Difference between revisions of "Venous thromboembolism"
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====Preceding treatment==== | ====Preceding treatment==== | ||
*Total knee replacement | *Total knee replacement | ||
− | ==== | + | ====Anticoagulation==== |
*[[Apixaban (Eliquis)]] 2.5 mg PO BID, beginning 12 to 24 h after wound closure | *[[Apixaban (Eliquis)]] 2.5 mg PO BID, beginning 12 to 24 h after wound closure | ||
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====Preceding treatment==== | ====Preceding treatment==== | ||
*Total hip replacement | *Total hip replacement | ||
− | ==== | + | ====Anticoagulation==== |
*[[Apixaban (Eliquis)]] 2.5 mg PO BID, beginning 12 to 24 h after wound closure | *[[Apixaban (Eliquis)]] 2.5 mg PO BID, beginning 12 to 24 h after wound closure | ||
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|- | |- | ||
|} | |} | ||
− | ==== | + | ====Anticoagulation==== |
*[[Aspirin]] 81 to 160 mg PO once per day | *[[Aspirin]] 81 to 160 mg PO once per day | ||
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|- | |- | ||
|} | |} | ||
− | ==== | + | ====Anticoagulation==== |
*[[Betrixaban (Bevyxxa)]] 80 mg PO once per day | *[[Betrixaban (Bevyxxa)]] 80 mg PO once per day | ||
===References=== | ===References=== | ||
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====Preceding treatment==== | ====Preceding treatment==== | ||
*Total knee replacement | *Total knee replacement | ||
− | ==== | + | ====Anticoagulation==== |
*[[Enoxaparin (Lovenox)]] 40 mg SC q12h, beginning 12 to 24 h after wound closure | *[[Enoxaparin (Lovenox)]] 40 mg SC q12h, beginning 12 to 24 h after wound closure | ||
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*ADVANCE-2: Total knee replacement | *ADVANCE-2: Total knee replacement | ||
*ADVANCE-3: Total hip replacement | *ADVANCE-3: Total hip replacement | ||
− | ==== | + | ====Anticoagulation==== |
*[[Enoxaparin (Lovenox)]] 40 mg SC once per day | *[[Enoxaparin (Lovenox)]] 40 mg SC once per day | ||
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|- | |- | ||
|} | |} | ||
− | ==== | + | ====Anticoagulation==== |
*[[Rivaroxaban (Xarelto)]] 10 mg PO once per day for 35 +/- 4 days | *[[Rivaroxaban (Xarelto)]] 10 mg PO once per day for 35 +/- 4 days | ||
===References=== | ===References=== | ||
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====Preceding treatment==== | ====Preceding treatment==== | ||
*Therapeutic anticoagulation x 6-12 mo | *Therapeutic anticoagulation x 6-12 mo | ||
− | ==== | + | ====Anticoagulation==== |
*[[Apixaban (Eliquis)]] 2.5 mg PO BID | *[[Apixaban (Eliquis)]] 2.5 mg PO BID | ||
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====Preceding treatment==== | ====Preceding treatment==== | ||
*Therapeutic anticoagulation x 6-12 mo | *Therapeutic anticoagulation x 6-12 mo | ||
− | ==== | + | ====Anticoagulation==== |
*[[Apixaban (Eliquis)]] 5 mg PO BID | *[[Apixaban (Eliquis)]] 5 mg PO BID | ||
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*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==== |
*[[Aspirin]] 100 mg PO once per day | *[[Aspirin]] 100 mg PO once per day | ||
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|- | |- | ||
|} | |} | ||
− | ==== | + | ====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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|- | |- | ||
|} | |} | ||
− | ==== | + | ====Anticoagulation==== |
*[[Enoxaparin (Lovenox)]] 1.5 mg/kg SC once per day | *[[Enoxaparin (Lovenox)]] 1.5 mg/kg SC once per day | ||
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|- | |- | ||
|} | |} | ||
− | ==== | + | ====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 | ||
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====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==== |
*[[Warfarin (Coumadin)]] PO titrated to goal INR 1.5 to 2.0 | *[[Warfarin (Coumadin)]] PO titrated to goal INR 1.5 to 2.0 | ||
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|- | |- | ||
|} | |} | ||
− | ==== | + | ====Anticoagulation==== |
*[[Apixaban (Eliquis)]] 10 mg PO BID for 7 days, then 5 mg PO BID | *[[Apixaban (Eliquis)]] 10 mg PO BID for 7 days, then 5 mg PO BID | ||
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|} | |} | ||
===Regimen {{#subobject:3f6d7f|Variant=1}}=== | ===Regimen {{#subobject:3f6d7f|Variant=1}}=== | ||
− | ==== | + | ====Anticoagulation==== |
*[[Argatroban (Acova)]] | *[[Argatroban (Acova)]] | ||
===References=== | ===References=== | ||
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*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==== |
*[[Aspirin]] 100 mg PO once per day | *[[Aspirin]] 100 mg PO once per day | ||
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|} | |} | ||
===Regimen {{#subobject:5faf02|Variant=1}}=== | ===Regimen {{#subobject:5faf02|Variant=1}}=== | ||
− | ==== | + | ====Anticoagulation==== |
*[[Bivalirudin (Angiomax)]] | *[[Bivalirudin (Angiomax)]] | ||
===References=== | ===References=== | ||
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|- | |- | ||
|} | |} | ||
− | ==== | + | ====Anticoagulation==== |
*[[Dabigatran (Pradaxa)]] 150 mg PO BID | *[[Dabigatran (Pradaxa)]] 150 mg PO BID | ||
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|- | |- | ||
|} | |} | ||
− | ==== | + | ====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 | ||
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|} | |} | ||
''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==== |
*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 | ||
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|- | |- | ||
|} | |} | ||
− | ==== | + | ====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 | ||
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|} | |} | ||
− | ==== | + | ====Anticoagulation==== |
*[[Enoxaparin (Lovenox)]] | *[[Enoxaparin (Lovenox)]] | ||
===References=== | ===References=== | ||
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|} | |} | ||
===Regimen {{#subobject:ab5c25|Variant=1}}=== | ===Regimen {{#subobject:ab5c25|Variant=1}}=== | ||
− | ==== | + | ====Anticoagulation==== |
*[[Fondaparinux (Arixtra)]] | *[[Fondaparinux (Arixtra)]] | ||
===References=== | ===References=== | ||
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!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | !style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://jamanetwork.com/journals/jama/fullarticle/203221 Kearon et al. 2006 (FIDO)] |
| style="background-color:#1a9851" |Phase III (C) | | style="background-color:#1a9851" |Phase III (C) | ||
|[[#Dalteparin_monotherapy_2|Dalteparin]]<br> [[#Enoxaparin_monotherapy_3|Enoxaparin]] | |[[#Dalteparin_monotherapy_2|Dalteparin]]<br> [[#Enoxaparin_monotherapy_3|Enoxaparin]] | ||
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|} | |} | ||
− | ==== | + | ====Anticoagulation==== |
*[[Heparin]] administered subcutaneously, initial dose 333 U/kg, followed by a fixed dose of 250 U/kg every 12 hours | *[[Heparin]] administered subcutaneously, initial dose 333 U/kg, followed by a fixed dose of 250 U/kg every 12 hours | ||
===References=== | ===References=== | ||
Line 848: | Line 848: | ||
|} | |} | ||
===Regimen {{#subobject:22918f|Variant=1}}=== | ===Regimen {{#subobject:22918f|Variant=1}}=== | ||
− | ==== | + | ====Anticoagulation==== |
*[[Lepirudin (Refludan)]] | *[[Lepirudin (Refludan)]] | ||
===References=== | ===References=== | ||
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====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==== |
*[[Rivaroxaban (Xarelto)]] 10 mg PO once per day | *[[Rivaroxaban (Xarelto)]] 10 mg PO once per day | ||
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====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==== |
*[[Rivaroxaban (Xarelto)]] 20 mg PO once per day | *[[Rivaroxaban (Xarelto)]] 20 mg PO once per day | ||
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|- | |- | ||
|} | |} | ||
− | ==== | + | ====Anticoagulation==== |
*[[Rivaroxaban (Xarelto)]] 15 mg PO BID for 3 weeks, then 20 mg PO once per day | *[[Rivaroxaban (Xarelto)]] 15 mg PO BID for 3 weeks, then 20 mg PO once per day | ||
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===Regimen {{#subobject:24b40c|Variant=1}}=== | ===Regimen {{#subobject:24b40c|Variant=1}}=== | ||
''Note: this agent has been withdrawn from the US market.'' | ''Note: this agent has been withdrawn from the US market.'' | ||
− | ==== | + | ====Anticoagulation==== |
*[[Tinzaparin (Innohep)]] | *[[Tinzaparin (Innohep)]] | ||
===References=== | ===References=== | ||
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|- | |- | ||
|} | |} | ||
− | ==== | + | ====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==== |
Revision as of 12:17, 13 September 2018
Section editors | |||
---|---|---|---|
Shruti Chaturvedi, MBBS, MSCI Baltimore, MD |
Benjamin Tillman, MD 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
Current
- 2015: ASCO Clinical Practice Guideline on VTE prophylaxis and treatment 2014 update
- 2013: Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update PubMed
Older
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
FDA-recommended dose |
Study | Evidence | Comparator | Efficacy | 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 BID, beginning 12 to 24 h after wound closure
10- to 14-day course
Variant #2, 35 days
FDA-recommended dose |
Study | Evidence | Comparator | Efficacy | 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 BID, beginning 12 to 24 h after wound closure
35-day 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
Aspirin monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Pulmonary Embolism Prevention (PEP) trial Collaborative Group 2000 | 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) | Enoxaparin 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: 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
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Cohen et al. 2016 (APEX) | Phase III (E) | Enoxaparin | Might have lower rates of VTE |
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 q12h
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Lassen et al. 2009 (ADVANCE-1)] | Phase III (C) | Apixaban | Seems not superior | Seems to have higher bleeding rate |
Preceding treatment
- Total knee replacement
Anticoagulation
- Enoxaparin (Lovenox) 40 mg SC q12h, beginning 12 to 24 h after wound closure
10- to 14-day course
Variant #2, 40 mg daily
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
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 |
Lassen et al. 2010 (ADVANCE-3) | Phase III (C) | Apixaban | Inferior composite outcome |
Palumbo et al. 2011 | Phase III (E) | Aspirin Low-dose warfarin |
Seems not superior |
Larocca et al. 2011 | Phase III (E) | Aspirin | Seems not superior |
Cohen et al. 2013 (MAGELLAN) | Phase III (C) | Rivaroxaban | Non-inferior VTE rate at 10 days |
Cohen et al. 2016 (APEX) | Phase III (C) | Betrixaban | Might have higher rates of VTE |
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
- 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
- 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
- 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
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 |
Anticoagulation
- Rivaroxaban (Xarelto) 10 mg PO once per day for 35 +/- 4 days
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
VTE secondary prevention
Apixaban monotherapy
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Variant #1, 2.5 mg BID
FDA-recommended dose |
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Agnelli et al. 2012 (AMPLIFY-EXT) | Phase III (E) | Apixaban 5 mg BID | Seems not superior |
Placebo | Superior composite endpoint |
Preceding treatment
- Therapeutic anticoagulation x 6-12 mo
Anticoagulation
- Apixaban (Eliquis) 2.5 mg PO BID
12-month course
Variant #2, 5 mg BID
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Agnelli et al. 2012 (AMPLIFY-EXT) | Phase III (E) | Apixaban 2.5 mg BID | Seems not superior |
Placebo | Superior composite endpoint |
Preceding treatment
- Therapeutic anticoagulation x 6-12 mo
Anticoagulation
- Apixaban (Eliquis) 5 mg PO BID
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
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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) | Phase III (E) | Placebo | Might have superior rate of VTE recurrence | No difference in bleeding rate |
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
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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
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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
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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 BID for 7 days, then 5 mg PO BID
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
back to top |
Regimen
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Weitz et al. 2017 (EINSTEIN CHOICE) | Phase III (C) | Rivaroxaban 10 mg | Inferior symptomatic recurrent VTE rate | Similar major bleeding |
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 BID
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
- Subset 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) | Dalteparin Heparin |
No difference in recurrent VTE or major bleeding |
Anticoagulation
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
back to top |
Regimen
Anticoagulation
References
To be completed
Heparin monotherapy
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Kearon et al. 2006 (FIDO) | Phase III (C) | Dalteparin Enoxaparin |
No difference in recurrent VTE or major bleeding |
Anticoagulation
- Heparin administered subcutaneously, initial dose 333 U/kg, followed by a fixed dose of 250 U/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
Lepirudin monotherapy
back to top |
Regimen
Anticoagulation
References
To be completed
Rivaroxaban monotherapy
back to top |
Variant #1, 10 mg/d
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Weitz et al. 2017 (EINSTEIN CHOICE) | Phase III (E) | Aspirin | Superior symptomatic recurrent VTE rate | Similar major bleeding |
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/d
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Weitz et al. 2017 (EINSTEIN CHOICE) | Phase III (E) | Aspirin | Superior symptomatic recurrent VTE rate | Similar major bleeding |
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/d 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 BID 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
back to top |
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
back to top |
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 q12h 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
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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