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Section editor transclusions 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

2012: Antithrombotic Therapy for VTE Disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

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
2007: Lyman et al. American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. PubMed

ASH

2021: Lyman et al. American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer
2020: Ortel et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism
2019: Anderson et al. American Society of Hematology 2019 guidelines for management of venous thromboembolism: prevention of venous thromboembolism in surgical hospitalized patients
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

"How I Treat"

2022: Schmidt & Lee. How I treat and prevent venous thrombotic complications in patients with lymphoma
2020: Klok & Huisman. How I assess and manage the risk of bleeding in patients treated for venous thromboembolism
2020: Middeldorp & Ganzevoort. How I treat venous thromboembolism in pregnancy
2020: Wang & Carrier. How I treat obese patients with oral anticoagulants
2019: Pabinger & Thaler. How I treat patients with hereditary antithrombin deficiency

IMWG

Current

IMWG guidelines for the prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma

Older

2007: Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma PubMed

ITAC (International Initiative on Thrombosis and Cancer)

2022: Farge et al. 2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19

Older

VTE primary prophylaxis

Apixaban monotherapy

Regimen variant #1, 10-14 days post-op

FDA-recommended dose

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Lassen et al. 2009 (ADVANCE-1)]	Phase 3 (E-switch-ic)	Enoxaparin	Inconclusive whether non-inferior asymptomatic and symptomatic DVT, nonfatal PE, and death from any cause during treatment	Seems to have lower bleeding rate
Lassen et al. 2010 (ADVANCE-2)	Phase 3 (E-switch-ic)	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

Regimen variant #2, 35 days post-op

FDA-recommended dose

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Lassen et al. 2010 (ADVANCE-3)	Phase 3 (E-switch-ic)	Enoxaparin	Superior composite endpoint	Did not meet endpoint of major and clinically relevant nonmajor bleeding

Preceding treatment

Total hip replacement

Anticoagulation

Apixaban (Eliquis) 2.5 mg PO twice per day, beginning 12 to 24 h after wound closure

35-day course

Regimen variant #3, 180 days

FDA-recommended dose

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Carrier et al. 2018 (AVERT)	Phase 3 (E-esc)	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 dosing details in abstract PubMed NCT00371683
ADVANCE-2: Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P; ADVANCE-2 investigators. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet. 2010 Mar 6;375(9717):807-15. link to original article contains dosing details in abstract PubMed NCT00452530
ADVANCE-3: Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM; ADVANCE-3 Investigators. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med. 2010 Dec 23;363(26):2487-98. link to original article PubMed NCT00423319
AVERT: Carrier M, Abou-Nassar K, Mallick R, Tagalakis V, Shivakumar S, Schattner A, Kuruvilla P, Hill D, Spadafora S, Marquis K, Trinkaus M, Tomiak A, Lee AYY, Gross PL, Lazo-Langner A, El-Maraghi R, Goss G, Le Gal G, Stewart D, Ramsay T, Rodger M, Witham D, Wells PS; AVERT Investigators. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med. 2019 Feb 21;380(8):711-719. Epub 2018 Dec 4. link to original article contains dosing details in manuscript PubMed NCT02048865

Aspirin monotherapy

Regimen

Study	Evidence	Comparator	Efficacy
Rodgers et al. 2000 (PEP)	Phase 3 (E-esc)	Placebo	Superior VTE rate
Landolfi et al. 2004 (ECLAP)	Phase 3 (E-esc)	Placebo	Seems to have superior rate of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes
Palumbo et al. 2011 (GIMEMA MM-03-05)	Phase 3 (E-switch-ic)	1. Enoxaparin 2. Warfarin; low-dose	Did not meet primary endpoint of serious thromboembolic events, acute cardiovascular events, or sudden deaths during the first 6 months of treatment
Larocca et al. 2011 (MPRvsMEL200)	Phase 3 (E-de-esc)	Enoxaparin	Did not meet primary endpoint of VTE incidence
Anderson et al. 2013 (EPCAT)	Phase 3 (E-de-esc)	Dalteparin	Non-inferior VTE rate at 90 days
Anderson et al. 2018 (EPCAT II)	Phase 3 (E-de-esc)	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
GIMEMA MM-03-05: Palumbo A, Cavo M, Bringhen S, Zamagni E, Romano A, Patriarca F, Rossi D, Gentilini F, Crippa C, Galli M, Nozzoli C, Ria R, Marasca R, Montefusco V, Baldini L, Elice F, Callea V, Pulini S, Carella AM, Zambello R, Benevolo G, Magarotto V, Tacchetti P, Pescosta N, Cellini C, Polloni C, Evangelista A, Caravita T, Morabito F, Offidani M, Tosi P, Boccadoro M. Aspirin, warfarin, or enoxaparin thromboprophylaxis in patients with multiple myeloma treated with thalidomide: a phase III, open-label, randomized trial. J Clin Oncol. 2011 Mar 10;29(8):986-93. Epub 2011 Jan 31. link to original article PubMed NCT01063179
MPRvsMEL200: Larocca A, Cavallo F, Bringhen S, Di Raimondo F, Falanga A, Evangelista A, Cavalli M, Stanevsky A, Corradini P, Pezzatti S, Patriarca F, Cavo M, Peccatori J, Catalano L, Carella AM, Cafro AM, Siniscalchi A, Crippa C, Petrucci MT, Yehuda DB, Beggiato E, Di Toritto TC, Boccadoro M, Nagler A, Palumbo A. Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide. Blood. 2012 Jan 26;119(4):933-9. Epub 2011 Aug 11. link to original article PubMed NCT00551928
EPCAT: Anderson DR, Dunbar MJ, Bohm ER, Belzile E, Kahn SR, Zukor D, Fisher W, Gofton W, Gross P, Pelet S, Crowther M, MacDonald S, Kim P, Pleasance S, Davis N, Andreou P, Wells P, Kovacs M, Rodger MA, Ramsay T, Carrier M, Vendittoli PA. Aspirin versus low-molecular-weight heparin for extended venous thromboembolism prophylaxis after total hip arthroplasty: a randomized trial. Ann Intern Med. 2013 Jun 4;158(11):800-6. link to original article PubMed ISRCTN11902170
EPCAT II: Anderson DR, Dunbar M, Murnaghan J, Kahn SR, Gross P, Forsythe M, Pelet S, Fisher W, Belzile E, Dolan S, Crowther M, Bohm E, MacDonald SJ, Gofton W, Kim P, Zukor D, Pleasance S, Andreou P, Doucette S, Theriault C, Abianui A, Carrier M, Kovacs MJ, Rodger MA, Coyle D, Wells PS, Vendittoli PA. Aspirin or rivaroxaban for VTE prophylaxis after hip or knee arthroplasty. N Engl J Med. 2018 Feb 22;378(8):699-707. link to original article PubMed NCT01720108

Betrixaban monotherapy

Regimen

Study	Evidence	Comparator	Efficacy
Cohen et al. 2016 (APEX-VTE)	Phase 3 (E-switch-ic)	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 NCT01583218

Enoxaparin monotherapy

Regimen variant #1, 30 mg every 12 hours

Study	Evidence	Comparator	Efficacy	Toxicity
Geerts et al. 1996	Phase 3 (E-switch-ic)	UFH	Superior DVT rates	No difference in major bleeding rate
Lassen et al. 2009 (ADVANCE-1)]	Phase 3 (C)	Apixaban	Inconclusive whether non-inferior asymptomatic and symptomatic DVT, nonfatal PE, and death from any cause during treatment	Seems to have higher bleeding rate

Preceding treatment

ADVANCE-1: Total knee replacement
The study population in Geerts et. al. were trauma patients without intracranial hemorrhage. Prophylaxis was initiated within 36 hours of the injury.

Anticoagulation

Enoxaparin (Lovenox) 30 mg SC every 12 hours, beginning 12 to 24 h after wound closure (ADVANCE-1), 10- to 14-day course
The comparison arm in Geerts et al. used heparin 5000 units subcutaneous every 12 hours.

Regimen variant #2, 40 mg daily

Study	Evidence	Comparator	Efficacy
Samama et al. 1999 (MEDENOX)	Phase 3 (C)	1. Placebo 2. Enoxaparin; 20 mg daily	Superior VTE rates
Kakkar et al. 2008 (RECORD2)	Phase 3 (C)	Rivaroxaban	Inferior composite outcome
Erikkson et al. 2008 (RECORD1)	Phase 3 (C)	Rivaroxaban	Inferior composite outcome
Lassen et al. 2008 (RECORD3)	Phase 3 (C)	Rivaroxaban	Inferior composite outcome
Turpie et al. 2009 (RECORD4)	Phase 3 (C)	Rivaroxaban	Seems to have inferior composite outcome
Lassen et al. 2010 (ADVANCE-2)	Phase 3 (C)	Apixaban	Inferior composite outcome
Hull et al. 2010 (EXCLAIM)	Phase 3 (E-esc)	Placebo	Superior composite VTE rate
Lassen et al. 2010 (ADVANCE-3)	Phase 3 (C)	Apixaban	Inferior composite outcome
Palumbo et al. 2011 (GIMEMA MM-03-05)	Phase 3 (E-switch-ic)	1. Aspirin 2. Warfarin; low-dose	Did not meet primary endpoint of serious thromboembolic events, acute cardiovascular events, or sudden deaths during the first 6 months of treatment
Larocca et al. 2011 (MPRvsMEL200)	Phase 3 (E-esc)	Aspirin	Did not meet primary endpoint of VTE incidence
Goldhaber et al. 2011 (ADOPT)	Phase 3 (C)	Apixaban	Did not meet primary endpoint of 30-day composite of death related to venous thromboembolism, pulmonary embolism, symptomatic deep-vein thrombosis, or asymptomatic proximal-leg deep-vein thrombosis
Kakkar et al. 2011 (LIFENOX)	Phase 3 (E-esc)	Placebo	Did not meet primary endpoint of death rate at 30 days
Cohen et al. 2013 (MAGELLAN)	Phase 3 (C)	Rivaroxaban	Non-inferior VTE rate at 10 days
Cohen et al. 2016 (APEX-VTE)	Phase 3 (C)	Betrixaban	Might have higher rates of VTE
Sidhu et al. 2022 (CRISTAL)	Phase 3 (C)	Aspirin	Superior rate of symptomatic VTE within 90 days

Note: the APEX trial here should not be confused with the one in multiple myeloma.

Preceding treatment

ADVANCE-2 & CRISTAL: Total knee replacement
ADVANCE-3 & CRISTAL: Total hip replacement

Anticoagulation

Enoxaparin (Lovenox) 40 mg SC once per day

Various durations (see papers for details)

References

Geerts WH, Jay RM, Code KI, Chen E, Szalai JP, Saibil EA, Hamilton PA. A comparison of low-dose heparin with low-molecular-weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med. 1996 Sep 5;335(10):701-7. link to original article PubMed
MEDENOX: Samama MM, Cohen AT, Darmon JY, Desjardins L, Eldor A, Janbon C, Leizorovicz A, Nguyen H, Olsson CG, Turpie AG, Weisslinger N; MEDENOX Investigators. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. N Engl J Med. 1999; 341:793-800. link to original article. PubMed.
RECORD2: Kakkar AK, Brenner B, Dahl OE, Eriksson BI, Mouret P, Muntz J, Soglian AG, Pap AF, Misselwitz F, Haas S; RECORD2 Investigators. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet. 2008 Jul 5;372(9632):31-9. Epub 2008 Jun 24. link to original article PubMed NCT00332020
RECORD1: Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, Bandel TJ, Beckmann H, Muehlhofer E, Misselwitz F, Geerts W; RECORD1 Study Group. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008 Jun 26;358(26):2765-75. link to original article PubMed NCT00329628
RECORD3: Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, Misselwitz F, Turpie AG; RECORD3 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008 Jun 26;358(26):2776-86. link to original article PubMed NCT00361894
RECORD4: Turpie AG, Lassen MR, Davidson BL, Bauer KA, Gent M, Kwong LM, Cushner FD, Lotke PA, Berkowitz SD, Bandel TJ, Benson A, Misselwitz F, Fisher WD; RECORD4 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. 2009 May 16;373(9676):1673-80. Epub 2009 May 4. link to original article PubMed NCT00362232
ADVANCE-1: Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Portman RJ. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med. 2009 Aug 6;361(6):594-604. Erratum in: N Engl J Med. 2009 Oct 29;361(18):1814. link to original article contains dosing details in abstract PubMed NCT00371683
ADVANCE-2: Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P; ADVANCE-2 investigators. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet. 2010 Mar 6;375(9717):807-15. link to original article contains dosing details in abstract PubMed NCT00452530
EXCLAIM: Hull RD, Schellong SM, Tapson VF, Monreal M, Samama MM, Nicol P, Vicaut E, Turpie AG, Yusen RD; EXCLAIM (Extended Prophylaxis for Venous ThromboEmbolism in Acutely Ill Medical Patients With Prolonged Immobilization) study. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial. Ann Intern Med. 2010 Jul 6;153(1):8-18. link to original article PubMed NCT00077753
ADVANCE-3: Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM; ADVANCE-3 Investigators. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med. 2010 Dec 23;363(26):2487-98. link to original article contains dosing details in abstract PubMed NCT00423319
GIMEMA MM-03-05: Palumbo A, Cavo M, Bringhen S, Zamagni E, Romano A, Patriarca F, Rossi D, Gentilini F, Crippa C, Galli M, Nozzoli C, Ria R, Marasca R, Montefusco V, Baldini L, Elice F, Callea V, Pulini S, Carella AM, Zambello R, Benevolo G, Magarotto V, Tacchetti P, Pescosta N, Cellini C, Polloni C, Evangelista A, Caravita T, Morabito F, Offidani M, Tosi P, Boccadoro M. Aspirin, warfarin, or enoxaparin thromboprophylaxis in patients with multiple myeloma treated with thalidomide: a phase III, open-label, randomized trial. J Clin Oncol. 2011 Mar 10;29(8):986-93. Epub 2011 Jan 31. link to original article PubMed NCT01063179
MPRvsMEL200: Larocca A, Cavallo F, Bringhen S, Di Raimondo F, Falanga A, Evangelista A, Cavalli M, Stanevsky A, Corradini P, Pezzatti S, Patriarca F, Cavo M, Peccatori J, Catalano L, Carella AM, Cafro AM, Siniscalchi A, Crippa C, Petrucci MT, Yehuda DB, Beggiato E, Di Toritto TC, Boccadoro M, Nagler A, Palumbo A. Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide. Blood. 2012 Jan 26;119(4):933-9. Epub 2011 Aug 11. link to original article PubMed NCT00551928
ADOPT: Goldhaber SZ, Leizorovicz A, Kakkar AK, Haas SK, Merli G, Knabb RM, Weitz JI; ADOPT Trial Investigators. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med. 2011 Dec 8;365(23):2167-77. Epub 2011 Nov 13. link to original article PubMed NCT00457002
LIFENOX: Kakkar AK, Cimminiello C, Goldhaber SZ, Parakh R, Wang C, Bergmann JF; LIFENOX Investigators. Low-molecular-weight heparin and mortality in acutely ill medical patients. N Engl J Med. 2011 Dec 29;365(26):2463-72. link to original article PubMed NCT00622648
MAGELLAN: Cohen AT, Spiro TE, Büller HR, Haskell L, Hu D, Hull R, Mebazaa A, Merli G, Schellong S, Spyropoulos AC, Tapson V; MAGELLAN Investigators. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med. 2013 Feb 7;368(6):513-23. link to original article PubMed NCT00571649
APEX: 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 NCT01583218
CRISTAL: Sidhu VS, Kelly TL, Pratt N, Graves SE, Buchbinder R, Adie S, Cashman K, Ackerman I, Bastiras D, Brighton R, Burns AWR, Chong BH, Clavisi O, Cripps M, Dekkers M, de Steiger R, Dixon M, Ellis A, Griffith EC, Hale D, Hansen A, Harris A, Hau R, Horsley M, James D, Khorshid O, Kuo L, Lewis P, Lieu D, Lorimer M, MacDessi S, McCombe P, McDougall C, Mulford J, Naylor JM, Page RS, Radovanovic J, Solomon M, Sorial R, Summersell P, Tran P, Walter WL, Webb S, Wilson C, Wysocki D, Harris IA; CRISTAL Study Group. Effect of Aspirin vs Enoxaparin on Symptomatic Venous Thromboembolism in Patients Undergoing Hip or Knee Arthroplasty: The CRISTAL Randomized Trial. JAMA. 2022 Aug 23;328(8):719-727. link to original article PubMed ACTRN12618001879257

Placebo

Regimen

Study	Evidence	Comparator	Efficacy
Gärdlund et al. 1996	Phase 3 (C)	UFH; SC	Did not meet primary endpoint of necropsy-verified pulmonary embolism of predefined clinical relevance
Hull et al. 2010 (EXCLAIM)	Phase 3 (C)	Enoxaparin	Inferior composite VTE rate
Kakkar et al. 2011 (LIFENOX)	Phase 3 (C)	Enoxaparin	Did not meet primary endpoint of death rate at 30 days
Spyropoulos et al. 2018 (MARINER)	Phase 3 (C)	Rivaroxaban	Did not meet primary endpoint of symptomatic VTE or death due to VTE
Khorana et al. 2019 (CASSINI)	Phase 3 (C)	Rivaroxaban	Did not meet primary endpoint of objectively confirmed proximal DVT in a lower limb, PE, symptomatic DVT in an upper limb or distal DVT in a lower limb, and death from VTE up to 180 days

No active treatment.

References

Gärdlund B; 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 original 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 NCT00077753
LIFENOX: Kakkar AK, Cimminiello C, Goldhaber SZ, Parakh R, Wang C, Bergmann JF; LIFENOX Investigators. Low-molecular-weight heparin and mortality in acutely ill medical patients. N Engl J Med. 2011 Dec 29;365(26):2463-72. link to original article PubMed NCT00622648
MARINER: Spyropoulos AC, Ageno W, Albers GW, Elliott CG, Halperin JL, Hiatt WR, Maynard GA, Steg PG, Weitz JI, Suh E, Spiro TE, Barnathan ES, Raskob GE; MARINER Investigators. Rivaroxaban for thromboprophylaxis after hospitalization for medical illness. N Engl J Med. 2018 Sep 20;379(12):1118-1127. Epub 2018 Aug 26. link to original article PubMed NCT02111564
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 NCT02555878

Rivaroxaban monotherapy

Regimen

Study	Evidence	Comparator	Efficacy
Kakkar et al. 2008 (RECORD2)	Phase 3 (E-switch-ic)	Enoxaparin	Superior composite outcome
Erikkson et al. 2008 (RECORD1)	Phase 3 (E-switch-ic)	Enoxaparin	Superior composite outcome
Lassen et al. 2008 (RECORD3)	Phase 3 (E-switch-ic)	Enoxaparin	Superior composite outcome
Turpie et al. 2009 (RECORD4)	Phase 3 (E-switch-ic)	Enoxaparin	Seems to have superior composite outcome
Cohen et al. 2013 (MAGELLAN)	Phase 3 (E-switch-ic)	Enoxaparin	Non-inferior VTE rate at 10 days
Anderson et al. 2018 (EPCAT II)	Phase 3 (E-esc)	Aspirin	Non-inferior VTE rate at 90 days
Spyropoulos et al. 2018 (MARINER)	Phase 3 (E-esc)	Placebo	Did not meet primary endpoint of symptomatic VTE or death due to VTE

Anticoagulation

Rivaroxaban (Xarelto) 10 mg PO once per day for varying durations (see individual studies)

References

RECORD2: Kakkar AK, Brenner B, Dahl OE, Eriksson BI, Mouret P, Muntz J, Soglian AG, Pap AF, Misselwitz F, Haas S; RECORD2 Investigators. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet. 2008 Jul 5;372(9632):31-9. Epub 2008 Jun 24. link to original article PubMed NCT00332020
RECORD1: Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, Bandel TJ, Beckmann H, Muehlhofer E, Misselwitz F, Geerts W; RECORD1 Study Group. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008 Jun 26;358(26):2765-75. link to original article PubMed NCT00329628
RECORD3: Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, Misselwitz F, Turpie AG; RECORD3 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008 Jun 26;358(26):2776-86. link to original article PubMed NCT00361894
RECORD4: Turpie AG, Lassen MR, Davidson BL, Bauer KA, Gent M, Kwong LM, Cushner FD, Lotke PA, Berkowitz SD, Bandel TJ, Benson A, Misselwitz F, Fisher WD; RECORD4 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. 2009 May 16;373(9676):1673-80. Epub 2009 May 4. link to original article PubMed NCT00362232
MAGELLAN: Cohen AT, Spiro TE, Büller HR, Haskell L, Hu D, Hull R, Mebazaa A, Merli G, Schellong S, Spyropoulos AC, Tapson V; MAGELLAN Investigators. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med. 2013 Feb 7;368(6):513-23. link to original article PubMed NCT00571649
EPCAT II: Anderson DR, Dunbar M, Murnaghan J, Kahn SR, Gross P, Forsythe M, Pelet S, Fisher W, Belzile E, Dolan S, Crowther M, Bohm E, MacDonald SJ, Gofton W, Kim P, Zukor D, Pleasance S, Andreou P, Doucette S, Theriault C, Abianui A, Carrier M, Kovacs MJ, Rodger MA, Coyle D, Wells PS, Vendittoli PA. Aspirin or rivaroxaban for VTE prophylaxis after hip or knee arthroplasty. N Engl J Med. 2018 Feb 22;378(8):699-707. link to original article PubMed NCT01720108
MARINER: Spyropoulos AC, Ageno W, Albers GW, Elliott CG, Halperin JL, Hiatt WR, Maynard GA, Steg PG, Weitz JI, Suh E, Spiro TE, Barnathan ES, Raskob GE; MARINER Investigators. Rivaroxaban for thromboprophylaxis after hospitalization for medical illness. N Engl J Med. 2018 Sep 20;379(12):1118-1127. Epub 2018 Aug 26. link to original article PubMed NCT02111564

VTE secondary prevention

Apixaban monotherapy

Regimen variant #1, 2.5 mg twice per day

FDA-recommended dose

Study	Evidence	Comparator	Comparative Efficacy
Agnelli et al. 2012 (AMPLIFY-EXT)	Phase 3 (E-esc)	1. Apixaban; 5 mg twice per day	Did not meet primary endpoint of symptomatic recurrent VTE or death from any cause
Agnelli et al. 2012 (AMPLIFY-EXT)	Phase 3 (E-esc)	2. Placebo	Superior symptomatic recurrent VTE or death from any cause

Preceding treatment

Therapeutic anticoagulation x 6-12 mo

Anticoagulation

Apixaban (Eliquis) 2.5 mg PO twice per day

12-month course

Regimen variant #2, 5 mg twice per day

Study	Evidence	Comparator	Comparative Efficacy
Agnelli et al. 2012 (AMPLIFY-EXT)	Phase 3 (E-esc)	1. Apixaban; 2.5 mg twice per day	Did not meet primary endpoint of symptomatic recurrent VTE or death from any cause
Agnelli et al. 2012 (AMPLIFY-EXT)	Phase 3 (E-esc)	2. Placebo	Superior symptomatic recurrent VTE or death from any cause

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 dosing details in manuscript PubMed

Aspirin monotherapy

Regimen

Study	Evidence	Comparator	Efficacy	Toxicity
Becattini et al. 2012 (WARFASA)	Phase 3 (E-esc)	Placebo	Superior rate of VTE recurrence	No difference in bleeding rate
Brighton et al. 2012 (ASPIRE-VTE)	Phase 3 (E-esc)	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

WARFASA: Warfarin x 6 to 18 months
ASPIRE: Warfarin x 6 weeks to 24 months

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 dosing details in abstract PubMed NCT00222677
ASPIRE-VTE: Brighton TA, Eikelboom JW, Mann K, Mister R, Gallus A, Ockelford P, Gibbs H, Hague W, Xavier D, Diaz R, Kirby A, Simes J; ASPIRE Investigators. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med. 2012 Nov 22;367(21):1979-87. Epub 2012 Nov 4. link to original article PubMed ACTRN12605000004662

Dalteparin monotherapy

Regimen

Study	Evidence	Comparator	Efficacy	Toxicity
Lee et al. 2003 (CLOT)	Phase 3 (E-switch-ic)	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
1. 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

Regimen

Study	Evidence	Comparator	Efficacy
Meyer et al. 2002	Phase 3 (E-switch-ic)	Warfarin	Might have superior combined VTE/bleeding outcome

Anticoagulation

Enoxaparin (Lovenox) 1.5 mg/kg SC once per day

3-month course

References

Decousus H, Leizorovicz A, Parent F, Page Y, Tardy B, Girard P, Laporte S, Faivre R, Charbonnier B, Barral FG, Huet Y, Simonneau G; Prévention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group. A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. N Engl J Med. 1998 Feb 12;338(7):409-15. link to original article PubMed
Meyer G, Marjanovic Z, Valcke J, Lorcerie B, Gruel Y, Solal-Celigny P, Le Maignan C, Extra JM, Cottu P, Farge D. Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. Arch Intern Med. 2002 Aug 12-26;162(15):1729-35. link to original article contains dosing details in abstract PubMed

Warfarin monotherapy

Regimen variant #1, standard intensity

Study	Evidence	Comparator	Efficacy	Toxicity
Meyer et al. 2002	Phase 3 (C)	Enoxaparin	Might have inferior combined VTE/bleeding outcome
Lee et al. 2003 (CLOT)	Phase 3 (C)	Dalteparin	Inferior rate of VTE at 6 months	No difference in bleeding rate

Anticoagulation

Warfarin (Coumadin) PO titrated to goal INR 2 to 3.0

Regimen variant #2, low intensity

Study	Evidence	Comparator	Efficacy	Toxicity
Ridker et al. 2003 (PREVENT)	Phase 3 (E-esc)	Placebo	Superior recurrent VTE rate	No difference in major bleeding

Preceding treatment

Warfarin with goal INR of 2 to 3 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
Kearon C, Ginsberg JS, Kovacs MJ, Anderson DR, Wells P, Julian JA, MacKinnon B, Weitz JI, Crowther MA, Dolan S, Turpie AG, Geerts W, Solymoss S, van Nguyen P, Demers C, Kahn SR, Kassis J, Rodger M, Hambleton J, Gent M; Extended Low-Intensity Anticoagulation for Thrombo-Embolism Investigators. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med. 2003 Aug 14;349(7):631-9. link to original article PubMed
PREVENT: Ridker PM, Goldhaber SZ, Danielson E, Rosenberg Y, Eby CS, Deitcher SR, Cushman M, Moll S, Kessler CM, Elliott CG, Paulson R, Wong T, Bauer KA, Schwartz BA, Miletich JP, Bounameaux H, Glynn RJ; PREVENT Investigators. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med. 2003 Apr 10;348(15):1425-34. Epub 2003 Feb 24. link to original article contains dosing details in manuscript 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
1. 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

Regimen

FDA-recommended dose

Study	Evidence	Comparator	Efficacy	Toxicity
Agnelli et al. 2013 (AMPLIFY)	Phase 3 (E-switch-ic)	Warfarin	Non-inferior composite endpoint	Lower rates of bleeding
Angelli et al. 2020 (CARAVAGGIO)	Phase 3 (E-switch-ic)	Dalteparin	Non-inferior recurrent VTE	Major bleeding similar in both groups

Anticoagulation

Apixaban (Eliquis) 10 mg PO twice per day for 7 days, then 5 mg PO twice per day

6-month course

References

AMPLIFY: Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013 Aug 29;369(9):799-808. Epub 2013 Jul 1. link to original article contains dosing details in manuscript PubMed NCT00643201
CARAVAGGIO: Agnelli G, Becattini C, Meyer G, Munoz A, Huisman M, Connors J, Cohen A, Bauersachs R, Brenner B, Torbicki A, Sueiro M, Lambert C, Gussoni G, Campanini M, Fontanella A, Vescovo G, Verso M, Caravaggio Investigators. Apixaban for the treatment of venous thromboembolism associated with cancer. N Engl J Med. 2020 Apr 23;382(17):1599-1607. Epub 2020 Mar 29. link to original article PubMed NCT03045406

Argatroban monotherapy

Regimen

Anticoagulation

Argatroban (Acova)

References

To be completed

Aspirin monotherapy

Regimen

Study	Evidence	Comparator	Efficacy	Toxicity
Weitz et al. 2017 (EINSTEIN CHOICE)	Phase 3 (C)	1. Rivaroxaban; 10 mg/day	Inferior symptomatic recurrent VTE rate	Similar major bleeding
Weitz et al. 2017 (EINSTEIN CHOICE)	Phase 3 (C)	2. Rivaroxaban; 20 mg/day	Inferior symptomatic recurrent VTE rate	Similar major bleeding

Preceding treatment

6 to 12 months of a vitamin K antagonist or a direct oral anticoagulant

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 dosing details in manuscript PubMed NCT02064439

Bivalirudin monotherapy

Regimen

Anticoagulation

Bivalirudin (Angiomax)

References

To be completed

Dabigatran monotherapy

Regimen

Study	Evidence	Comparator	Efficacy	Toxicity
Schulman et al. 2009 (RE-COVER)	Phase 3 (E-switch-ic)	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 dosing details in manuscript PubMed NCT00291330
RE-MEDY: Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, Kvamme AM, Friedman J, Mismetti P, Goldhaber SZ; RE-MEDY Trial Investigators; RE-SONATE Trial Investigators. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):709-18. link to original article PubMed NCT00329238
RE-COVER II: Schulman S, Kakkar AK, Goldhaber SZ, Schellong S, Eriksson H, Mismetti P, Christiansen AV, Friedman J, Le Maulf F, Peter N, Kearon C; RE-COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014 Feb 18;129(7):764-72. Epub 2013 Dec 16. link to original article PubMed NCT00680186
DIVERSITY: Halton J, Brandão LR, Luciani M, Bomgaars L, Chalmers E, Mitchell LG, Nurmeev I, Sharathkumar A, Svirin P, Gorbatikov K, Tartakovsky I, Simetzberger M, Huang F, Sun Z, Kreuzer J, Gropper S, Reilly P, Brueckmann M, Albisetti M; DIVERSITY Trial Investigators. Dabigatran etexilate for the treatment of acute venous thromboembolism in children (DIVERSITY): a randomised, controlled, open-label, phase 2b/3, non-inferiority trial. Lancet Haematol. 2021 Jan;8(1):e22-e33. Epub 2020 Dec 5. link to original article PubMed NCT01895777

Dalteparin monotherapy

Regimen

Study	Evidence	Comparator	Efficacy	Toxicity
Francis et al. 2015 (DALTECAN)	Non-randomized
Raskob et al. 2017 (Hokusai VTE Cancer)	Phase 3 (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 3 (C)	Rivaroxaban	Seems to have inferior rate of VTE recurrence	Superior rates of clinically relevant non-major bleeding
Angelli et al. 2020 (CARAVAGGIO)	Phase 3 (C)	Apixaban	Non-inferior recurrent VTE	Major bleeding similar in both groups

Anticoagulation

Dalteparin (Fragmin) as follows:
- First month: 200 IU/kg once per day
- Month 2 onwards: 150 IU/kg once per day

6- to 12-month course

References

DALTECAN: Francis CW, Kessler CM, Goldhaber SZ, Kovacs MJ, Monreal M, Huisman MV, Bergqvist D, Turpie AG, Ortel TL, Spyropoulos AC, Pabinger I, Kakkar AK. Treatment of venous thromboembolism in cancer patients with dalteparin for up to 12 months: the DALTECAN Study. J Thromb Haemost. 2015 Jun;13(6):1028-35. Epub 2015 May 10. link to original article PubMed NCT00942968
Hokusai VTE Cancer: Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia D, Grosso MA, Kakkar AK, Kovacs MJ, Mercuri MF, Meyer G, Segers A, Shi M, Wang TF, Yeo E, Zhang G, Zwicker JI, Weitz JI, Büller HR; Hokusai VTE Cancer Investigators. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med. 2018 Feb 15;378(7):615-624. Epub 2017 Dec 12. link to original article contains dosing details in abstract PubMed NCT02073682
SELECT-D: Young AM, Marshall A, Thirlwall J, Chapman O, Lokare A, Hill C, Hale D, Dunn JA, Lyman GH, Hutchinson C, MacCallum P, Kakkar A, Hobbs FDR, Petrou S, Dale J, Poole CJ, Maraveyas A, Levine M. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol. 2018 Jul 10;36(20):2017-2023. Epub 2018 May 10. link to original article contains dosing details in abstract PubMed ISRCTN86712308
CARAVAGGIO: Agnelli G, Becattini C, Meyer G, Munoz A, Huisman M, Connors J, Cohen A, Bauersachs R, Brenner B, Torbicki A, Sueiro M, Lambert C, Gussoni G, Campanini M, Fontanella A, Vescovo G, Verso M, Caravaggio Investigators. Apixaban for the treatment of venous thromboembolism associated with cancer. N Engl J Med. 2020 Apr 23;382(17):1599-1607. Epub 2020 Mar 29. link to original article PubMed NCT03045406

Edoxaban monotherapy

Regimen variant #1, reduced dose

Study	Evidence	Comparator	Efficacy	Toxicity
Büller et al. 2013 (Hokusai-VTE)	Phase 3 (E-switch-ic)	Warfarin	Non-inferior recurrent VTE rate	Superior rate of bleeding
Raskob et al. 2017 (Hokusai VTE Cancer)	Phase 3 (E-switch-ic)	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

Regimen variant #2, normal dosing

Study	Evidence	Comparator	Efficacy	Toxicity
Büller et al. 2013 (Hokusai-VTE)	Phase 3 (E-switch-ic)	Warfarin	Non-inferior recurrent VTE rate	Lower rates of bleeding
Raskob et al. 2017 (Hokusai VTE Cancer)	Phase 3 (E-switch-ic)	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 dosing details in manuscript PubMed NCT00986154
1. 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 dosing details in abstract PubMed NCT02073682

Enoxaparin monotherapy

Regimen

Study	Evidence	Comparator	Efficacy
Kearon et al. 2006 (FIDO)	Phase 3 (E-switch-ic)	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 Aug 23;296(8):935-42. link to original article PubMed NCT00182403

Fondaparinux monotherapy

Regimen

Anticoagulation

Fondaparinux (Arixtra)

References

To be completed

Heparin monotherapy

UFH: UnFractionated Heparin

Regimen

Study	Evidence	Comparator	Efficacy
Loewe & Hirsch 1947	Observational	None	2.4% fatality rate due to pulmonary embolism
Kearon et al. 2006 (FIDO)	Phase 3 (C)	1. Dalteparin 2. Enoxaparin	No difference in recurrent VTE or major bleeding

Note: In Loewe and Hirsch, heparin was administered as a deep subcutaneous injection (200 to 400 mg / 200,000 to 400,000 IU) in Pitkin menstruum every two to three days for 10 to 14 days for deep vein thrombosis and extended for one to two additional weeks for pulmonary embolism.

Anticoagulation

Unfractionated heparin (UFH) 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 Aug 23;296(8):935-42. link to original article PubMed NCT00182403

Lepirudin monotherapy

Regimen

Anticoagulation

Lepirudin (Refludan)

References

To be completed

Rivaroxaban monotherapy

Regimen variant #1, 10 mg/day

Study	Evidence	Comparator	Efficacy	Toxicity
Weitz et al. 2017 (EINSTEIN CHOICE)	Phase 3 (E-esc)	1. Aspirin	Superior symptomatic recurrent VTE rate	Similar major bleeding
Weitz et al. 2017 (EINSTEIN CHOICE)	Phase 3 (E-esc)	2. Rivaroxaban; 20 mg/day	Did not meet primary endpoint of symptomatic recurrent VTE rate	Similar major bleeding

Preceding treatment

6 to 12 months of a vitamin K antagonist or a direct oral anticoagulant

Anticoagulation

Rivaroxaban (Xarelto) 10 mg PO once per day

Up to 12-month course

Regimen variant #2, 20 mg/day

Study	Evidence	Comparator	Efficacy	Toxicity
Weitz et al. 2017 (EINSTEIN CHOICE)	Phase 3 (E-esc)	1. Aspirin	Superior symptomatic recurrent VTE rate	Similar major bleeding
Weitz et al. 2017 (EINSTEIN CHOICE)	Phase 3 (E-esc)	2. Rivaroxaban; 10 mg/day	Did not meet primary endpoint of symptomatic recurrent VTE rate	Similar major bleeding

Preceding treatment

6 to 12 months of a vitamin K antagonist or a direct oral anticoagulant

Anticoagulation

Rivaroxaban (Xarelto) 20 mg PO once per day

Up to 12-month course

Regimen variant #3, 20 mg/day with loading dose

Study	Evidence	Comparator	Efficacy	Toxicity
Bauersachs et al. 2010 (EINSTEIN Acute DVT)	Phase 3 (E-switch-ic)	Warfarin	Non-inferior VTE recurrence	Similar major bleeding
Büller et al. 2012 (EINSTEIN-PE)	Phase 3 (E-switch-ic)	Warfarin	Non-inferior symptomatic VTE recurrence	Similar major bleeding
Young et al. 2018 (SELECT-D)	Phase 3 (E-switch-ic)	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 dosing details in manuscript PubMed NCT00440193; NCT00439725
EINSTEIN-PE: Büller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A; EINSTEIN-PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012 Apr 5;366(14):1287-97. Epub 2012 Mar 26. link to original article contains dosing details in abstract PubMed NCT00439777
XALIA: Ageno W, Mantovani LG, Haas S, Kreutz R, Monje D, Schneider J, van Eickels M, Gebel M, Zell E, Turpie AG. Safety and effectiveness of oral rivaroxaban versus standard anticoagulation for the treatment of symptomatic deep-vein thrombosis (XALIA): an international, prospective, non-interventional study. Lancet Haematol. 2016 Jan;3(1):e12-21. Epub 2015 Dec 8. link to original article PubMed NCT01619007
EINSTEIN CHOICE: Weitz JI, Lensing AWA, Prins MH, Bauersachs R, Beyer-Westendorf J, Bounameaux H, Brighton TA, Cohen AT, Davidson BL, Decousus H, Freitas MCS, Holberg G, Kakkar AK, Haskell L, van Bellen B, Pap AF, Berkowitz SD, Verhamme P, Wells PS, Prandoni P; EINSTEIN CHOICE Investigators. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med. 2017 Mar 30;376(13):1211-1222. Epub 2017 Mar 18. link to original article PubMed NCT02064439
SELECT-D: Young AM, Marshall A, Thirlwall J, Chapman O, Lokare A, Hill C, Hale D, Dunn JA, Lyman GH, Hutchinson C, MacCallum P, Kakkar A, Hobbs FDR, Petrou S, Dale J, Poole CJ, Maraveyas A, Levine M. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol. 2018 Jul 10;36(20):2017-2023. Epub 2018 May 10. link to original article contains dosing details in abstract PubMed ISRCTN86712308
EINSTEIN Junior: Male C, Lensing AWA, Palumbo JS, Kumar R, Nurmeev I, Hege K, Bonnet D, Connor P, Hooimeijer HL, Torres M, Chan AKC, Kenet G, Holzhauer S, Santamaría A, Amedro P, Chalmers E, Simioni P, Bhat RV, Yee DL, Lvova O, Beyer-Westendorf J, Biss TT, Martinelli I, Saracco P, Peters M, Kállay K, Gauger CA, Massicotte MP, Young G, Pap AF, Majumder M, Smith WT, Heubach JF, Berkowitz SD, Thelen K, Kubitza D, Crowther M, Prins MH, Monagle P; EINSTEIN-Jr Phase 3 Investigators. Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial. Lancet Haematol. 2020 Jan;7(1):e18-e27. Epub 2019 Nov 5. link to original article PubMed NCT02234843

Tinzaparin monotherapy

Regimen

Note: this agent has been withdrawn from the US market.

Anticoagulation

Tinzaparin (Innohep)

References

LITE: Hull RD, Pineo GF, Brant RF, Mah AF, Burke N, Dear R, Wong T, Cook R, Solymoss S, Poon MC, Raskob G; LITE Trial Investigators. Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer. Am J Med. 2006 Dec;119(12):1062-72. link to original article PubMed
CATCH: Lee AY, Kamphuisen PW, Meyer G, Bauersachs R, Janas MS, Jarner MF, Khorana AA; CATCH Investigators. Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: A randomized clinical trial. JAMA. 2015 Aug 18;314(7):677-86. link to original article PubMed NCT01130025

Warfarin monotherapy

Regimen

Study	Evidence	Comparator	Efficacy	Toxicity
Schulman et al. 2009 (RE-COVER)	Phase 3 (C)	Dabigatran	Non-inferior composite endpoint	Similar major bleeding
Bauersachs et al. 2010 (EINSTEIN Acute DVT)	Phase 3 (C)	Rivaroxaban	Non-inferior VTE recurrence	Similar major bleeding
Büller et al. 2012 (EINSTEIN-PE)	Phase 3 (C)	Rivaroxaban	Non-inferior VTE recurrence	Similar major bleeding
Agnelli et al. 2013 (AMPLIFY)	Phase 3 (C)	Apixaban	Non-inferior composite endpoint	Higher rates of bleeding
Büller et al. 2013 (Hokusai-VTE)	Phase 3 (C)	Edoxaban	Non-inferior recurrent VTE rate	Higher rates of bleeding
Lee et al. 2015 (CATCH)	Phase 3 (C)	Tinzaparin	Might have inferior composite outcome	Similar major bleeding

Anticoagulation

Warfarin (Coumadin) with goal INR between 2 and 3.0

Supportive therapy

Most protocols: Enoxaparin (Lovenox) 1 mg/kg SC every 12 hours until INR greater than 2.0

3-, 6-, or 12- month course (see individual papers)

References

Schulman S, Rhedin AS, Lindmarker P, Carlsson A, Lärfars G, Nicol P, Loogna E, Svensson E, Ljungberg B, Walter H; Duration of Anticoagulation Trial Study Group. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. N Engl J Med. 1995 Jun 22;332(25):1661-5. link to original article PubMed
Schulman S, Granqvist S, Holmström M, Carlsson A, Lindmarker P, Nicol P, Eklund SG, Nordlander S, Lärfars G, Leijd B, Linder O, Loogna E; The Duration of Anticoagulation Trial Study Group. The duration of oral anticoagulant therapy after a second episode of venous thromboembolism. N Engl J Med. 1997 Feb 6;336(6):393-8. link to original article PubMed
Kearon C, Gent M, Hirsh J, Weitz J, Kovacs MJ, Anderson DR, Turpie AG, Green D, Ginsberg JS, Wells P, MacKinnon B, Julian JA. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med. 1999 Mar 25;340(12):901-7. Erratum in: N Engl J Med 1999 Jul 22;341(4):298. link to original article PubMed
Agnelli G, Prandoni P, Santamaria MG, Bagatella P, Iorio A, Bazzan M, Moia M, Guazzaloca G, Bertoldi A, Tomasi C, Scannapieco G, Ageno W; Warfarin Optimal Duration Italian Trial Investigators. Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis. Warfarin Optimal Duration Italian Trial Investigators. N Engl J Med. 2001 Jul 19;345(3):165-9. link to original article PubMed
DOTAVK: Pinede L, Ninet J, Duhaut P, Chabaud S, Demolombe-Rague S, Durieu I, Nony P, Sanson C, Boissel JP; Investigators of the "Durée Optimale du Traitement AntiVitamines K" (DOTAVK) Study. Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep vein thrombosis or pulmonary embolism and comparison of 6 and 12 weeks of therapy after isolated calf deep vein thrombosis. Circulation. 2001 May 22;103(20):2453-60. link to original article PubMed
Agnelli G, Prandoni P, Becattini C, Silingardi M, Taliani MR, Miccio M, Imberti D, Poggio R, Ageno W, Pogliani E, Porro F, Zonzin P; Warfarin Optimal Duration Italian Trial Investigators. Extended oral anticoagulant therapy after a first episode of pulmonary embolism. Ann Intern Med. 2003 Jul 1;139(1):19-25. link to original article PubMed
SOFAST: Kearon C, Ginsberg JS, Anderson DR, Kovacs MJ, Wells P, Julian JA, Mackinnon B, Demers C, Douketis J, Turpie AG, Van Nguyen P, Green D, Kassis J, Kahn SR, Solymoss S, Desjardins L, Geerts W, Johnston M, Weitz JI, Hirsh J, Gent M; SOFAST Investigators. Comparison of 1 month with 3 months of anticoagulation for a first episode of venous thromboembolism associated with a transient risk factor. J Thromb Haemost. 2004 May;2(5):743-9. link to original article PubMed
LITE: Hull RD, Pineo GF, Brant RF, Mah AF, Burke N, Dear R, Wong T, Cook R, Solymoss S, Poon MC, Raskob G; LITE Trial Investigators. Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer. Am J Med. 2006 Dec;119(12):1062-72. link to original article PubMed
RE-COVER: Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H, Baanstra D, Schnee J, Goldhaber SZ; RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009 Dec 10;361(24):2342-52. link to original article contains dosing details in manuscript PubMed NCT00291330
EINSTEIN Acute DVT: Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, Gallus AS, Lensing AW, Misselwitz F, Prins MH, Raskob GE, Segers A, Verhamme P, Wells P, Agnelli G, Bounameaux H, Cohen A, Davidson BL, Piovella F, Schellong S; EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010 Dec 23;363(26):2499-510. Epub 2010 Dec 3. link to original article contains dosing details in manuscript PubMed NCT00440193; NCT00439725
EINSTEIN-PE: Büller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A; EINSTEIN-PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012 Apr 5;366(14):1287-97. Epub 2012 Mar 26. link to original article contains dosing details in abstract PubMed NCT00439777
RE-MEDY: Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, Kvamme AM, Friedman J, Mismetti P, Goldhaber SZ; RE-MEDY Trial Investigators; RE-SONATE Trial Investigators. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):709-18. link to original article PubMed NCT00329238
AMPLIFY: Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013 Aug 29;369(9):799-808. Epub 2013 Jul 1. link to original article contains dosing details in manuscript PubMed NCT00643201
Hokusai-VTE: Büller HR, Décousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, Shi M, Verhamme P, Wells P; Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013 Oct 10;369(15):1406-15. Epub 2013 Aug 31. Erratum in: N Engl J Med. 2014 Jan 23;370(4):390. link to original article contains dosing details in manuscript PubMed NCT00986154
1. Subgroup analysis: Raskob GE, van Es N, Segers A, Angchaisuksiri P, Oh D, Boda Z, Lyons RM, Meijer K, Gudz I, Weitz JI, Zhang G, Lanz H, Mercuri MF, Büller HR; Hokusai-VTE investigators. Edoxaban for venous thromboembolism in patients with cancer: results from a non-inferiority subgroup analysis of the Hokusai-VTE randomised, double-blind, double-dummy trial. Lancet Haematol. 2016 Aug;3(8):e379-87. Epub 2016 Jul 1. link to original article PubMed
RE-COVER II: Schulman S, Kakkar AK, Goldhaber SZ, Schellong S, Eriksson H, Mismetti P, Christiansen AV, Friedman J, Le Maulf F, Peter N, Kearon C; RE-COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014 Feb 18;129(7):764-72. Epub 2013 Dec 16. link to original article PubMed NCT00680186
CATCH: Lee AY, Kamphuisen PW, Meyer G, Bauersachs R, Janas MS, Jarner MF, Khorana AA; CATCH Investigators. Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: A randomized clinical trial. JAMA. 2015 Aug 18;314(7):677-86. link to original article PubMed NCT01130025

Additional information

↑ Circulation patient page about postthrombotic syndrome (PTS)

ACCP Chest guidelines for antithrombotic therapy for venous thromboembolic disease (2016)
ACCP Chest Guidelines (2012) - Antithrombotic Therapy and Prevention of Thrombosis, 9th edition (2012)
- Executive summary PDF
Bleeding risk on anticoagulation: HAS-BLED; HEMORR2HAGES

[1] Circulation patient page about postthrombotic syndrome (PTS)

[1]

@@ Line 6: / Line 6: @@
 ''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:'''
 *[[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<ref>[http://circ.ahajournals.org/content/121/8/e217.full Circulation patient page about postthrombotic syndrome (PTS)]</ref>
 {| class="wikitable" style="float:right; margin-right: 5px;"
 |-
@@ Line 20: / Line 18: @@
 =Guidelines=
 ==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]
 ==[https://www.asco.org/ ASCO]==
 *'''2019:''' Key et al. [https://doi.org/10.1200/JCO.19.01461 Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update.] [https://pubmed.ncbi.nlm.nih.gov/31381464 PubMed]
 ===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://doi.org/10.1200/JCO.2013.49.1118 Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update] [https://pubmed.ncbi.nlm.nih.gov/23669224 PubMed]
 *'''2007:''' Lyman et al. [https://doi.org/10.1200/JCO.2007.14.1283 American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer.] [https://pubmed.ncbi.nlm.nih.gov/17968019 PubMed]
 ==[https://www.hematology.org/ ASH]==
 *'''2021:''' Lyman et al. [https://doi.org/10.1182/bloodadvances.2020003442 American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer]
@@ Line 43: / Line 35: @@
 *'''2018:''' Bates et al. [http://www.bloodadvances.org/content/2/22/3317 American Society of Hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy]
 *'''2018:''' Cuker et al. [http://www.bloodadvances.org/content/2/22/3360 American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia]
 ==[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://pubmed.ncbi.nlm.nih.gov/20433989 PubMed]
 =="How I Treat"==
 *'''2022:''' Schmidt & Lee. [https://doi.org/10.1182/blood.2019003689 How I treat and prevent venous thrombotic complications in patients with lymphoma]
@@ Line 54: / Line 43: @@
 *'''2020:''' Wang & Carrier. [https://doi.org/10.1182/blood.2019003528 How I treat obese patients with oral anticoagulants]
 *'''2019:''' Pabinger & Thaler. [https://doi.org/10.1182/blood.2019002927 How I treat patients with hereditary antithrombin deficiency]
 ==IMWG==
 ===Current===
 *[https://www.myeloma.org/resource-library/imwg-guidelines-prevention-thalidomide-lenalidomide-associated-thrombosis-myeloma IMWG guidelines for the prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma]
 ===Older===
 *'''2007:''' [https://doi.org/10.1038/sj.leu.2405062 Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma] [https://pubmed.ncbi.nlm.nih.gov/18094721 PubMed]
 ==ITAC (International Initiative on Thrombosis and Cancer)==
 *'''2022:''' Farge et al. [https://doi.org/10.1016/S1470-2045(22)00160-7 2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19]
@@ Line 70: / Line 54: @@
 *'''2016:''' Farge et al. [https://doi.org/10.1016/S1470-2045(16)30369-2 International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer] [https://pubmed.ncbi.nlm.nih.gov/27733271 PubMed]
 *'''2013:''' Farge et al. [https://doi.org/10.1111/jth.12070 International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer]
 =VTE primary prophylaxis=
 ==Apixaban monotherapy {{#subobject:9958a4|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 10-14 days post-op {{#subobject:734aaa|Variant=1}}===
 {| class="wikitable" style="color:white; background-color:#404040"
@@ Line 99: / Line 82: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *Total knee replacement
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Apixaban (Eliquis)]] 2.5 mg PO twice per day, beginning 12 to 24 h after wound closure
 '''10- to 14-day course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 35 days post-op {{#subobject:15ab8c|Variant=1}}===
 {| class="wikitable" style="color:white; background-color:#404040"
@@ Line 128: / Line 111: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *Total hip replacement
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Apixaban (Eliquis)]] 2.5 mg PO twice per day, beginning 12 to 24 h after wound closure
 '''35-day course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #3, 180 days {{#subobject:15cd2c|Variant=1}}===
 {| class="wikitable" style="color:white; background-color:#404040"
@@ Line 157: / Line 140: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Apixaban (Eliquis)]] 2.5 mg PO twice per day, beginning within 24 h of initiation of chemotherapy
 '''6-month course'''
+</div></div>
 ===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://doi.org/10.1056/NEJMoa0810773 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19657123 PubMed] NCT00371683
 #'''ADVANCE-2:''' Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P; ADVANCE-2 investigators. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet. 2010 Mar 6;375(9717):807-15. [https://doi.org/10.1016/S0140-6736(09)62125-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20206776 PubMed] NCT00452530
 #'''ADVANCE-3:''' Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM; ADVANCE-3 Investigators. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med. 2010 Dec 23;363(26):2487-98. [https://doi.org/10.1056/NEJMoa1006885 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21175312 PubMed] NCT00423319
 #'''AVERT:''' Carrier M, Abou-Nassar K, Mallick R, Tagalakis V, Shivakumar S, Schattner A, Kuruvilla P, Hill D, Spadafora S, Marquis K, Trinkaus M, Tomiak A, Lee AYY, Gross PL, Lazo-Langner A, El-Maraghi R, Goss G, Le Gal G, Stewart D, Ramsay T, Rodger M, Witham D, Wells PS; AVERT Investigators. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med. 2019 Feb 21;380(8):711-719. Epub 2018 Dec 4. [https://doi.org/10.1056/NEJMoa1814468 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30511879 PubMed] NCT02048865
 ==Aspirin monotherapy {{#subobject:2b1389|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:e721b6|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 210: / Line 190: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Aspirin]] 81 to 160 mg PO once per day
 '''Various durations, see individual trials'''
+</div></div>
 ===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://doi.org/10.1016/S0140-6736(00)02110-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10776741 PubMed]
 #'''ECLAP:''' Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, Barbui T; European Collaboration on Low-Dose Aspirin in Polycythemia Vera Investigators. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004 Jan 8;350(2):114-24. [https://doi.org/10.1056/nejmoa035572 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14711910 PubMed]
@@ Line 223: / Line 202: @@
 #'''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://pubmed.ncbi.nlm.nih.gov/23732713 PubMed] ISRCTN11902170
 #'''EPCAT II:''' Anderson DR, Dunbar M, Murnaghan J, Kahn SR, Gross P, Forsythe M, Pelet S, Fisher W, Belzile E, Dolan S, Crowther M, Bohm E, MacDonald SJ, Gofton W, Kim P, Zukor D, Pleasance S, Andreou P, Doucette S, Theriault C, Abianui A, Carrier M, Kovacs MJ, Rodger MA, Coyle D, Wells PS, Vendittoli PA. Aspirin or rivaroxaban for VTE prophylaxis after hip or knee arthroplasty. N Engl J Med. 2018 Feb 22;378(8):699-707. [https://doi.org/10.1056/NEJMoa1712746 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29466159 PubMed] NCT01720108
 ==Betrixaban monotherapy {{#subobject:834d5c|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:f70ffb|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 240: / Line 218: @@
 |}
 ''Note: this APEX trial should not be confused with the one in multiple myeloma.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Betrixaban (Bevyxxa)]] 80 mg PO once per day
+</div></div>
 ===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://doi.org/10.1056/NEJMoa1601747 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27232649 PubMed] NCT01583218
 ==Enoxaparin monotherapy {{#subobject:f7bdac|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 30 mg every 12 hours {{#subobject:a4d4d8|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 270: / Line 246: @@
 | style="background-color:#fc8d59" |Seems to have higher bleeding rate
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *ADVANCE-1: Total knee replacement
 *The study population in Geerts et. al. were trauma patients without intracranial hemorrhage. Prophylaxis was initiated within 36 hours of the injury.
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====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.
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 40 mg daily {{#subobject:8e940e|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 364: / Line 341: @@
 |}
 ''Note: the APEX trial here should not be confused with the one in multiple myeloma.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *ADVANCE-2 & CRISTAL: Total knee replacement
 *ADVANCE-3 & CRISTAL: Total hip replacement
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Enoxaparin (Lovenox)]] 40 mg SC once per day
 '''Various durations (see papers for details)'''
+</div></div>
 ===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://doi.org/10.1056/NEJM199609053351003 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8703169 PubMed]
 #'''MEDENOX:''' Samama MM, Cohen AT, Darmon JY, Desjardins L, Eldor A, Janbon C, Leizorovicz A, Nguyen H, Olsson CG, Turpie AG, Weisslinger N; MEDENOX Investigators. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. N Engl J Med. 1999; 341:793-800. [https://doi.org/10.1056/NEJM199909093411103 link to original article]. [https://pubmed.ncbi.nlm.nih.gov/10477777 PubMed].
@@ Line 394: / Line 369: @@
 #'''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://doi.org/10.1056/NEJMoa1601747 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27232649 PubMed] NCT01583218
 #'''CRISTAL:''' Sidhu VS, Kelly TL, Pratt N, Graves SE, Buchbinder R, Adie S, Cashman K, Ackerman I, Bastiras D, Brighton R, Burns AWR, Chong BH, Clavisi O, Cripps M, Dekkers M, de Steiger R, Dixon M, Ellis A, Griffith EC, Hale D, Hansen A, Harris A, Hau R, Horsley M, James D, Khorshid O, Kuo L, Lewis P, Lieu D, Lorimer M, MacDessi S, McCombe P, McDougall C, Mulford J, Naylor JM, Page RS, Radovanovic J, Solomon M, Sorial R, Summersell P, Tran P, Walter WL, Webb S, Wilson C, Wysocki D, Harris IA; CRISTAL Study Group. Effect of Aspirin vs Enoxaparin on Symptomatic Venous Thromboembolism in Patients Undergoing Hip or Knee Arthroplasty: The CRISTAL Randomized Trial. JAMA. 2022 Aug 23;328(8):719-727. [https://doi.org/10.1001/jama.2022.13416 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35997730/ PubMed] ACTRN12618001879257
 ==Placebo==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 431: / Line 405: @@
 |}
 ''No active treatment.''
+</div></div>
 ===References===
 #Gärdlund B; 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://doi.org/10.1016/s0140-6736(96)91009-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/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://pubmed.ncbi.nlm.nih.gov/20621900 PubMed] NCT00077753
@@ Line 438: / Line 412: @@
 #'''MARINER:''' Spyropoulos AC, Ageno W, Albers GW, Elliott CG, Halperin JL, Hiatt WR, Maynard GA, Steg PG, Weitz JI, Suh E, Spiro TE, Barnathan ES, Raskob GE; MARINER Investigators. Rivaroxaban for thromboprophylaxis after hospitalization for medical illness. N Engl J Med. 2018 Sep 20;379(12):1118-1127. Epub 2018 Aug 26. [https://doi.org/10.1056/NEJMoa1805090 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30145946 PubMed] NCT02111564
 #'''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://doi.org/10.1056/NEJMoa1814630 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30786186 PubMed] NCT02555878
 ==Rivaroxaban monotherapy {{#subobject:6a7fba|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:828315|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 484: / Line 457: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Rivaroxaban (Xarelto)]] 10 mg PO once per day for varying durations (see individual studies)
+</div></div>
 ===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://doi.org/10.1016/S0140-6736(08)60880-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18582928 PubMed] NCT00332020
 #'''RECORD1:''' Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, Bandel TJ, Beckmann H, Muehlhofer E, Misselwitz F, Geerts W; RECORD1 Study Group. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008 Jun 26;358(26):2765-75. [https://doi.org/10.1056/NEJMoa0800374 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18579811 PubMed] NCT00329628
@@ Line 497: / Line 469: @@
 #'''EPCAT II:''' Anderson DR, Dunbar M, Murnaghan J, Kahn SR, Gross P, Forsythe M, Pelet S, Fisher W, Belzile E, Dolan S, Crowther M, Bohm E, MacDonald SJ, Gofton W, Kim P, Zukor D, Pleasance S, Andreou P, Doucette S, Theriault C, Abianui A, Carrier M, Kovacs MJ, Rodger MA, Coyle D, Wells PS, Vendittoli PA. Aspirin or rivaroxaban for VTE prophylaxis after hip or knee arthroplasty. N Engl J Med. 2018 Feb 22;378(8):699-707. [https://doi.org/10.1056/NEJMoa1712746 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29466159 PubMed] NCT01720108
 #'''MARINER:''' Spyropoulos AC, Ageno W, Albers GW, Elliott CG, Halperin JL, Hiatt WR, Maynard GA, Steg PG, Weitz JI, Suh E, Spiro TE, Barnathan ES, Raskob GE; MARINER Investigators. Rivaroxaban for thromboprophylaxis after hospitalization for medical illness. N Engl J Med. 2018 Sep 20;379(12):1118-1127. Epub 2018 Aug 26. [https://doi.org/10.1056/NEJMoa1805090 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30145946 PubMed] NCT02111564
 =VTE secondary prevention=
 ==Apixaban monotherapy {{#subobject:94eb02|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 2.5 mg twice per day {{#subobject:969d50|Variant=1}}===
 {| class="wikitable" style="color:white; background-color:#404040"
@@ Line 521: / Line 492: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *Therapeutic anticoagulation x 6-12 mo
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Apixaban (Eliquis)]] 2.5 mg PO twice per day
 '''12-month course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 5 mg twice per day {{#subobject:c7bfff0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 547: / Line 518: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *Therapeutic anticoagulation x 6-12 mo
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Apixaban (Eliquis)]] 5 mg PO twice per day
 '''12-month course'''
+</div></div>
 ===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://doi.org/10.1056/NEJMoa1207541 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23216615 PubMed]
 ==Aspirin monotherapy {{#subobject:eb5633|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:e3079b|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 585: / Line 553: @@
 |}
 ''Note: ASPIRE should not be confused with the multiple myeloma trial of the same name.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *WARFASA: [[#Warfarin_monotherapy|Warfarin]] x 6 to 18 months
 *ASPIRE: [[#Warfarin_monotherapy|Warfarin]] x 6 weeks to 24 months
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Aspirin]] 100 mg PO once per day
 '''Two or more years'''
+</div></div>
 ===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://doi.org/10.1056/NEJMoa1114238 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22621626 PubMed] NCT00222677
 #'''ASPIRE-VTE:''' Brighton TA, Eikelboom JW, Mann K, Mister R, Gallus A, Ockelford P, Gibbs H, Hague W, Xavier D, Diaz R, Kirby A, Simes J; ASPIRE Investigators. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med. 2012 Nov 22;367(21):1979-87. Epub 2012 Nov 4. [https://doi.org/10.1056/NEJMoa1210384 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23121403 PubMed] ACTRN12605000004662
 ==Dalteparin monotherapy {{#subobject:57c5b7|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:cbc29a|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 618: / Line 583: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====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'''
+</div></div>
 ===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://doi.org/10.1056/NEJMoa025313 link to original article] [https://pubmed.ncbi.nlm.nih.gov/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. [https://doi.org/10.1200/jco.2005.03.133 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15699480 PubMed]
 ==Enoxaparin monotherapy {{#subobject:30d50d|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:a64a42|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 645: / Line 608: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Enoxaparin (Lovenox)]] 1.5 mg/kg SC once per day
 '''3-month course'''
+</div></div>
 ===References===
 #Decousus H, Leizorovicz A, Parent F, Page Y, Tardy B, Girard P, Laporte S, Faivre R, Charbonnier B, Barral FG, Huet Y, Simonneau G; Prévention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group. A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. N Engl J Med. 1998 Feb 12;338(7):409-15. [https://doi.org/10.1056/nejm199802123380701 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9459643/ PubMed]
 #Meyer G, Marjanovic Z, Valcke J, Lorcerie B, Gruel Y, Solal-Celigny P, Le Maignan C, Extra JM, Cottu P, Farge D. Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. Arch Intern Med. 2002 Aug 12-26;162(15):1729-35. [http://archinte.jamanetwork.com/article.aspx?articleid=754085 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12153376 PubMed]
 ==Warfarin monotherapy {{#subobject:acc688|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, standard intensity {{#subobject:3eda79|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 677: / Line 639: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Warfarin (Coumadin)]] PO titrated to goal INR 2 to 3.0
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, low intensity {{#subobject:7c40af|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 696: / Line 659: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *Warfarin with goal INR of 2 to 3 for median of 6.5 mo
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Warfarin (Coumadin)]] PO titrated to goal INR 1.5 to 2.0
 '''Continued indefinitely'''
+</div></div>
 ===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://pubmed.ncbi.nlm.nih.gov/12153376 PubMed]
 #Kearon C, Ginsberg JS, Kovacs MJ, Anderson DR, Wells P, Julian JA, MacKinnon B, Weitz JI, Crowther MA, Dolan S, Turpie AG, Geerts W, Solymoss S, van Nguyen P, Demers C, Kahn SR, Kassis J, Rodger M, Hambleton J, Gent M; Extended Low-Intensity Anticoagulation for Thrombo-Embolism Investigators. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med. 2003 Aug 14;349(7):631-9. [https://doi.org/10.1056/nejmoa035422 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12917299/ PubMed]
@@ Line 713: / Line 674: @@
 #'''CLOT:''' Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M; Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003 Jul 10;349(2):146-53. [https://doi.org/10.1056/NEJMoa025313 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12853587 PubMed]
 ##'''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. [https://doi.org/10.1200/jco.2005.03.133 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15699480 PubMed]
 =VTE treatment, all lines of therapy=
 ==Apixaban monotherapy {{#subobject:f80057|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:856942|Variant=1}}===
 {| class="wikitable" style="color:white; background-color:#404040"
@@ Line 742: / Line 702: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Apixaban (Eliquis)]] 10 mg PO twice per day for 7 days, then 5 mg PO twice per day
 '''6-month course'''
+</div></div>
 ===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://doi.org/10.1056/NEJMoa1302507 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23808982 PubMed] NCT00643201
 #'''CARAVAGGIO:''' Agnelli G, Becattini C, Meyer G, Munoz A, Huisman M, Connors J, Cohen A, Bauersachs R, Brenner B, Torbicki A, Sueiro M, Lambert C, Gussoni G, Campanini M, Fontanella A, Vescovo G, Verso M, Caravaggio Investigators. Apixaban for the treatment of venous thromboembolism associated with cancer. N Engl J Med. 2020 Apr 23;382(17):1599-1607. Epub 2020 Mar 29. [https://doi.org/10.1056/NEJMoa1915103 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32223112/ PubMed] NCT03045406
 ==Argatroban monotherapy {{#subobject:8171b3|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:3f6d7f|Variant=1}}===
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Argatroban (Acova)]]
+</div></div>
 ===References===
 To be completed
 ==Aspirin monotherapy {{#subobject:0481f0|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:0113df|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 784: / Line 740: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *6 to 12 months of a vitamin K antagonist or a direct oral anticoagulant
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Aspirin]] 100 mg PO once per day
 '''Up to 12-month course'''
+</div></div>
 ===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://doi.org/10.1056/NEJMoa1700518 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28316279 PubMed] NCT02064439
 ==Bivalirudin monotherapy {{#subobject:5a08f6|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:5faf02|Variant=1}}===
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Bivalirudin (Angiomax)]]
+</div></div>
 ===References===
 To be completed
 ==Dabigatran monotherapy {{#subobject:4b48cf|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:518855|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 823: / Line 777: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Dabigatran (Pradaxa)]] 150 mg PO twice per day
 '''6-month course'''
+</div></div>
 ===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://doi.org/10.1056/NEJMoa0906598 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19966341 PubMed] NCT00291330
 #'''RE-MEDY:''' Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, Kvamme AM, Friedman J, Mismetti P, Goldhaber SZ; RE-MEDY Trial Investigators; RE-SONATE Trial Investigators. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):709-18. [https://doi.org/10.1056/NEJMoa1113697 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23425163 PubMed] NCT00329238
 #'''RE-COVER II:''' Schulman S, Kakkar AK, Goldhaber SZ, Schellong S, Eriksson H, Mismetti P, Christiansen AV, Friedman J, Le Maulf F, Peter N, Kearon C; RE-COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014 Feb 18;129(7):764-72. Epub 2013 Dec 16. [http://circ.ahajournals.org/content/129/7/764.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/24344086 PubMed] NCT00680186
 #'''DIVERSITY:''' Halton J, Brandão LR, Luciani M, Bomgaars L, Chalmers E, Mitchell LG, Nurmeev I, Sharathkumar A, Svirin P, Gorbatikov K, Tartakovsky I, Simetzberger M, Huang F, Sun Z, Kreuzer J, Gropper S, Reilly P, Brueckmann M, Albisetti M; DIVERSITY Trial Investigators. Dabigatran etexilate for the treatment of acute venous thromboembolism in children (DIVERSITY): a randomised, controlled, open-label, phase 2b/3, non-inferiority trial. Lancet Haematol. 2021 Jan;8(1):e22-e33. Epub 2020 Dec 5. [https://doi.org/10.1016/s2352-3026(20)30368-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33290737/ PubMed] NCT01895777
 ==Dalteparin monotherapy {{#subobject:4a96a1|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:afbbc0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 870: / Line 822: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Dalteparin (Fragmin)]] as follows:
 **First month: 200 IU/kg once per day
 **Month 2 onwards: 150 IU/kg once per day
 '''6- to 12-month course'''
+</div></div>
 ===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://doi.org/10.1111/jth.12923 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25827941 PubMed] NCT00942968
 #'''Hokusai VTE Cancer:''' Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia D, Grosso MA, Kakkar AK, Kovacs MJ, Mercuri MF, Meyer G, Segers A, Shi M, Wang TF, Yeo E, Zhang G, Zwicker JI, Weitz JI, Büller HR; Hokusai VTE Cancer Investigators. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med. 2018 Feb 15;378(7):615-624. Epub 2017 Dec 12. [https://doi.org/10.1056/NEJMoa1711948 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29231094 PubMed] NCT02073682
 #'''SELECT-D:''' Young AM, Marshall A, Thirlwall J, Chapman O, Lokare A, Hill C, Hale D, Dunn JA, Lyman GH, Hutchinson C, MacCallum P, Kakkar A, Hobbs FDR, Petrou S, Dale J, Poole CJ, Maraveyas A, Levine M. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol. 2018 Jul 10;36(20):2017-2023. Epub 2018 May 10. [https://doi.org/10.1200/JCO.2018.78.8034 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29746227 PubMed] ISRCTN86712308
 #'''CARAVAGGIO:''' Agnelli G, Becattini C, Meyer G, Munoz A, Huisman M, Connors J, Cohen A, Bauersachs R, Brenner B, Torbicki A, Sueiro M, Lambert C, Gussoni G, Campanini M, Fontanella A, Vescovo G, Verso M, Caravaggio Investigators. Apixaban for the treatment of venous thromboembolism associated with cancer. N Engl J Med. 2020 Apr 23;382(17):1599-1607. Epub 2020 Mar 29. [https://doi.org/10.1056/NEJMoa1915103 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32223112/ PubMed] NCT03045406
 ==Edoxaban monotherapy {{#subobject:d0ebe7|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, reduced dose {{#subobject:5c53d8|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 908: / Line 858: @@
 |}
 ''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]].''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *Therapeutic dose [[:Category:Low molecular weight heparins|LMWH]] for at least 5 days, then:
 *[[Edoxaban (Savaysa)]] 30 mg PO once per day
 '''3- to 12-month course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, normal dosing {{#subobject:88a424|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 936: / Line 886: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *Therapeutic dose [[:Category:Low molecular weight heparins|LMWH]] for at least 5 days, then:
 *[[Edoxaban (Savaysa)]] 60 mg PO once per day
 '''3- to 12-month course'''
+</div></div>
 ===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://doi.org/10.1056/NEJMoa1306638 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23991658 PubMed] NCT00986154
 ##'''Subgroup analysis:''' Raskob GE, van Es N, Segers A, Angchaisuksiri P, Oh D, Boda Z, Lyons RM, Meijer K, Gudz I, Weitz JI, Zhang G, Lanz H, Mercuri MF, Büller HR; Hokusai-VTE investigators. Edoxaban for venous thromboembolism in patients with cancer: results from a non-inferiority subgroup analysis of the Hokusai-VTE randomised, double-blind, double-dummy trial. Lancet Haematol. 2016 Aug;3(8):e379-87. Epub 2016 Jul 1. [https://doi.org/10.1016/S2352-3026(16)30057-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27476789 PubMed]
 #'''Hokusai VTE Cancer:''' Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia D, Grosso MA, Kakkar AK, Kovacs MJ, Mercuri MF, Meyer G, Segers A, Shi M, Wang TF, Yeo E, Zhang G, Zwicker JI, Weitz JI, Büller HR; Hokusai VTE Cancer Investigators. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med. 2018 Feb 15;378(7):615-624. Epub 2017 Dec 12. [https://doi.org/10.1056/NEJMoa1711948 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29231094 PubMed] NCT02073682
 ==Enoxaparin monotherapy {{#subobject:fc9e30|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:5a4974|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 962: / Line 910: @@
 | style="background-color:#eeee01" |No difference in recurrent VTE or major bleeding
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Enoxaparin (Lovenox)]] SC 100 IU/kg every 12 hours
+</div></div>
 ===References===
 #'''FIDO:''' Kearon C, Ginsberg JS, Julian JA, Douketis J, Solymoss S, Ockelford P, Jackson S, Turpie AG, MacKinnon B, Hirsh J, Gent M; Fixed-Dose Heparin (FIDO) Investigators. Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism. JAMA. 2006 Aug 23;296(8):935-42. [https://jamanetwork.com/journals/jama/fullarticle/203221 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16926353 PubMed] NCT00182403
 ==Fondaparinux monotherapy {{#subobject:7a8cb8|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:ab5c25|Variant=1}}===
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Fondaparinux (Arixtra)]]
+</div></div>
 ===References===
 To be completed
 ==Heparin monotherapy {{#subobject:2a8be8|Regimen=1}}==
 UFH: '''<u>U</u>'''n'''<u>F</u>'''ractionated '''<u>H</u>'''eparin
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:8cae03|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,002: / Line 946: @@
 |}
 ''Note: In Loewe and Hirsch, heparin was administered as a deep subcutaneous injection (200 to 400 mg / 200,000 to 400,000 IU) in Pitkin menstruum every two to three days for 10 to 14 days for deep vein thrombosis and extended for one to two additional weeks for pulmonary embolism.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Unfractionated heparin (UFH)]] SC 333 units/kg once, then 250 units/kg every 12 hours
+</div></div>
 ===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://pubmed.ncbi.nlm.nih.gov/20293012 PubMed]
 #'''FIDO:''' Kearon C, Ginsberg JS, Julian JA, Douketis J, Solymoss S, Ockelford P, Jackson S, Turpie AG, MacKinnon B, Hirsh J, Gent M; Fixed-Dose Heparin (FIDO) Investigators. Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism. JAMA. 2006 Aug 23;296(8):935-42. [https://jamanetwork.com/journals/jama/fullarticle/203221 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16926353 PubMed] NCT00182403
 ==Lepirudin monotherapy {{#subobject:b61e00|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:22918f|Variant=1}}===
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Lepirudin (Refludan)]]
+</div></div>
 ===References===
 To be completed
 ==Rivaroxaban monotherapy {{#subobject:f435a7|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 10 mg/day {{#subobject:4f1fdf|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,042: / Line 983: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *6 to 12 months of a vitamin K antagonist or a direct oral anticoagulant
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Rivaroxaban (Xarelto)]] 10 mg PO once per day
 '''Up to 12-month course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 20 mg/day {{#subobject:ba11d9|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,071: / Line 1,012: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *6 to 12 months of a vitamin K antagonist or a direct oral anticoagulant
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Rivaroxaban (Xarelto)]] 20 mg PO once per day
 '''Up to 12-month course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #3, 20 mg/day with loading dose {{#subobject:ba11d9|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,108: / Line 1,049: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====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'''
+</div></div>
 ===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://doi.org/10.1056/NEJMoa1007903 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21128814 PubMed] NCT00440193; NCT00439725
 #'''EINSTEIN-PE:''' Büller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A; EINSTEIN-PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012 Apr 5;366(14):1287-97. Epub 2012 Mar 26. [https://doi.org/10.1056/NEJMoa1113572 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22449293 PubMed] NCT00439777
@@ Line 1,122: / Line 1,061: @@
 #'''SELECT-D:''' Young AM, Marshall A, Thirlwall J, Chapman O, Lokare A, Hill C, Hale D, Dunn JA, Lyman GH, Hutchinson C, MacCallum P, Kakkar A, Hobbs FDR, Petrou S, Dale J, Poole CJ, Maraveyas A, Levine M. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol. 2018 Jul 10;36(20):2017-2023. Epub 2018 May 10. [https://doi.org/10.1200/JCO.2018.78.8034 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29746227 PubMed] ISRCTN86712308
 #'''EINSTEIN Junior:''' Male C, Lensing AWA, Palumbo JS, Kumar R, Nurmeev I, Hege K, Bonnet D, Connor P, Hooimeijer HL, Torres M, Chan AKC, Kenet G, Holzhauer S, Santamaría A, Amedro P, Chalmers E, Simioni P, Bhat RV, Yee DL, Lvova O, Beyer-Westendorf J, Biss TT, Martinelli I, Saracco P, Peters M, Kállay K, Gauger CA, Massicotte MP, Young G, Pap AF, Majumder M, Smith WT, Heubach JF, Berkowitz SD, Thelen K, Kubitza D, Crowther M, Prins MH, Monagle P; EINSTEIN-Jr Phase 3 Investigators. Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial. Lancet Haematol. 2020 Jan;7(1):e18-e27. Epub 2019 Nov 5. [https://doi.org/10.1016/s2352-3026(19)30219-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31699660/ PubMed] NCT02234843
 ==Tinzaparin monotherapy {{#subobject:3d9d84|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:24b40c|Variant=1}}===
 ''Note: this agent has been withdrawn from the US market.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Tinzaparin (Innohep)]]
+</div></div>
 ===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 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17145251 PubMed]
 #'''CATCH:''' Lee AY, Kamphuisen PW, Meyer G, Bauersachs R, Janas MS, Jarner MF, Khorana AA; CATCH Investigators. Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: A randomized clinical trial. JAMA. 2015 Aug 18;314(7):677-86. [http://jama.jamanetwork.com/article.aspx?articleid=2428955 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26284719 PubMed] NCT01130025
 ==Warfarin monotherapy {{#subobject:76610c|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:cd707c|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,183: / Line 1,119: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Anticoagulation====
 *[[Warfarin (Coumadin)]] with goal INR between 2 and 3.0
 ====Supportive therapy====
 *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)'''
+</div></div>
 ===References===
 #Schulman S, Rhedin AS, Lindmarker P, Carlsson A, Lärfars G, Nicol P, Loogna E, Svensson E, Ljungberg B, Walter H; Duration of Anticoagulation Trial Study Group. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. N Engl J Med. 1995 Jun 22;332(25):1661-5. [https://doi.org/10.1056/nejm199506223322501 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7760866/ PubMed]
@@ Line 1,210: / Line 1,144: @@
 #'''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://pubmed.ncbi.nlm.nih.gov/24344086 PubMed] NCT00680186
 #'''CATCH:''' Lee AY, Kamphuisen PW, Meyer G, Bauersachs R, Janas MS, Jarner MF, Khorana AA; CATCH Investigators. Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: A randomized clinical trial. JAMA. 2015 Aug 18;314(7):677-86. [https://doi.org/10.1001/jama.2015.9243 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26284719 PubMed] NCT01130025
 =Additional information=
 <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/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/article.aspx?articleID=1159399 Executive summary] [http://journal.publications.chestnet.org/data/Journals/CHEST/23443/chest_141_2_suppl_7S.pdf PDF]
 *Bleeding risk on anticoagulation: [http://www.globalrph.com/has-bled-score.htm HAS-BLED]; [http://www.globalrph.com/hemorr2hages-bleeding-risk.htm HEMORR2HAGES]
 [[Category:Venous thromboembolism regimens]]
 [[Category:Disease-specific pages]]
 [[Category:Thrombotic disorders]]

Difference between revisions of "Venous thromboembolism"

Revision as of 12:32, 14 October 2022

Guidelines

ACCP

ASCO

Older

ASH

ESMO

"How I Treat"

IMWG

Current

Older

ITAC (International Initiative on Thrombosis and Cancer)

Older

VTE primary prophylaxis

Apixaban monotherapy

Regimen variant #1, 10-14 days post-op

Preceding treatment

Anticoagulation

Regimen variant #2, 35 days post-op

Preceding treatment

Anticoagulation

Regimen variant #3, 180 days

Anticoagulation

References

Aspirin monotherapy

Regimen

Anticoagulation

References

Betrixaban monotherapy

Regimen

Anticoagulation

References

Enoxaparin monotherapy

Regimen variant #1, 30 mg every 12 hours

Preceding treatment

Anticoagulation

Regimen variant #2, 40 mg daily

Preceding treatment

Anticoagulation

References

Placebo

Regimen

References

Rivaroxaban monotherapy

Regimen

Anticoagulation

References

VTE secondary prevention

Apixaban monotherapy

Regimen variant #1, 2.5 mg twice per day

Preceding treatment

Anticoagulation

Regimen variant #2, 5 mg twice per day

Preceding treatment

Anticoagulation

References

Aspirin monotherapy

Regimen

Preceding treatment

Anticoagulation

References

Dalteparin monotherapy

Regimen

Anticoagulation

References

Enoxaparin monotherapy

Regimen

Anticoagulation

References

Warfarin monotherapy

Regimen variant #1, standard intensity

Anticoagulation

Regimen variant #2, low intensity

Preceding treatment

Anticoagulation

References

VTE treatment, all lines of therapy

Apixaban monotherapy

Regimen