, Verhamme P, Wells P; Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013 Oct 10;369(15):1406-15. Epub 2013 Aug 31. Erratum in: N Engl J Med. 2014 Jan 23;370(4):390. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00986154
- Subgroup analysis: Raskob GE, van Es N, Segers A, Angchaisuksiri P, Oh D, Boda Z, Lyons RM, Meijer K, Gudz I, Weitz JI, Zhang G, Lanz H, Mercuri MF, Büller HR; Hokusai-VTE investigators. Edoxaban for venous thromboembolism in patients with cancer: results from a non-inferiority subgroup analysis of the Hokusai-VTE randomised, double-blind, double-dummy trial. Lancet Haematol. 2016 Aug;3(8):e379-87. Epub 2016 Jul 1. link to original article PubMed
- Hokusai VTE Cancer: Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia D, Grosso MA, Kakkar AK, Kovacs MJ, Mercuri MF, Meyer G, Segers A, Shi M, Wang TF, Yeo E, Zhang G, Zwicker JI, Weitz JI, Büller HR; Hokusai VTE Cancer Investigators. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med. 2018 Feb 15;378(7):615-624. Epub 2017 Dec 12. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT02073682
Enoxaparin monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kearon et al. 2006 (FIDO) | 1998-09 to 2004-02 | Phase 3 (E-switch-ic) | 1. Dalteparin 2. UFH |
No difference in recurrent VTE or major bleeding |
Anticoagulation
- Enoxaparin (Lovenox) 100 IU/kg SC once every 12 hours
References
- FIDO: Kearon C, Ginsberg JS, Julian JA, Douketis J, Solymoss S, Ockelford P, Jackson S, Turpie AG, MacKinnon B, Hirsh J, Gent M; Fixed-Dose Heparin (FIDO) Investigators. Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism. JAMA. 2006 Aug 23;296(8):935-42. link to original article PubMed NCT00182403
Fondaparinux monotherapy
Regimen
Anticoagulation
References
To be completed
Heparin monotherapy
UFH: UnFractionated Heparin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Loewe & Hirsch 1947 | Not reported | Observational | None | 2.4% fatality rate due to pulmonary embolism |
Kearon et al. 2006 (FIDO) | 1998-09 to 2004-02 | Phase 3 (C) | 1. Dalteparin 2. Enoxaparin |
No difference in recurrent VTE or major bleeding |
Note: In Loewe and Hirsch, heparin was administered as a deep subcutaneous injection (200 to 400 mg / 200,000 to 400,000 IU) in Pitkin menstruum every two to three days for 10 to 14 days for deep vein thrombosis and extended for one to two additional weeks for pulmonary embolism.
Anticoagulation
- Unfractionated heparin (UFH) 333 units/kg SC once, then 250 units/kg SC every 12 hours
References
- Loewe L, Hirsch E. Heparin in the treatment of thromboembolic disease. JAMA. 1947;133(17):1263-1268. link to original article PubMed
- FIDO: Kearon C, Ginsberg JS, Julian JA, Douketis J, Solymoss S, Ockelford P, Jackson S, Turpie AG, MacKinnon B, Hirsh J, Gent M; Fixed-Dose Heparin (FIDO) Investigators. Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism. JAMA. 2006 Aug 23;296(8):935-42. link to original article PubMed NCT00182403
Lepirudin monotherapy
Regimen
Anticoagulation
References
To be completed
Rivaroxaban monotherapy
Regimen variant #1, 10 mg/day
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Weitz et al. 2017 (EINSTEIN CHOICE) | 2014-03 to 2016-03 | Phase 3 (E-esc) | 1. Aspirin | Superior symptomatic recurrent VTE rate (primary endpoint) | Similar major bleeding |
2. Rivaroxaban; 20 mg/day | Did not meet primary endpoint of symptomatic recurrent VTE rate | Similar major bleeding |
Preceding treatment
- 6 to 12 months of a vitamin K antagonist or a direct oral anticoagulant
Regimen variant #2, 20 mg/day
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Weitz et al. 2017 (EINSTEIN CHOICE) | 2014-03 to 2016-03 | Phase 3 (E-esc) | 1. Aspirin | Superior symptomatic recurrent VTE rate (primary endpoint) | Similar major bleeding |
2. Rivaroxaban; 10 mg/day | Did not meet primary endpoint of symptomatic recurrent VTE rate | Similar major bleeding |
Preceding treatment
- 6 to 12 months of a vitamin K antagonist or a direct oral anticoagulant
Regimen variant #3, 20 mg/day with loading dose
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Bauersachs et al. 2010 (EINSTEIN Acute DVT) | 2007-03 to 2009-09 | Phase 3 (E-switch-ic) | Warfarin | Non-inferior VTE recurrence (primary endpoint) | Similar major bleeding |
Büller et al. 2012 (EINSTEIN-PE) | 2007-03 to 2011-03 | Phase 3 (E-switch-ic) | Warfarin | Non-inferior symptomatic VTE recurrence (primary endpoint) | Similar major bleeding |
Young et al. 2018 (SELECT-D) | 2013-09-06 to 2016-12-22 | Phase 3 (E-switch-ic) | Dalteparin | Seems to have superior rate of VTE recurrence over 6 months (primary endpoint) | Inferior rates of clinically relevant non-major bleeding |
Anticoagulation
- Rivaroxaban (Xarelto) 15 mg PO twice per day for 3 weeks, then 20 mg PO once per day
3-, 6-, or 12-month course
References
- EINSTEIN Acute DVT: Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, Gallus AS, Lensing AW, Misselwitz F, Prins MH, Raskob GE, Segers A, Verhamme P, Wells P, Agnelli G, Bounameaux H, Cohen A, Davidson BL, Piovella F, Schellong S; EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010 Dec 23;363(26):2499-510. Epub 2010 Dec 3. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00440193; NCT00439725
- EINSTEIN-PE: Büller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A; EINSTEIN-PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012 Apr 5;366(14):1287-97. Epub 2012 Mar 26. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00439777
- XALIA: Ageno W, Mantovani LG, Haas S, Kreutz R, Monje D, Schneider J, van Eickels M, Gebel M, Zell E, Turpie AG. Safety and effectiveness of oral rivaroxaban versus standard anticoagulation for the treatment of symptomatic deep-vein thrombosis (XALIA): an international, prospective, non-interventional study. Lancet Haematol. 2016 Jan;3(1):e12-21. Epub 2015 Dec 8. link to original article PubMed NCT01619007
- EINSTEIN CHOICE: Weitz JI, Lensing AWA, Prins MH, Bauersachs R, Beyer-Westendorf J, Bounameaux H, Brighton TA, Cohen AT, Davidson BL, Decousus H, Freitas MCS, Holberg G, Kakkar AK, Haskell L, van Bellen B, Pap AF, Berkowitz SD, Verhamme P, Wells PS, Prandoni P; EINSTEIN CHOICE Investigators. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med. 2017 Mar 30;376(13):1211-1222. Epub 2017 Mar 18. link to original article PubMed NCT02064439
- SELECT-D: Young AM, Marshall A, Thirlwall J, Chapman O, Lokare A, Hill C, Hale D, Dunn JA, Lyman GH, Hutchinson C, MacCallum P, Kakkar A, Hobbs FDR, Petrou S, Dale J, Poole CJ, Maraveyas A, Levine M. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol. 2018 Jul 10;36(20):2017-2023. Epub 2018 May 10. link to original article dosing details in abstract have been reviewed by our editors PubMed ISRCTN86712308
- EINSTEIN Junior: Male C, Lensing AWA, Palumbo JS, Kumar R, Nurmeev I, Hege K, Bonnet D, Connor P, Hooimeijer HL, Torres M, Chan AKC, Kenet G, Holzhauer S, Santamaría A, Amedro P, Chalmers E, Simioni P, Bhat RV, Yee DL, Lvova O, Beyer-Westendorf J, Biss TT, Martinelli I, Saracco P, Peters M, Kállay K, Gauger CA, Massicotte MP, Young G, Pap AF, Majumder M, Smith WT, Heubach JF, Berkowitz SD, Thelen K, Kubitza D, Crowther M, Prins MH, Monagle P; EINSTEIN-Jr Phase 3 Investigators. Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial. Lancet Haematol. 2020 Jan;7(1):e18-e27. Epub 2019 Nov 5. link to original article PubMed NCT02234843
Tinzaparin monotherapy
Regimen
Note: this agent has been withdrawn from the US market.
Anticoagulation
References
- LITE: Hull RD, Pineo GF, Brant RF, Mah AF, Burke N, Dear R, Wong T, Cook R, Solymoss S, Poon MC, Raskob G; LITE Trial Investigators. Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer. Am J Med. 2006 Dec;119(12):1062-72. link to original article PubMed
- CATCH: Lee AY, Kamphuisen PW, Meyer G, Bauersachs R, Janas MS, Jarner MF, Khorana AA; CATCH Investigators. Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: A randomized clinical trial. JAMA. 2015 Aug 18;314(7):677-86. link to original article PubMed NCT01130025
Warfarin monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Schulman et al. 2009 (RE-COVER) | 2006-04 to 2008-11 | Phase 3 (C) | Dabigatran | Non-inferior composite endpoint | Similar major bleeding |
Bauersachs et al. 2010 (EINSTEIN Acute DVT) | 2007-03 to 2009-09 | Phase 3 (C) | Rivaroxaban | Non-inferior VTE recurrence | Similar major bleeding |
Büller et al. 2012 (EINSTEIN-PE) | 2007-03 to 2011-03 | Phase 3 (C) | Rivaroxaban | Non-inferior symptomatic VTE recurrence (primary endpoint) | Similar major bleeding |
Agnelli et al. 2013 (AMPLIFY) | 2008-08 to 2012-08 | Phase 3 (C) | Apixaban | Non-inferior composite primary endpoint | Higher rates of bleeding |
Büller et al. 2013 (Hokusai-VTE) | 2010-01 to 2012-10 | Phase 3 (C) | Edoxaban | Non-inferior recurrent VTE rate | Higher rates of bleeding |
Lee et al. 2015 (CATCH) | 2010-08 to 2013-11 | Phase 3 (C) | Tinzaparin | Might have inferior composite outcome | Similar major bleeding |
Anticoagulation
- Warfarin (Coumadin) with goal INR between 2 and 3.0
Supportive therapy
- Most protocols: Enoxaparin (Lovenox) 1 mg/kg SC once every 12 hours, given until INR greater than 2.0
3-, 6-, or 12- month course (see individual papers)
References
- Schulman S, Rhedin AS, Lindmarker P, Carlsson A, Lärfars G, Nicol P, Loogna E, Svensson E, Ljungberg B, Walter H; Duration of Anticoagulation Trial Study Group. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. N Engl J Med. 1995 Jun 22;332(25):1661-5. link to original article PubMed
- Schulman S, Granqvist S, Holmström M, Carlsson A, Lindmarker P, Nicol P, Eklund SG, Nordlander S, Lärfars G, Leijd B, Linder O, Loogna E; The Duration of Anticoagulation Trial Study Group. The duration of oral anticoagulant therapy after a second episode of venous thromboembolism. N Engl J Med. 1997 Feb 6;336(6):393-8. link to original article PubMed
- Kearon C, Gent M, Hirsh J, Weitz J, Kovacs MJ, Anderson DR, Turpie AG, Green D, Ginsberg JS, Wells P, MacKinnon B, Julian JA. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med. 1999 Mar 25;340(12):901-7. Erratum in: N Engl J Med 1999 Jul 22;341(4):298. link to original article PubMed
- Agnelli G, Prandoni P, Santamaria MG, Bagatella P, Iorio A, Bazzan M, Moia M, Guazzaloca G, Bertoldi A, Tomasi C, Scannapieco G, Ageno W; Warfarin Optimal Duration Italian Trial Investigators. Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis. Warfarin Optimal Duration Italian Trial Investigators. N Engl J Med. 2001 Jul 19;345(3):165-9. link to original article PubMed
- DOTAVK: Pinede L, Ninet J, Duhaut P, Chabaud S, Demolombe-Rague S, Durieu I, Nony P, Sanson C, Boissel JP; Investigators of the "Durée Optimale du Traitement AntiVitamines K" (DOTAVK) Study. Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep vein thrombosis or pulmonary embolism and comparison of 6 and 12 weeks of therapy after isolated calf deep vein thrombosis. Circulation. 2001 May 22;103(20):2453-60. link to original article PubMed
- Agnelli G, Prandoni P, Becattini C, Silingardi M, Taliani MR, Miccio M, Imberti D, Poggio R, Ageno W, Pogliani E, Porro F, Zonzin P; Warfarin Optimal Duration Italian Trial Investigators. Extended oral anticoagulant therapy after a first episode of pulmonary embolism. Ann Intern Med. 2003 Jul 1;139(1):19-25. link to original article PubMed
- SOFAST: Kearon C, Ginsberg JS, Anderson DR, Kovacs MJ, Wells P, Julian JA, Mackinnon B, Demers C, Douketis J, Turpie AG, Van Nguyen P, Green D, Kassis J, Kahn SR, Solymoss S, Desjardins L, Geerts W, Johnston M, Weitz JI, Hirsh J, Gent M; SOFAST Investigators. Comparison of 1 month with 3 months of anticoagulation for a first episode of venous thromboembolism associated with a transient risk factor. J Thromb Haemost. 2004 May;2(5):743-9. link to original article PubMed
- LITE: Hull RD, Pineo GF, Brant RF, Mah AF, Burke N, Dear R, Wong T, Cook R, Solymoss S, Poon MC, Raskob G; LITE Trial Investigators. Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer. Am J Med. 2006 Dec;119(12):1062-72. link to original article PubMed
- RE-COVER: Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H, Baanstra D, Schnee J, Goldhaber SZ; RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009 Dec 10;361(24):2342-52. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00291330
- EINSTEIN Acute DVT: Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, Gallus AS, Lensing AW, Misselwitz F, Prins MH, Raskob GE, Segers A, Verhamme P, Wells P, Agnelli G, Bounameaux H, Cohen A, Davidson BL, Piovella F, Schellong S; EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010 Dec 23;363(26):2499-510. Epub 2010 Dec 3. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00440193; NCT00439725
- EINSTEIN-PE: Büller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A; EINSTEIN-PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012 Apr 5;366(14):1287-97. Epub 2012 Mar 26. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00439777
- RE-MEDY: Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, Kvamme AM, Friedman J, Mismetti P, Goldhaber SZ; RE-MEDY Trial Investigators; RE-SONATE Trial Investigators. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):709-18. link to original article PubMed NCT00329238
- AMPLIFY: Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013 Aug 29;369(9):799-808. Epub 2013 Jul 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00643201
- Hokusai-VTE: Büller HR, Décousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, Shi M, Verhamme P, Wells P; Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013 Oct 10;369(15):1406-15. Epub 2013 Aug 31. Erratum in: N Engl J Med. 2014 Jan 23;370(4):390. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00986154
- Subgroup analysis: Raskob GE, van Es N, Segers A, Angchaisuksiri P, Oh D, Boda Z, Lyons RM, Meijer K, Gudz I, Weitz JI, Zhang G, Lanz H, Mercuri MF, Büller HR; Hokusai-VTE investigators. Edoxaban for venous thromboembolism in patients with cancer: results from a non-inferiority subgroup analysis of the Hokusai-VTE randomised, double-blind, double-dummy trial. Lancet Haematol. 2016 Aug;3(8):e379-87. Epub 2016 Jul 1. link to original article PubMed
- RE-COVER II: Schulman S, Kakkar AK, Goldhaber SZ, Schellong S, Eriksson H, Mismetti P, Christiansen AV, Friedman J, Le Maulf F, Peter N, Kearon C; RE-COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014 Feb 18;129(7):764-72. Epub 2013 Dec 16. link to original article PubMed NCT00680186
- CATCH: Lee AY, Kamphuisen PW, Meyer G, Bauersachs R, Janas MS, Jarner MF, Khorana AA; CATCH Investigators. Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: A randomized clinical trial. JAMA. 2015 Aug 18;314(7):677-86. link to original article PubMed NCT01130025
Additional information
- ACCP Chest guidelines for antithrombotic therapy for venous thromboembolic disease (2016)
- ACCP Chest Guidelines (2012) - Antithrombotic Therapy and Prevention of Thrombosis, 9th edition (2012)
- Bleeding risk on anticoagulation: HAS-BLED; HEMORR2HAGES