Difference between revisions of "Venous thromboembolism"
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''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).'' | ''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).'' | ||
<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]] | ||
*[[Deep veins and superficial veins in the arms and legs]] | *[[Deep veins and superficial veins in the arms and legs]] | ||
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=Guidelines= | =Guidelines= | ||
==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://www.asco.org/ ASCO]== | ==[https://www.asco.org/ ASCO]== | ||
− | *'''2015:''' Lyman et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881372/ ASCO Clinical Practice Guideline on VTE prophylaxis and treatment 2014 update] | + | |
+ | * '''2019:''' Key et al. [https://www.ncbi.nlm.nih.gov/pubmed/31381464 Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update. PubMed] | ||
+ | |||
+ | === Older === | ||
+ | |||
+ | *'''2015:''' Lyman et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881372/ ASCO Clinical Practice Guideline on VTE prophylaxis and treatment 2014 update] | ||
*'''2013:''' Lyman et al. [https://ascopubs.org/doi/abs/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://www.ncbi.nlm.nih.gov/pubmed/23669224 PubMed] | *'''2013:''' Lyman et al. [https://ascopubs.org/doi/abs/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://www.ncbi.nlm.nih.gov/pubmed/23669224 PubMed] | ||
− | |||
*'''2013:''' Lyman et al. [http://jco.ascopubs.org/content/31/17/2189.long ASCO Clinical Practice Guideline on VTE prophylaxis and treatment 2013 update] [https://www.ncbi.nlm.nih.gov/pubmed/23669224 PubMed] | *'''2013:''' Lyman et al. [http://jco.ascopubs.org/content/31/17/2189.long ASCO Clinical Practice Guideline on VTE prophylaxis and treatment 2013 update] [https://www.ncbi.nlm.nih.gov/pubmed/23669224 PubMed] | ||
==[https://www.hematology.org/ ASH]== | ==[https://www.hematology.org/ ASH]== | ||
+ | |||
*'''2018:''' Schünemann et al. [http://www.bloodadvances.org/content/2/22/3198 American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients] | *'''2018:''' Schünemann et al. [http://www.bloodadvances.org/content/2/22/3198 American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients] | ||
*'''2018:''' Lim et al. [http://www.bloodadvances.org/content/2/22/3226 American Society of Hematology 2018 guidelines for management of venous thromboembolism: diagnosis of venous thromboembolism] | *'''2018:''' Lim et al. [http://www.bloodadvances.org/content/2/22/3226 American Society of Hematology 2018 guidelines for management of venous thromboembolism: diagnosis of venous thromboembolism] | ||
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==[http://www.esmo.org/ ESMO]== | ==[http://www.esmo.org/ ESMO]== | ||
+ | |||
*'''2010:''' [http://www.thrombosisresearch.com/article/S0049-3848(10)70028-1/pdf Venous thromboembolism (VTE) in cancer patients. ESMO clinical recommendations for prevention and management] [https://www.ncbi.nlm.nih.gov/pubmed/20433989 PubMed] | *'''2010:''' [http://www.thrombosisresearch.com/article/S0049-3848(10)70028-1/pdf Venous thromboembolism (VTE) in cancer patients. ESMO clinical recommendations for prevention and management] [https://www.ncbi.nlm.nih.gov/pubmed/20433989 PubMed] | ||
==IMWG== | ==IMWG== | ||
===Current=== | ===Current=== | ||
+ | |||
*'''2010:''' [http://imwg.myeloma.org/imwg-guidelines-for-the-prevention-of-thalidomide-and-lenalidomide-associated-thrombosis-in-myeloma/ IMWG guidelines for the prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma] | *'''2010:''' [http://imwg.myeloma.org/imwg-guidelines-for-the-prevention-of-thalidomide-and-lenalidomide-associated-thrombosis-in-myeloma/ IMWG guidelines for the prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma] | ||
===Older=== | ===Older=== | ||
+ | |||
*'''2007:''' [https://www.nature.com/leu/journal/v22/n2/full/2405062a.html Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma] [https://www.ncbi.nlm.nih.gov/pubmed/18094721 PubMed] | *'''2007:''' [https://www.nature.com/leu/journal/v22/n2/full/2405062a.html Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma] [https://www.ncbi.nlm.nih.gov/pubmed/18094721 PubMed] | ||
==ITAC-CME== | ==ITAC-CME== | ||
+ | |||
*'''2016:''' [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30369-2/fulltext International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer] [https://www.ncbi.nlm.nih.gov/pubmed/27733271 PubMed] | *'''2016:''' [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30369-2/fulltext International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer] [https://www.ncbi.nlm.nih.gov/pubmed/27733271 PubMed] | ||
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|} | |} | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
− | !style="width: 20%"|Study | + | ! style="width: 20%" |Study |
− | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: 20%"|Comparator | + | ! style="width: 20%" |Comparator |
− | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | + | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | !style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | + | ! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] |
|- | |- | ||
|[https://www.nejm.org/doi/10.1056/NEJMoa0810773 Lassen et al. 2009 (ADVANCE-1)]] | |[https://www.nejm.org/doi/10.1056/NEJMoa0810773 Lassen et al. 2009 (ADVANCE-1)]] | ||
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|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*Total knee replacement | *Total knee replacement | ||
+ | |||
====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''' | ||
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|} | |} | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
− | !style="width: 20%"|Study | + | ! style="width: 20%" |Study |
− | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: 20%"|Comparator | + | ! style="width: 20%" |Comparator |
− | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | + | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | !style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | + | ! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] |
|- | |- | ||
|[https://www.nejm.org/doi/10.1056/NEJMoa1006885 Lassen et al. 2010 (ADVANCE-3)] | |[https://www.nejm.org/doi/10.1056/NEJMoa1006885 Lassen et al. 2010 (ADVANCE-3)] | ||
Line 111: | Line 125: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*Total hip replacement | *Total hip replacement | ||
+ | |||
====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''' | ||
Line 123: | Line 140: | ||
|} | |} | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
− | !style="width: 20%"|Study | + | ! style="width: 20%" |Study |
− | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: 20%"|Comparator | + | ! style="width: 20%" |Comparator |
− | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | + | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | !style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | + | ! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] |
|- | |- | ||
|[https://www.nejm.org/doi/full/10.1056/NEJMoa1814468 Carrier et al. 2018 (AVERT)] | |[https://www.nejm.org/doi/full/10.1056/NEJMoa1814468 Carrier et al. 2018 (AVERT)] | ||
Line 137: | Line 154: | ||
|} | |} | ||
====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''' | ||
===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://www.nejm.org/doi/10.1056/NEJMoa0810773 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19657123 PubMed] | + | |
− | # '''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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)62125-5/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20206776 PubMed] | + | #'''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://www.nejm.org/doi/10.1056/NEJMoa0810773 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19657123 PubMed] |
− | # '''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://www.nejm.org/doi/10.1056/NEJMoa1006885 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21175312 PubMed] | + | #'''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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)62125-5/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20206776 PubMed] |
− | # '''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://www.nejm.org/doi/full/10.1056/NEJMoa1814468 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30511879 PubMed] | + | #'''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://www.nejm.org/doi/10.1056/NEJMoa1006885 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21175312 PubMed] |
+ | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa1814468 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30511879 PubMed] | ||
==Aspirin monotherapy {{#subobject:2b1389|Regimen=1}}== | ==Aspirin monotherapy {{#subobject:2b1389|Regimen=1}}== | ||
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|} | |} | ||
====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''' | ||
===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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(00)02110-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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://www.nejm.org/doi/full/10.1056/NEJMoa035572 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/14711910 PubMed] | + | #'''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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(00)02110-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10776741 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://ascopubs.org/doi/full/10.1200/JCO.2010.31.6844 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21282540 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://www.nejm.org/doi/full/10.1056/NEJMoa035572 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/14711910 PubMed] |
− | # 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. [http://www.bloodjournal.org/content/119/4/933.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21835953 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://ascopubs.org/doi/full/10.1200/JCO.2010.31.6844 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21282540 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. [http://annals.org/aim/fullarticle/1692573/aspirin-versus-low-molecular-weight-heparin-extended-venous-thromboembolism-prophylaxis link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23732713 PubMed] | + | #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. [http://www.bloodjournal.org/content/119/4/933.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21835953 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://www.nejm.org/doi/full/10.1056/NEJMoa1712746 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29466159 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. [http://annals.org/aim/fullarticle/1692573/aspirin-versus-low-molecular-weight-heparin-extended-venous-thromboembolism-prophylaxis link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23732713 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://www.nejm.org/doi/full/10.1056/NEJMoa1712746 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29466159 PubMed] | ||
==Betrixaban monotherapy {{#subobject:834d5c|Regimen=1}}== | ==Betrixaban monotherapy {{#subobject:834d5c|Regimen=1}}== | ||
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''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.'' | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
+ | |||
*[[Betrixaban (Bevyxxa)]] 80 mg PO once per day | *[[Betrixaban (Bevyxxa)]] 80 mg PO once per day | ||
+ | |||
===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://www.nejm.org/doi/full/10.1056/NEJMoa1601747 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27232649 PubMed] | + | |
+ | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa1601747 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27232649 PubMed] | ||
==Enoxaparin monotherapy {{#subobject:f7bdac|Regimen=1}}== | ==Enoxaparin monotherapy {{#subobject:f7bdac|Regimen=1}}== | ||
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! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Toxicity]] | ! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Toxicity]] | ||
|- | |- | ||
− | |[https://www.nejm.org/doi/full/10.1056/NEJM199609053351003 Geerts et al. 1996] | + | |[https://www.nejm.org/doi/full/10.1056/NEJM199609053351003 Geerts et al. 1996] |
| style="background-color:#1a9851" |Phase III (E) | | style="background-color:#1a9851" |Phase III (E) | ||
|UFH | |UFH | ||
Line 252: | Line 276: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*Total knee replacement (ADVANCE-1) | *Total knee replacement (ADVANCE-1) | ||
*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. | ||
+ | |||
====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 | + | |
− | *The comparison arm in Geerts et al. used heparin 5000 units subcutaneous every 12 hours. | + | *[[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. | ||
===Variant #2, 40 mg daily {{#subobject:8e940e|Variant=1}}=== | ===Variant #2, 40 mg daily {{#subobject:8e940e|Variant=1}}=== | ||
Line 338: | Line 365: | ||
''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.'' | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*ADVANCE-2: Total knee replacement | *ADVANCE-2: Total knee replacement | ||
*ADVANCE-3: Total hip replacement | *ADVANCE-3: Total hip replacement | ||
+ | |||
====Anticoagulation==== | ====Anticoagulation==== | ||
+ | |||
*[[Enoxaparin (Lovenox)]] 40 mg SC once per day | *[[Enoxaparin (Lovenox)]] 40 mg SC once per day | ||
Line 346: | Line 376: | ||
===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://www.nejm.org/doi/full/10.1056/NEJM199609053351003 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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://www.nejm.org/doi/full/10.1056/NEJM199909093411103 link to original article]. [https://www.ncbi.nlm.nih.gov/pubmed/10477777 PubMed]. | + | #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://www.nejm.org/doi/full/10.1056/NEJM199609053351003 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8703169 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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)60880-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18582928 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://www.nejm.org/doi/full/10.1056/NEJM199909093411103 link to original article]. [https://www.ncbi.nlm.nih.gov/pubmed/10477777 PubMed]. |
− | # '''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://www.nejm.org/doi/full/10.1056/NEJMoa0800374 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18579811 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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)60880-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18582928 PubMed] |
− | # '''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://www.nejm.org/doi/full/10.1056/NEJMoa076016 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18579812 PubMed] | + | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa0800374 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18579811 PubMed] |
− | # '''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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60734-0/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19411100 PubMed] | + | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa076016 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18579812 PubMed] |
− | # '''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://www.nejm.org/doi/10.1056/NEJMoa0810773 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19657123 PubMed] | + | #'''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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60734-0/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19411100 PubMed] |
− | # '''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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)62125-5/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20206776 PubMed] | + | #'''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://www.nejm.org/doi/10.1056/NEJMoa0810773 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19657123 PubMed] |
− | # '''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. [http://annals.org/aim/fullarticle/745859/extended-duration-venous-thromboembolism-prophylaxis-acutely-ill-medical-patients-recently link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20621900 PubMed] | + | #'''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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)62125-5/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20206776 PubMed] |
− | # '''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://www.nejm.org/doi/10.1056/NEJMoa1006885 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21175312 PubMed] | + | #'''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. [http://annals.org/aim/fullarticle/745859/extended-duration-venous-thromboembolism-prophylaxis-acutely-ill-medical-patients-recently link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20621900 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://ascopubs.org/doi/full/10.1200/JCO.2010.31.6844 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21282540 PubMed] | + | #'''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://www.nejm.org/doi/10.1056/NEJMoa1006885 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21175312 PubMed] |
− | # 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. [http://www.bloodjournal.org/content/119/4/933.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21835953 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://ascopubs.org/doi/full/10.1200/JCO.2010.31.6844 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21282540 PubMed] |
− | # '''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://www.nejm.org/doi/10.1056/NEJMoa1110899 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22077144 PubMed] | + | #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. [http://www.bloodjournal.org/content/119/4/933.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21835953 PubMed] |
− | # '''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://www.nejm.org/doi/10.1056/NEJMoa1111288 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22204723 PubMed] | + | #'''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://www.nejm.org/doi/10.1056/NEJMoa1110899 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22077144 PubMed] |
− | # '''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://www.nejm.org/doi/full/10.1056/NEJMoa1111096 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23388003 PubMed] | + | #'''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://www.nejm.org/doi/10.1056/NEJMoa1111288 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22204723 PubMed] |
− | # '''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://www.nejm.org/doi/full/10.1056/NEJMoa1601747 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27232649 PubMed] | + | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa1111096 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23388003 PubMed] |
+ | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa1601747 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27232649 PubMed] | ||
==Placebo== | ==Placebo== | ||
Line 399: | Line 430: | ||
''No active treatment.'' | ''No active treatment.'' | ||
===References=== | ===References=== | ||
− | # Gärdlund B; The Heparin Prophylaxis Study Group. Randomised, controlled trial of low-dose heparin for prevention of fatal pulmonary embolism in patients with infectious diseases. Lancet. 1996 May 18;347(9012):1357-61. [https://www.sciencedirect.com/science/article/pii/S0140673696910090 link to SD article] [https://www.ncbi.nlm.nih.gov/pubmed/8637340 PubMed] | + | |
− | # '''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. [http://annals.org/aim/fullarticle/745859/extended-duration-venous-thromboembolism-prophylaxis-acutely-ill-medical-patients-recently link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20621900 PubMed] | + | #Gärdlund B; The Heparin Prophylaxis Study Group. Randomised, controlled trial of low-dose heparin for prevention of fatal pulmonary embolism in patients with infectious diseases. Lancet. 1996 May 18;347(9012):1357-61. [https://www.sciencedirect.com/science/article/pii/S0140673696910090 link to SD article] [https://www.ncbi.nlm.nih.gov/pubmed/8637340 PubMed] |
− | # '''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://www.nejm.org/doi/10.1056/NEJMoa1111288 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22204723 PubMed] | + | #'''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. [http://annals.org/aim/fullarticle/745859/extended-duration-venous-thromboembolism-prophylaxis-acutely-ill-medical-patients-recently link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20621900 PubMed] |
− | # '''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://www.nejm.org/doi/10.1056/NEJMoa1805090 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30145946 PubMed] | + | #'''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://www.nejm.org/doi/10.1056/NEJMoa1111288 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22204723 PubMed] |
− | # '''CASSINI:''' Khorana AA, Soff GA, Kakkar AK, Vadhan-Raj S, Riess H, Wun T, Streiff MB, Garcia DA, Liebman HA, Belani CP, O'Reilly EM, Patel JN, Yimer HA, Wildgoose P, Burton P, Vijapurkar U, Kaul S, Eikelboom J, McBane R, Bauer KA, Kuderer NM, Lyman GH; CASSINI Investigators. Rivaroxaban for thromboprophylaxis in high-risk ambulatory patients with cancer. N Engl J Med. 2019 Feb 21;380(8):720-728. [https://www.nejm.org/doi/full/10.1056/NEJMoa1814630 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30786186 PubMed] | + | #'''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://www.nejm.org/doi/10.1056/NEJMoa1805090 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30145946 PubMed] |
+ | #'''CASSINI:''' Khorana AA, Soff GA, Kakkar AK, Vadhan-Raj S, Riess H, Wun T, Streiff MB, Garcia DA, Liebman HA, Belani CP, O'Reilly EM, Patel JN, Yimer HA, Wildgoose P, Burton P, Vijapurkar U, Kaul S, Eikelboom J, McBane R, Bauer KA, Kuderer NM, Lyman GH; CASSINI Investigators. Rivaroxaban for thromboprophylaxis in high-risk ambulatory patients with cancer. N Engl J Med. 2019 Feb 21;380(8):720-728. [https://www.nejm.org/doi/full/10.1056/NEJMoa1814630 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30786186 PubMed] | ||
==Rivaroxaban monotherapy {{#subobject:6a7fba|Regimen=1}}== | ==Rivaroxaban monotherapy {{#subobject:6a7fba|Regimen=1}}== | ||
Line 454: | Line 486: | ||
|} | |} | ||
====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) | ||
+ | |||
===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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)60880-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18582928 PubMed] | + | |
− | # '''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://www.nejm.org/doi/full/10.1056/NEJMoa0800374 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18579811 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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)60880-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18582928 PubMed] |
− | # '''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://www.nejm.org/doi/full/10.1056/NEJMoa076016 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18579812 PubMed] | + | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa0800374 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18579811 PubMed] |
− | # '''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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60734-0/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19411100 PubMed] | + | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa076016 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18579812 PubMed] |
− | # '''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://www.nejm.org/doi/full/10.1056/NEJMoa1111096 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23388003 PubMed] | + | #'''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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60734-0/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19411100 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://www.nejm.org/doi/full/10.1056/NEJMoa1712746 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29466159 PubMed] | + | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa1111096 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23388003 PubMed] |
− | # '''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://www.nejm.org/doi/10.1056/NEJMoa1805090 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30145946 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://www.nejm.org/doi/full/10.1056/NEJMoa1712746 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29466159 PubMed] |
+ | #'''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://www.nejm.org/doi/10.1056/NEJMoa1805090 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30145946 PubMed] | ||
=VTE secondary prevention= | =VTE secondary prevention= | ||
Line 476: | Line 511: | ||
|} | |} | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
− | !style="width: 25%"|Study | + | ! style="width: 25%" |Study |
− | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: 25%"|Comparator | + | ! style="width: 25%" |Comparator |
− | !style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
|- | |- | ||
| rowspan="2" |[https://www.nejm.org/doi/full/10.1056/NEJMoa1207541 Agnelli et al. 2012 (AMPLIFY-EXT)] | | rowspan="2" |[https://www.nejm.org/doi/full/10.1056/NEJMoa1207541 Agnelli et al. 2012 (AMPLIFY-EXT)] | ||
Line 491: | Line 526: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*Therapeutic anticoagulation x 6-12 mo | *Therapeutic anticoagulation x 6-12 mo | ||
+ | |||
====Anticoagulation==== | ====Anticoagulation==== | ||
+ | |||
*[[Apixaban (Eliquis)]] 2.5 mg PO twice per day | *[[Apixaban (Eliquis)]] 2.5 mg PO twice per day | ||
Line 499: | Line 537: | ||
===Variant #2, 5 mg twice per day {{#subobject:c7bfff0|Variant=1}}=== | ===Variant #2, 5 mg twice per day {{#subobject:c7bfff0|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
− | !style="width: 25%"|Study | + | ! style="width: 25%" |Study |
− | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: 25%"|Comparator | + | ! style="width: 25%" |Comparator |
− | !style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
|- | |- | ||
| rowspan="2" |[https://www.nejm.org/doi/full/10.1056/NEJMoa1207541 Agnelli et al. 2012 (AMPLIFY-EXT)] | | rowspan="2" |[https://www.nejm.org/doi/full/10.1056/NEJMoa1207541 Agnelli et al. 2012 (AMPLIFY-EXT)] | ||
Line 514: | Line 552: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*Therapeutic anticoagulation x 6-12 mo | *Therapeutic anticoagulation x 6-12 mo | ||
+ | |||
====Anticoagulation==== | ====Anticoagulation==== | ||
+ | |||
*[[Apixaban (Eliquis)]] 5 mg PO twice per day | *[[Apixaban (Eliquis)]] 5 mg PO twice per day | ||
Line 521: | Line 562: | ||
===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://www.nejm.org/doi/full/10.1056/NEJMoa1207541 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23216615 PubMed] | + | |
+ | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa1207541 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23216615 PubMed] | ||
==Aspirin monotherapy {{#subobject:eb5633|Regimen=1}}== | ==Aspirin monotherapy {{#subobject:eb5633|Regimen=1}}== | ||
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''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.'' | ||
====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 | ||
+ | |||
====Anticoagulation==== | ====Anticoagulation==== | ||
+ | |||
*[[Aspirin]] 100 mg PO once per day | *[[Aspirin]] 100 mg PO once per day | ||
Line 559: | Line 604: | ||
===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://www.nejm.org/doi/full/10.1056/NEJMoa1114238 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22621626 PubMed] | + | |
− | # '''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://www.nejm.org/doi/full/10.1056/NEJMoa1210384 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23121403 PubMed] | + | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa1114238 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22621626 PubMed] |
+ | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa1210384 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23121403 PubMed] | ||
==Dalteparin monotherapy {{#subobject:57c5b7|Regimen=1}}== | ==Dalteparin monotherapy {{#subobject:57c5b7|Regimen=1}}== | ||
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|} | |} | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
+ | |||
*[[Dalteparin (Fragmin)]] as follows: | *[[Dalteparin (Fragmin)]] as follows: | ||
**'''Month 1:''' 200 IU/kg SC once per day | **'''Month 1:''' 200 IU/kg SC once per day | ||
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'''6-month course''' | '''6-month course''' | ||
===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://www.nejm.org/doi/full/10.1056/NEJMoa025313 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12853587 PubMed] | + | |
− | ## '''Posthoc 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. [http://jco.ascopubs.org/content/23/10/2123.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15699480 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://www.nejm.org/doi/full/10.1056/NEJMoa025313 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12853587 PubMed] |
+ | ##'''Posthoc 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. [http://jco.ascopubs.org/content/23/10/2123.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15699480 PubMed] | ||
==Enoxaparin monotherapy {{#subobject:30d50d|Regimen=1}}== | ==Enoxaparin monotherapy {{#subobject:30d50d|Regimen=1}}== | ||
Line 611: | Line 659: | ||
|} | |} | ||
====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''' | ||
===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.jamanetwork.com/article.aspx?articleid=754085 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12153376 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://archinte.jamanetwork.com/article.aspx?articleid=754085 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12153376 PubMed] | ||
==Warfarin monotherapy {{#subobject:acc688|Regimen=1}}== | ==Warfarin monotherapy {{#subobject:acc688|Regimen=1}}== | ||
Line 644: | Line 694: | ||
|} | |} | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
+ | |||
*[[Warfarin (Coumadin)]] PO titrated to goal INR 2.0 to 3.0 | *[[Warfarin (Coumadin)]] PO titrated to goal INR 2.0 to 3.0 | ||
Line 662: | Line 713: | ||
|} | |} | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
+ | |||
*Warfarin with goal INR of 2.0 to 3.0 for median of 6.5 mo | *Warfarin with goal INR of 2.0 to 3.0 for median of 6.5 mo | ||
+ | |||
====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 | ||
Line 669: | Line 723: | ||
===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.jamanetwork.com/article.aspx?articleid=754085 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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://www.nejm.org/doi/full/10.1056/NEJMoa035029 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12601075 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://archinte.jamanetwork.com/article.aspx?articleid=754085 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12153376 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://www.nejm.org/doi/full/10.1056/NEJMoa025313 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12853587 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://www.nejm.org/doi/full/10.1056/NEJMoa035029 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12601075 PubMed] |
− | ## '''Posthoc 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. [http://jco.ascopubs.org/content/23/10/2123.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15699480 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://www.nejm.org/doi/full/10.1056/NEJMoa025313 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12853587 PubMed] |
+ | ##'''Posthoc 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. [http://jco.ascopubs.org/content/23/10/2123.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15699480 PubMed] | ||
=VTE treatment, all lines of therapy= | =VTE treatment, all lines of therapy= | ||
Line 700: | Line 755: | ||
|} | |} | ||
====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 | ||
Line 705: | Line 761: | ||
===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://www.nejm.org/doi/full/10.1056/NEJMoa1302507 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23808982 PubMed] | + | |
+ | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa1302507 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23808982 PubMed] | ||
==Argatroban monotherapy {{#subobject:8171b3|Regimen=1}}== | ==Argatroban monotherapy {{#subobject:8171b3|Regimen=1}}== | ||
Line 714: | Line 771: | ||
===Regimen {{#subobject:3f6d7f|Variant=1}}=== | ===Regimen {{#subobject:3f6d7f|Variant=1}}=== | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
+ | |||
*[[Argatroban (Acova)]] | *[[Argatroban (Acova)]] | ||
+ | |||
===References=== | ===References=== | ||
To be completed | To be completed | ||
Line 743: | Line 802: | ||
|} | |} | ||
====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 | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
− | *[[Aspirin]] 100 mg PO once per day | + | |
+ | *[[Aspirin]] 100 mg PO once per day | ||
'''Up to 12-month course''' | '''Up to 12-month course''' | ||
===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://www.nejm.org/doi/full/10.1056/NEJMoa1700518 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28316279 PubMed] | + | |
+ | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa1700518 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28316279 PubMed] | ||
==Bivalirudin monotherapy {{#subobject:5a08f6|Regimen=1}}== | ==Bivalirudin monotherapy {{#subobject:5a08f6|Regimen=1}}== | ||
Line 759: | Line 821: | ||
===Regimen {{#subobject:5faf02|Variant=1}}=== | ===Regimen {{#subobject:5faf02|Variant=1}}=== | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
+ | |||
*[[Bivalirudin (Angiomax)]] | *[[Bivalirudin (Angiomax)]] | ||
+ | |||
===References=== | ===References=== | ||
To be completed | To be completed | ||
Line 784: | Line 848: | ||
|} | |} | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
+ | |||
*[[Dabigatran (Pradaxa)]] 150 mg PO twice per day | *[[Dabigatran (Pradaxa)]] 150 mg PO twice per day | ||
'''6-month course''' | '''6-month course''' | ||
===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://www.nejm.org/doi/full/10.1056/NEJMoa0906598 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19966341 PubMed] | + | |
− | # '''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://www.nejm.org/doi/full/10.1056/NEJMoa1113697 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23425163 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa0906598 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19966341 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. [http://circ.ahajournals.org/content/129/7/764.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24344086 PubMed] | + | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa1113697 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23425163 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. [http://circ.ahajournals.org/content/129/7/764.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24344086 PubMed] | ||
==Dalteparin monotherapy {{#subobject:4a96a1|Regimen=1}}== | ==Dalteparin monotherapy {{#subobject:4a96a1|Regimen=1}}== | ||
Line 825: | Line 891: | ||
|} | |} | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
+ | |||
*[[Dalteparin (Fragmin)]] as follows: | *[[Dalteparin (Fragmin)]] as follows: | ||
**First month: 200 IU/kg once per day | **First month: 200 IU/kg once per day | ||
Line 831: | Line 898: | ||
'''6- to 12-month course''' | '''6- to 12-month course''' | ||
===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://onlinelibrary.wiley.com/doi/10.1111/jth.12923/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25827941 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://www.nejm.org/doi/full/10.1056/NEJMoa1711948 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29231094 PubMed] | + | #'''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://onlinelibrary.wiley.com/doi/10.1111/jth.12923/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25827941 PubMed] |
− | # '''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://ascopubs.org/doi/full/10.1200/JCO.2018.78.8034 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29746227 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://www.nejm.org/doi/full/10.1056/NEJMoa1711948 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29231094 PubMed] |
+ | #'''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://ascopubs.org/doi/full/10.1200/JCO.2018.78.8034 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29746227 PubMed] | ||
==Edoxaban monotherapy {{#subobject:d0ebe7|Regimen=1}}== | ==Edoxaban monotherapy {{#subobject:d0ebe7|Regimen=1}}== | ||
Line 863: | Line 931: | ||
''Note: this dose was used for patients with CrCl of 30 to 50 mL/min/1.73m<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]].'' | ''Note: this dose was used for patients with CrCl of 30 to 50 mL/min/1.73m<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]].'' | ||
====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)]] 30 mg PO once per day | *[[Edoxaban (Savaysa)]] 30 mg PO once per day | ||
Line 890: | Line 959: | ||
|} | |} | ||
====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 | ||
Line 895: | Line 965: | ||
'''3- to 12-month course''' | '''3- to 12-month course''' | ||
===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://www.nejm.org/doi/full/10.1056/NEJMoa1306638 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23991658 PubMed] | + | |
− | ## '''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://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(16)30057-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27476789 PubMed] | + | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa1306638 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23991658 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://www.nejm.org/doi/full/10.1056/NEJMoa1711948 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29231094 PubMed] | + | ##'''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://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(16)30057-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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://www.nejm.org/doi/full/10.1056/NEJMoa1711948 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29231094 PubMed] | ||
==Enoxaparin monotherapy {{#subobject:fc9e30|Regimen=1}}== | ==Enoxaparin monotherapy {{#subobject:fc9e30|Regimen=1}}== | ||
Line 918: | Line 989: | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
+ | |||
*[[Enoxaparin (Lovenox)]] SC 100 IU/kg every 12 hours | *[[Enoxaparin (Lovenox)]] SC 100 IU/kg every 12 hours | ||
+ | |||
===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 Aug23;296(8):935-42. [https://jamanetwork.com/journals/jama/fullarticle/203221 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16926353 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 Aug23;296(8):935-42. [https://jamanetwork.com/journals/jama/fullarticle/203221 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16926353 PubMed] | ||
==Fondaparinux monotherapy {{#subobject:7a8cb8|Regimen=1}}== | ==Fondaparinux monotherapy {{#subobject:7a8cb8|Regimen=1}}== | ||
Line 929: | Line 1,003: | ||
===Regimen {{#subobject:ab5c25|Variant=1}}=== | ===Regimen {{#subobject:ab5c25|Variant=1}}=== | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
+ | |||
*[[Fondaparinux (Arixtra)]] | *[[Fondaparinux (Arixtra)]] | ||
+ | |||
===References=== | ===References=== | ||
To be completed | To be completed | ||
Line 957: | Line 1,033: | ||
''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.'' | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
+ | |||
*[[Unfractionated heparin (UFH)]] SC 333 units/kg once, then 250 units/kg every 12 hours | *[[Unfractionated heparin (UFH)]] SC 333 units/kg once, then 250 units/kg every 12 hours | ||
===References=== | ===References=== | ||
− | # Loewe L, Hirsch E. Heparin in the treatment of thromboembolic disease. JAMA. 1947;133(17):1263-1268. [https://jamanetwork.com/journals/jama/article-abstract/293153 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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 Aug23;296(8):935-42. [https://jamanetwork.com/journals/jama/fullarticle/203221 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16926353 PubMed] | + | #Loewe L, Hirsch E. Heparin in the treatment of thromboembolic disease. JAMA. 1947;133(17):1263-1268. [https://jamanetwork.com/journals/jama/article-abstract/293153 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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 Aug23;296(8):935-42. [https://jamanetwork.com/journals/jama/fullarticle/203221 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16926353 PubMed] | ||
==Lepirudin monotherapy {{#subobject:b61e00|Regimen=1}}== | ==Lepirudin monotherapy {{#subobject:b61e00|Regimen=1}}== | ||
Line 970: | Line 1,048: | ||
===Regimen {{#subobject:22918f|Variant=1}}=== | ===Regimen {{#subobject:22918f|Variant=1}}=== | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
+ | |||
*[[Lepirudin (Refludan)]] | *[[Lepirudin (Refludan)]] | ||
+ | |||
===References=== | ===References=== | ||
To be completed | To be completed | ||
Line 999: | Line 1,079: | ||
|} | |} | ||
====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 | ||
+ | |||
====Anticoagulation==== | ====Anticoagulation==== | ||
+ | |||
*[[Rivaroxaban (Xarelto)]] 10 mg PO once per day | *[[Rivaroxaban (Xarelto)]] 10 mg PO once per day | ||
Line 1,025: | Line 1,108: | ||
|} | |} | ||
====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 | ||
+ | |||
====Anticoagulation==== | ====Anticoagulation==== | ||
+ | |||
*[[Rivaroxaban (Xarelto)]] 20 mg PO once per day | *[[Rivaroxaban (Xarelto)]] 20 mg PO once per day | ||
Line 1,059: | Line 1,145: | ||
|} | |} | ||
====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 | ||
Line 1,064: | Line 1,151: | ||
===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://www.nejm.org/doi/full/10.1056/NEJMoa1007903 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21128814 PubMed] | + | |
− | # '''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://www.nejm.org/doi/full/10.1056/NEJMoa1113572 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22449293 PubMed] | + | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa1007903 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21128814 PubMed] |
− | # '''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://www.thelancet.com/journals/lanhae/article/PIIS2352-3026%2815%2900257-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26765643 PubMed] | + | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa1113572 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22449293 PubMed] |
− | # '''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://www.nejm.org/doi/full/10.1056/NEJMoa1700518 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28316279 PubMed] | + | #'''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://www.thelancet.com/journals/lanhae/article/PIIS2352-3026%2815%2900257-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26765643 PubMed] |
− | # '''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://ascopubs.org/doi/full/10.1200/JCO.2018.78.8034 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29746227 PubMed] | + | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa1700518 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28316279 PubMed] |
+ | #'''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://ascopubs.org/doi/full/10.1200/JCO.2018.78.8034 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29746227 PubMed] | ||
==Tinzaparin monotherapy {{#subobject:3d9d84|Regimen=1}}== | ==Tinzaparin monotherapy {{#subobject:3d9d84|Regimen=1}}== | ||
Line 1,078: | Line 1,166: | ||
''Note: this agent has been withdrawn from the US market.'' | ''Note: this agent has been withdrawn from the US market.'' | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
+ | |||
*[[Tinzaparin (Innohep)]] | *[[Tinzaparin (Innohep)]] | ||
+ | |||
===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://www.amjmed.com/article/S0002-9343(06)00263-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://jama.jamanetwork.com/article.aspx?articleid=2428955 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26284719 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://www.amjmed.com/article/S0002-9343(06)00263-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://jama.jamanetwork.com/article.aspx?articleid=2428955 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26284719 PubMed] | ||
==Warfarin monotherapy {{#subobject:76610c|Regimen=1}}== | ==Warfarin monotherapy {{#subobject:76610c|Regimen=1}}== | ||
Line 1,128: | Line 1,219: | ||
|} | |} | ||
====Anticoagulation==== | ====Anticoagulation==== | ||
+ | |||
*[[Warfarin (Coumadin)]] with goal INR between 2.0 and 3.0 | *[[Warfarin (Coumadin)]] with goal INR between 2.0 and 3.0 | ||
+ | |||
====Supportive medications==== | ====Supportive medications==== | ||
+ | |||
*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 every 12 hours until INR greater than 2.0 | ||
'''3-, 6-, or 12- month course (see individual papers)''' | '''3-, 6-, or 12- month course (see individual papers)''' | ||
===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://www.amjmed.com/article/S0002-9343(06)00263-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17145251 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa0906598 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19966341 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://www.amjmed.com/article/S0002-9343(06)00263-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17145251 PubMed] |
− | # '''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://www.nejm.org/doi/full/10.1056/NEJMoa1007903 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21128814 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa0906598 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19966341 PubMed] |
− | # '''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://www.nejm.org/doi/full/10.1056/NEJMoa1113572 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22449293 PubMed] | + | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa1007903 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21128814 PubMed] |
− | # '''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://www.nejm.org/doi/full/10.1056/NEJMoa1113697 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23425163 PubMed] | + | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa1113572 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22449293 PubMed] |
− | # '''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://www.nejm.org/doi/full/10.1056/NEJMoa1302507 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23808982 PubMed] | + | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa1113697 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23425163 PubMed] |
− | # '''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://www.nejm.org/doi/full/10.1056/NEJMoa1306638 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23991658 PubMed] | + | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa1302507 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23808982 PubMed] |
− | ## '''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://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(16)30057-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27476789 PubMed] | + | #'''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://www.nejm.org/doi/full/10.1056/NEJMoa1306638 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23991658 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. [http://circ.ahajournals.org/content/129/7/764.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24344086 PubMed] | + | ##'''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://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(16)30057-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27476789 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. [http://jama.jamanetwork.com/article.aspx?articleid=2428955 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26284719 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. [http://circ.ahajournals.org/content/129/7/764.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24344086 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. [http://jama.jamanetwork.com/article.aspx?articleid=2428955 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26284719 PubMed] | ||
=Additional information= | =Additional information= | ||
<references /> | <references /> | ||
+ | |||
*[http://journal.publications.chestnet.org/data/Journals/CHEST/934919/11026.pdf ACCP Chest guidelines for antithrombotic therapy for venous thromboembolic disease (2016)] | *[http://journal.publications.chestnet.org/data/Journals/CHEST/934919/11026.pdf ACCP Chest guidelines for antithrombotic therapy for venous thromboembolic disease (2016)] | ||
*[http://journal.publications.chestnet.org/issue.aspx?journalid=99&issueid=23443&direction=P ACCP Chest Guidelines (2012)] - Antithrombotic Therapy and Prevention of Thrombosis, 9th edition (2012) | *[http://journal.publications.chestnet.org/issue.aspx?journalid=99&issueid=23443&direction=P ACCP Chest Guidelines (2012)] - Antithrombotic Therapy and Prevention of Thrombosis, 9th edition (2012) |
Revision as of 16:00, 6 August 2019
Section editors | |||
---|---|---|---|
Shruti Chaturvedi, MBBS, MSCI Johns Hopkins University Baltimore, MD |
Benjamin Tillman, MD Vanderbilt University Nashville, TN |
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).
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
|
Guidelines
ACCP
ASCO
- 2019: Key et al. Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update. PubMed
Older
- 2015: Lyman et al. ASCO Clinical Practice Guideline on VTE prophylaxis and treatment 2014 update
- 2013: Lyman et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update PubMed
- 2013: Lyman et al. ASCO Clinical Practice Guideline on VTE prophylaxis and treatment 2013 update PubMed
ASH
- 2018: Schünemann et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients
- 2018: Lim et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: diagnosis of venous thromboembolism
- 2018: Witt et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy
- 2018: Monagle et al. American Society of Hematology 2018 Guidelines for management of venous thromboembolism: treatment of pediatric venous thromboembolism
- 2018: Bates et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy
- 2018: Cuker et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia
ESMO
- 2010: Venous thromboembolism (VTE) in cancer patients. ESMO clinical recommendations for prevention and management PubMed
IMWG
Current
- 2010: IMWG guidelines for the prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma
Older
ITAC-CME
- 2016: International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer PubMed
VTE primary prophylaxis
Apixaban monotherapy
back to top |
Variant #1, 10-14 days post-op
FDA-recommended dose |
Study | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|
Lassen et al. 2009 (ADVANCE-1)] | Phase III (E) | Enoxaparin | Seems not superior | Seems to have lower bleeding rate |
Lassen et al. 2010 (ADVANCE-2) | Phase III (E) | Enoxaparin | Superior composite 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
Variant #2, 35 days post-op
FDA-recommended dose |
Study | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|
Lassen et al. 2010 (ADVANCE-3) | Phase III (E) | Enoxaparin | Superior composite endpoint | Seems not superior |
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
Variant #3, 180 days
FDA-recommended dose |
Study | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|
Carrier et al. 2018 (AVERT) | Phase III (E) | Placebo | Superior VTE rate | 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 contains protocol PubMed
- 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 contains protocol PubMed
- 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
- 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 contains verified protocol PubMed
Aspirin monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Rodgers et al. 2000 (PEP) | Phase III (E) | Placebo | Superior VTE rate |
Landolfi et al. 2004 (ECLAP) | Phase III (E) | Placebo | Seems to have superior rate of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes |
Palumbo et al. 2011 | Phase III (E) | 1. Enoxaparin 2. Low-dose warfarin |
Seems not superior |
Larocca et al. 2011 | Phase III (E) | Enoxaparin | Seems not superior |
Anderson et al. 2013 (EPCAT) | Phase III (E) | Dalteparin | Non-inferior VTE rate at 90 days |
Anderson et al. 2018 (EPCAT II) | Phase III (E) | Rivaroxaban | Non-inferior VTE rate at 90 days |
Anticoagulation
- Aspirin 81 to 160 mg PO once per day
Various durations, see individual trials
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
- 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
- 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
- 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
- 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
Betrixaban monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Cohen et al. 2016 (APEX-VTE) | Phase III (E) | Enoxaparin | Might have lower rates of VTE |
Note: this APEX trial should not be confused with the one in multiple myeloma.
Anticoagulation
- Betrixaban (Bevyxxa) 80 mg PO once per day
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. link to original article PubMed
Enoxaparin monotherapy
back to top |
Variant #1, 30 mg every 12 hours
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Geerts et al. 1996 | Phase III (E) | UFH | Superior DVT rates | No difference in major bleeding rate |
Lassen et al. 2009 (ADVANCE-1)] | Phase III (C) | Apixaban | Seems not superior | Seems to have higher bleeding rate |
Preceding treatment
- Total knee replacement (ADVANCE-1)
- 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.
Variant #2, 40 mg daily
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Samama et al. 1999 (MEDENOX) | Phase III (C) | 1. Placebo 2. Enoxaparin 20 mg daily |
Superior VTE rates |
Kakkar et al. 2008 (RECORD2) | Phase III (C) | Rivaroxaban | Inferior composite outcome |
Erikkson et al. 2008 (RECORD1) | Phase III (C) | Rivaroxaban | Inferior composite outcome |
Lassen et al. 2008 (RECORD3) | Phase III (C) | Rivaroxaban | Inferior composite outcome |
Turpie et al. 2009 (RECORD4) | Phase III (C) | Rivaroxaban | Seems to have inferior composite outcome |
Lassen et al. 2010 (ADVANCE-2) | Phase III (C) | Apixaban | Inferior composite outcome |
Hull et al. 2010 (EXCLAIM) | Phase III (E) | Placebo | Superior composite VTE rate |
Lassen et al. 2010 (ADVANCE-3) | Phase III (C) | Apixaban | Inferior composite outcome |
Palumbo et al. 2011 | Phase III (E) | 1. Aspirin 2. Low-dose warfarin |
Seems not superior |
Larocca et al. 2011 | Phase III (E) | Aspirin | Seems not superior |
Goldhaber et al. 2011 (ADOPT) | Phase III (C) | Apixaban | Seems not superior |
Kakkar et al. 2011 (LIFENOX) | Phase III (E) | Placebo | Seems not superior |
Cohen et al. 2013 (MAGELLAN) | Phase III (C) | Rivaroxaban | Non-inferior VTE rate at 10 days |
Cohen et al. 2016 (APEX-VTE) | Phase III (C) | Betrixaban | Might have higher rates of VTE |
Note: the APEX trial here should not be confused with the one in multiple myeloma.
Preceding treatment
- ADVANCE-2: Total knee replacement
- ADVANCE-3: Total hip replacement
Anticoagulation
- Enoxaparin (Lovenox) 40 mg SC once per day
Various durations (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
- 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
- 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
- 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
- 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 contains protocol PubMed
- 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 contains protocol PubMed
- 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
- 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 contains protocol 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. link to original article PubMed
- 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
- 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
- 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
- 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
- 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. link to original article PubMed
Placebo
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Gärdlund et al. 1996 | Phase III (C) | UFH (SC) | Seems not superior |
Hull et al. 2010 (EXCLAIM) | Phase III (C) | Enoxaparin | Inferior composite VTE rate |
Kakkar et al. 2011 (LIFENOX) | Phase III (C) | Enoxaparin | Seems not superior |
Spyropoulos et al. 2018 (MARINER) | Phase III (C) | Rivaroxaban | Seems not superior |
Khorana et al. 2019 (CASSINI) | Phase III (C) | Rivaroxaban | Seems not superior |
No active treatment.
References
- Gärdlund B; The Heparin Prophylaxis Study Group. Randomised, controlled trial of low-dose heparin for prevention of fatal pulmonary embolism in patients with infectious diseases. Lancet. 1996 May 18;347(9012):1357-61. link to SD article PubMed
- 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
- 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
- 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
- CASSINI: Khorana AA, Soff GA, Kakkar AK, Vadhan-Raj S, Riess H, Wun T, Streiff MB, Garcia DA, Liebman HA, Belani CP, O'Reilly EM, Patel JN, Yimer HA, Wildgoose P, Burton P, Vijapurkar U, Kaul S, Eikelboom J, McBane R, Bauer KA, Kuderer NM, Lyman GH; CASSINI Investigators. Rivaroxaban for thromboprophylaxis in high-risk ambulatory patients with cancer. N Engl J Med. 2019 Feb 21;380(8):720-728. link to original article PubMed
Rivaroxaban monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Kakkar et al. 2008 (RECORD2) | Phase III (E) | Enoxaparin | Superior composite outcome |
Erikkson et al. 2008 (RECORD1) | Phase III (E) | Enoxaparin | Superior composite outcome |
Lassen et al. 2008 (RECORD3) | Phase III (E) | Enoxaparin | Superior composite outcome |
Turpie et al. 2009 (RECORD4) | Phase III (E) | Enoxaparin | Seems to have superior composite outcome |
Cohen et al. 2013 (MAGELLAN) | Phase III (E) | Enoxaparin | Non-inferior VTE rate at 10 days |
Anderson et al. 2018 (EPCAT II) | Phase III (E) | Aspirin | Non-inferior VTE rate at 90 days |
Spyropoulos et al. 2018 (MARINER) | Phase III (E) | Placebo | Seems not superior |
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
- 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
- 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
- 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
- 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
- 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
- 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
VTE secondary prevention
Apixaban monotherapy
back to top |
Variant #1, 2.5 mg twice per day
FDA-recommended dose |
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Agnelli et al. 2012 (AMPLIFY-EXT) | Phase III (E) | 1. Apixaban 5 mg twice per day | Seems not superior |
2. Placebo | Superior composite endpoint |
Preceding treatment
- Therapeutic anticoagulation x 6-12 mo
Anticoagulation
- Apixaban (Eliquis) 2.5 mg PO twice per day
12-month course
Variant #2, 5 mg twice per day
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Agnelli et al. 2012 (AMPLIFY-EXT) | Phase III (E) | 1. Apixaban 2.5 mg twice per day | Seems not superior |
2. Placebo | Superior composite endpoint |
Preceding treatment
- Therapeutic anticoagulation x 6-12 mo
Anticoagulation
- Apixaban (Eliquis) 5 mg PO twice per day
12-month course
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 contains verified protocol PubMed
Aspirin monotherapy
back to top |
Regimen
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Becattini et al. 2012 (WARFASA) | Phase III (E) | Placebo | Superior rate of VTE recurrence | No difference in bleeding rate |
Brighton et al. 2012 (ASPIRE-VTE) | Phase III (E) | Placebo | Might have superior rate of VTE recurrence | No difference in bleeding rate |
Note: ASPIRE should not be confused with the multiple myeloma trial of the same name.
Preceding treatment
Anticoagulation
- Aspirin 100 mg PO once per day
Two or more years
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 contains protocol PubMed
- 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. link to original article PubMed
Dalteparin monotherapy
back to top |
Regimen
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Lee et al. 2003 (CLOT) | Phase III (E) | Warfarin | Superior rate of VTE at 6 months | 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
- Posthoc 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
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Meyer et al. 2002 | Phase III (E) | Warfarin | Might have superior combined VTE/bleeding outcome |
Anticoagulation
- Enoxaparin (Lovenox) 1.5 mg/kg SC once per day
3-month course
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 contains protocol PubMed
Warfarin monotherapy
back to top |
Variant #1, standard intensity
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Meyer et al. 2002 | Phase III (C) | Enoxaparin | Might have inferior combined VTE/bleeding outcome | |
Lee et al. 2003 (CLOT) | Phase III (C) | Dalteparin | Inferior rate of VTE at 6 months | No difference in bleeding rate |
Anticoagulation
- Warfarin (Coumadin) PO titrated to goal INR 2.0 to 3.0
Variant #2, low intensity
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Ridker et al. 2003 (PREVENT) | Phase III (E) | Placebo | Superior recurrent VTE rate | No difference in major bleeding |
Preceding treatment
- Warfarin with goal INR of 2.0 to 3.0 for median of 6.5 mo
Anticoagulation
- Warfarin (Coumadin) PO titrated to goal INR 1.5 to 2.0
Continued indefinitely
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
- 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 contains verified protocol 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
- Posthoc 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
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Regimen
FDA-recommended dose |
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Agnelli et al. 2013 (AMPLIFY) | Phase III (E) | Warfarin | Non-inferior composite endpoint | Lower rates of bleeding |
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 contains verified protocol PubMed
Argatroban monotherapy
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Regimen
Anticoagulation
References
To be completed
Aspirin monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Weitz et al. 2017 (EINSTEIN CHOICE) | Phase III (C) | 1. Rivaroxaban 10 mg | Inferior symptomatic recurrent VTE rate | Similar major bleeding |
2. Rivaroxaban 20 mg | Inferior symptomatic recurrent VTE rate | Similar major bleeding |
Preceding treatment
- 6 to 12 months of a vitamin K antagonist or a direct oral anticoagulant
Anticoagulation
- Aspirin 100 mg PO once per day
Up to 12-month course
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 contains verified protocol PubMed
Bivalirudin monotherapy
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Regimen
Anticoagulation
References
To be completed
Dabigatran monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Schulman et al. 2009 (RE-COVER) | Phase III (E) | Warfarin | Non-inferior composite endpoint | Similar major bleeding |
Anticoagulation
- Dabigatran (Pradaxa) 150 mg PO twice per day
6-month course
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 contains verified protocol PubMed
- 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
- 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
Dalteparin monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Francis et al. 2015 (DALTECAN) | Non-randomized | |||
Raskob et al. 2017 (Hokusai VTE Cancer) | Phase III (C) | Edoxaban | Non-inferior composite endpoint of VTE/major bleeding | Non-inferior composite endpoint of VTE/major bleeding |
Young et al. 2018 (SELECT-D) | Phase III (C) | Rivaroxaban | Seems to have inferior rate of VTE recurrence | Superior rates of clinically relevant non-major bleeding |
Anticoagulation
- Dalteparin (Fragmin) as follows:
- First month: 200 IU/kg once per day
- Subsequent months: 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
- 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 contains protocol PubMed
- 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 contains protocol PubMed
Edoxaban monotherapy
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Variant #1, reduced dose
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Büller et al. 2013 (Hokusai-VTE) | Phase III (E) | Warfarin | Non-inferior recurrent VTE rate | Superior rate of bleeding |
Raskob et al. 2017 (Hokusai VTE Cancer) | Phase III (E) | Dalteparin | Non-inferior composite endpoint of VTE/major bleeding | Non-inferior composite endpoint of VTE/major bleeding |
Note: this dose was used for patients with CrCl of 30 to 50 mL/min/1.73m2, a body weight of up to 60 kg, or those taking "potent" P-glycoprotein inhibitors.
Anticoagulation
- Therapeutic dose LMWH for at least 5 days, then:
- Edoxaban (Savaysa) 30 mg PO once per day
3- to 12-month course
Variant #2, normal dosing
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Büller et al. 2013 (Hokusai-VTE) | Phase III (E) | Warfarin | Non-inferior recurrent VTE rate | Lower rates of bleeding |
Raskob et al. 2017 (Hokusai VTE Cancer) | Phase III (E) | Dalteparin | Non-inferior composite endpoint of VTE/major bleeding | Non-inferior composite 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
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 contains verified protocol PubMed
- 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 contains protocol PubMed
Enoxaparin monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Kearon et al. 2006 (FIDO) | Phase III (E) | 1. Dalteparin 2. UFH |
No difference in recurrent VTE or major bleeding |
Anticoagulation
- Enoxaparin (Lovenox) SC 100 IU/kg 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 Aug23;296(8):935-42. link to original article PubMed
Fondaparinux monotherapy
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Regimen
Anticoagulation
References
To be completed
Heparin monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Loewe & Hirsch 1947 | Observational | None | 2.4% fatality rate due to pulmonary embolism |
Kearon et al. 2006 (FIDO) | Phase III (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) SC 333 units/kg once, then 250 units/kg 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 Aug23;296(8):935-42. link to original article PubMed
Lepirudin monotherapy
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Regimen
Anticoagulation
References
To be completed
Rivaroxaban monotherapy
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Variant #1, 10 mg/day
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Weitz et al. 2017 (EINSTEIN CHOICE) | Phase III (E) | 1. Aspirin | Superior symptomatic recurrent VTE rate | Similar major bleeding |
2. Rivaroxaban 20 mg | Seems not superior | Similar major bleeding |
Preceding treatment
- 6 to 12 months of a vitamin K antagonist or a direct oral anticoagulant
Anticoagulation
- Rivaroxaban (Xarelto) 10 mg PO once per day
Up to 12-month course
Variant #2, 20 mg/day
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Weitz et al. 2017 (EINSTEIN CHOICE) | Phase III (E) | 1. Aspirin | Superior symptomatic recurrent VTE rate | Similar major bleeding |
2. Rivaroxaban 10 mg | Seems not superior | Similar major bleeding |
Preceding treatment
- 6 to 12 months of a vitamin K antagonist or a direct oral anticoagulant
Anticoagulation
- Rivaroxaban (Xarelto) 20 mg PO once per day
Up to 12-month course
Variant #3, 20 mg/day with loading dose
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Bauersachs et al. 2010 (EINSTEIN Acute DVT) | Phase III (E) | Warfarin | Non-inferior VTE recurrence | Similar major bleeding |
Büller et al. 2012 (EINSTEIN-PE) | Phase III (E) | Warfarin | Non-inferior symptomatic VTE recurrence | Similar major bleeding |
Young et al. 2018 (SELECT-D) | Phase III (E) | Dalteparin | Seems to have superior rate of VTE recurrence | 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 contains verified protocol PubMed
- 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 contains protocol PubMed
- 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
- 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
- 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 contains protocol PubMed
Tinzaparin monotherapy
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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
Warfarin monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Schulman et al. 2009 (RE-COVER) | Phase III (C) | Dabigatran | Non-inferior composite endpoint | Similar major bleeding |
Bauersachs et al. 2010 (EINSTEIN Acute DVT) | Phase III (C) | Rivaroxaban | Non-inferior VTE recurrence | Similar major bleeding |
Büller et al. 2012 (EINSTEIN-PE) | Phase III (C) | Rivaroxaban | Non-inferior VTE recurrence | Similar major bleeding |
Agnelli et al. 2013 (AMPLIFY) | Phase III (C) | Apixaban | Non-inferior composite endpoint | Higher rates of bleeding |
Büller et al. 2013 (Hokusai-VTE) | Phase III (C) | Edoxaban | Non-inferior recurrent VTE rate | Higher rates of bleeding |
Anticoagulation
- Warfarin (Coumadin) with goal INR between 2.0 and 3.0
Supportive medications
- Most protocols: Enoxaparin (Lovenox) 1 mg/kg SC every 12 hours until INR greater than 2.0
3-, 6-, or 12- month course (see individual papers)
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
- 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 contains verified protocol PubMed
- 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 contains verified protocol PubMed
- 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 contains protocol PubMed
- 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
- 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 contains verified protocol PubMed
- 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 contains verified protocol PubMed
- 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
- 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
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