Anticoagulation after venous thromboembolism

Summary

Deciding on the optimal duration of anticoagulation is based on the risk of recurrent venous thromboembolism (VTE) and of bleeding during anticoagulation. The duration of anticoagulation should be at least three months since shorter courses double the recurrence rates.

At three months anticoagulation can be stopped in patients with a VTE provoked by a transient risk factor, as the recurrence risk is expected to be lower than the bleeding risk during anticoagulation. Patients with unprovoked VTE are at higher risk of recurrence and prolonged anticoagulation is currently recommended.

However, attempts are made to stratify these patients according to their recurrence risk and to identify those with a low recurrence risk who would not benefit from extended anticoagulation. Novel approaches to optimize the management of patients with unprovoked VTE are the use of prediction models which link clinical patient characteristics with laboratory testing to discriminate between patients with a low risk (who may discontinue anticoagulation) and those with high risk (in whom long term anticoagulation is justified). Moreover, new antithrombotic concepts including new oral anticoagulants or aspirin both of which potentially confer a lower bleeding risk and are more convenient for the patients have been explored for extended thromboprophylaxis.

Zusammenfassung

Die venöse Thromboembolie (VTE) ist eine häufige und chronische Erkrankung mit hohem Rezidivrisiko. Ein Rezidiv kann durch eine Antikoagulanzientherapie verhindert werden, die jedoch ein Blutungsrisiko mit sich bringt. Die optimale Dauer der Antikoagulation leitet sich daher vom Verhältnis des Rezidivrisikos zum Blutungsrisiko ab.

Patienten mit einer VTE, die im Zusammenhang mit einem transienten Risikofaktor aufgetreten ist, haben ein niedriges Rezidivrisiko. In diesem Fällen ist eine dreimonatige Antikoagulation ausreichend, da sonst das Risiko der Blutung das des Rezidivs überwiegen würde. Patienten mit einer spontanen VTE haben ein höheres Rezidivrisiko und eine längerfristige Antikoagulation sollte erwogen werden. Die meisten dieser Patienten werden dennoch kein Rezidiv erleiden.

Es ist zurzeit jedoch nicht möglich, Patienten mit einem hohen oder niedrigen Rezidivrisiko sicher voneinander zu unterscheiden. Durch die Bestimmung des D-Dimers oder die Verwendung von Vorhersagemodellen könnte das Rezidivrisiko auch bei Patienten mit spontaner VTE besser abgeschätzt werden und somit die Entscheidung über die optimale Dauer der Antikoagulation verbessert werden. Neue orale Antikoagulanzien und auch Aspirin wurden für die Behandlung von Patienten mit VTE überprüft. Zusätzliche Daten vor allem über das Blutungsrisiko sind notwendig, um zu entscheiden, welche Patienten nun tatsächlich von diesen neuen Substanzen profitieren könnten.

Keywords

Venous thrombosis - recurrence - Vienna prediction model

Schlüsselwörter

Venenthrombose - Rezidivrisiko - Antikoagulation - Vorhersagemodelle

• References

• 1 Naess IA, Christiansen SC, Romundstad P. et al. Incidence and mortality of venous thromboembolism: a population-based study. J Thromb Haemost 2007; 05: 692-699.
• 2 Kyrle PA, Eichinger S. Deep vein thrombosis. Lancet 2005; 365: 1163-1174.
• 3 Murin S, Romano PS, White RH. Comparison of outcomes after hospitalization for deep venous thrombosis or pulmonary embolism. Thromb Haemost 2002; 88: 407-414.
• 4 Kyrle PA, Rosendaal FR, Eichinger S. Risk assessment for recurrent venous thrombosis. Lancet 2010; 376: 2032-2039.
• 5 Douketis JD, Gu CS, Schulman S. et al. The risk for fatal pulmonary embolism after discontinuing anticoagulant therapy for venous thromboembolism. Ann Intern Med 2007; 147: 766-774.
• 6 Carrier M, Le Gal G, Wells PS, Rodger MA. Systematic review: case-fatality rates of recurrent venous thromboembolism and major bleeding events among patients treated for venous thromboembolism. Ann Intern Med 2010; 152: 578-589.
• 7 Kearon C, Akl EA, Comerota AJ. et al. American College of Chest Physicians. Antithrombotic therapy for venous thromboembolic disease. Chest 2012; 141: e419S-e494S.
• 8 AWMF-Leitlinie Diagnostik und Therapie der Venenthrombose und der Lungenembolie (VTE). www.awmf.org.
• 9 EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363: 2499-2510.
• 10 EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012; 366: 1287-1297.
• 11 Schulman S, Kearon C, Kakkar AK. et al. RECOVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009; 361: 2342-2352.
• 12 Schulman S, Rhedin AS, Lindmarker P. et al. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. N Engl J Med 1995; 332: 1661-1665.
• 13 Kearon C, Ginsberg JS, Anderson DR. et al. 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; 02: 743-749.
• 14 Agnelli G, Prandoni P, Becattini C. et al. Warfarin Optimal Duration Italian Trial Investigators. Extended oral anticoagulant therapy after a first episode of pulmonary embolism. Ann Intern Med 2003; 139: 19-25.
• 15 Agnelli G, Prandoni P, Santamaria MG. et al. Warfarin Optimal Duration Italian Trial Investigators. Three months versus one year of oral anticoagulant therapy for idiopathic deep vein thrombosis. N Engl J Med 2001; 345: 165-169.
• 16 Campbell IA, Bentley DP, Prescott RJ. et al. Anticoagulation for three versus six months in patients with deep vein thrombosis or pulmonary embolism, or both. BMJ 2007; 334: 674-680.
• 17 Kearon C, Gent M, Hirsh J. et al. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med 1999; 340: 901-907.
• 18 Pinede L, Ninet J, Duhaut P. et al. for the Investigators of the Duree 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; 103: 2453-2460.
• 19 Ridker PM, Goldhaber SZ, Danielson E. et al. PREVENT Investigators. Long-term, low-intensity warfarin therapy for prevention of recurrent venous thromboembolism. N Engl J Med 2003; 348: 1425-1434.
• 20 Schulman S, Granqvist S, Holmström M. et al. The duration of oral anticoagulant therapy after a second episode of venous thromboembolism. N Engl J Med 1997; 336: 393-398.
• 21 Boutitie F, Pinede L, Schulman S. et al. Influence of preceding length of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping treatment. BMJ. 2011 24. 342:d3036.
• 22 Beyth RJ, Quinn L, Landefeld CS. A multicomponent intervention to prevent major bleeding complications in older patients receiving warfarin. Ann Intern Med 2000; 133: 687-695.
• 23 MacLean S, Mulla S, Akl EA. et al. Patient values and preferences for decision making in antithrombotic therapy. Chest 2012; 141 (suppl): e1S-e23S.
• 24 Baglin T, Luddington R, Brown K, Baglin C. Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors. Lancet 2003; 362: 523-526.
• 25 Rodger MA, Kahn SR, Wells PS. et al. Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy. CMAJ 2008; 1 79: 417-426.
• 26 Christiansen SC, Cannegieter SC, Koster T. et al. Thrombophilia, clinical factors, and recurrent venous thrombotic events. JAMA 2005; 293: 2352-2361.
• 27 Le Gal G, Kovacs MJ, Carrier M. et al. Risk of recurrent venous thromboembolism after a first oestrogen-associated episode. Thromb Haemost 2010; 104: 498-503.
• 28 Linkins LA, Choi PT, Douketis JD. Clinical Impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism. Ann Intern Med 2003; 139: 893-900.
• 29 Fanikos J, GrassoCorrenti N, Shah R. et al. Major bleeding complications in a specialized anticoagulation service. Am J Cardiol 2005; 96: 595-598.
• 30 Kyrle PA, Eischer L. Predicting the risk of recurrent venous thromboembolism. Hämostaseologie. 2013 33. DOI:10.5482/HAMO-13-03-0018.
• 31 Agnelli G, Buller HR, Cohen A. et al. the AMPLIFY-EXT Investigators. Apixaban for Extended Treatment of Venous Thromboembolism. N Engl J Med 2013; 368: 699-708.
• 32 Schulman S, Kearon C, Kakkar AJ. et al. for the REMEDY and the RE-SONATE Trials Investigators. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med 2013; 368: 709-718.
• 33 Kyrle PA, Minar E, Bialonczyk C. et al. The risk of recurrent venous thromboembolism in men and women. N Engl J Med 2004; 350: 2558-2563.
• 34 Eichinger S, Hron G, Bialonczyk C. et al. Overweight, obesity, and the risk of recurrent venous thromboembolism. Arch Intern Med 2008; 168: 1678-1683.
• 35 Eichinger S, Pecheniuk NM, Hron G. et al. Highdensity lipoprotein and the risk of recurrent venous thromboembolism. Circulation 2007; 115: 1609-1614.
• 36 Becattini C, Agnelli G, Schenone A. et al. WARFASA Investigators. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med 2012; 366: 1959-1967.
• 37 Brighton TA, Eikelboom JW, Mann K. et al. ASPIRE Investigators. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med 2012; 367: 1979-1987.
• 38 Prandoni P, Lensing AW, Piccioli A. et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 2002; 100: 3484-3488.
• 39 Lee AY, Levine MN, Baker RI. et al. Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. N Engl J Med 2003; 349: 146-153.
• 40 Meyer G, Marjanovic Z, Valcke J. et al. Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer. Arch Intern Med 2002; 162: 1729-1735.
• 41 Farge D, Debourdeau P, Beckers M. et al. International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. J Thromb Haemost 2013; 11: 56-70.
• 42 Bates SM, Greer IA, Middeldorp S. et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy. Chest 2012; 141: e691S-e736S.
• 43 Arya R. How I manage venous thromboembolism in pregnancy. Br J Haematol 2011; 153: 698-708.
• 44 Decousus H, Leizorovicz A, Parent F. et al. 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; 338: 409-415.
• 45 Mismetti P, Rivron-Guillot K, Quenet S. et al. A prospective long-term study of 20 patients with a retrievable vena cava filter for secondary prevention of venous thromboembolism. Chest 2007; 131: 223-229.
• 46 White RH, Zhou H, Kim J, Romano PS. A population-based study of the effectiveness of inferior vena cava filter use among patients with venous thromboembolism. Arch Intern Med 2000; 160: 2033-2041.