Venous Thromboembolism: How Long to Treat?
Abstract & Commentary
By Harold L. Karpman, MD, FACC, FACP, Clinical Professor of Medicine, UCLA School of Medicine. Dr. Karpman reports no financial relationship to this field of study.
Synopsis: Patients who receive extended anticoagulation are protected from recurrent VTE while receiving long-term therapy. The clinical benefit is maintained after anticoagulation is discontinued, but the magnitude of the benefit is less pronounced.
Source: Ost D, et al. Duration of anticoagulation following venous thromboembolism: a meta-analysis. JAMA. 2005;294: 706-715.
Venous thromboembolism (VTE) continues to be associated with significant morbidity and mortality.1 Despite the proven efficacy of unfractionated or low molecular weight heparin in the treatment of acute VTE, recurrent events are relatively frequent and therefore, chronic anticoagulation with warfarin is usually needed.2-5 However, because of the risk of adverse events (ie, primarily hemorrhage), long-term anticoagulant therapy should be given for as short a period of time as is appropriate. The reason that the optimum duration of long-term anticoagulant therapy is so controversial is because randomized controlled trials and even meta-analyses which have investigated different durations of anticoagulation have reported conflicting results.2-3,6-11
Ost and associates performed a meta-analysis in order to evaluate the published data regarding the ideal duration of anticoagulation which should be recommended for patients with VTE. Sixty-seven articles published between 1969 and 2004 were selected for full review and the results of 15 of these studies were included in the analysis. The median duration of short-term therapy was 1.75 months and long-term therapy was 6.0 months (3.0-10.5 months). The results of this analysis revealed that long-term anticoagulation in patients with VTE reduces the risk of recurrence and that the magnitude of risk reduction was greatest when patients were receiving treatment however, even if treatment was stopped, measurable benefit continued to be present.
Commentary
The optimal duration of anticoagulant therapy for VTE is that time which balances the positive benefit of anticoagulation in preventing recurrent VTE against minimizing major bleeding episodes. The meta-analysis findings reported by Ost were consistent with previously published analyses10 which demonstrated that long-term anticoagulation effectively reduces the risk of recurrent VTE and that the incremental benefit of anticoagulant therapy is strongly present for at least 6 months after VTE occurrence. The magnitude of risk reduction is greatest while treatment is being administered, but, even if treatment is stopped, significant benefit remains present. The incremental benefit of prolonging anticoagulation decreases as the duration of anticoagulation increases but persists for at least the initial 6 months.
In summary, it would appear that the prudent physician must focus on individual patient risk stratification which suggests that lifelong anticoagulation may be needed in certain high-risk patients while low-risk populations may be subjected to a shorter period of anticoagulation in order to avoid major bleeding episodes, albeit that the bleeding risk due to anticoagulation is very low both in absolute and relative terms. It should also be recognized that patients who receive extended anticoagulation are largely protected from recurrent VTE and, although the clinical benefit is maintained after anticoagulation is discontinued, the magnitude of the benefit is less pronounced. Finally, based on the limited available evidence, it appears that 6 or more months of treatment for patients at higher risk may be warranted; and it should be recognized that increasing the duration of anticoagulation beyond 6-months results in additional relatively modest incremental risk reduction.
References
1. Goldhaber SZ, et al. Acute pulmonary embolism: clinical outcomes in the international cooperative pulmonary embolism registry (ICOPER). Lancet. 1999;353:1386-1389.
2. Agnelli G, et al. Extended oral anticoagulant therapy after a first episode of pulmonary embolism. Ann Intern Med. 2003;139:19-25.
3. Agnelli G, et al. 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;345:165-169.
4. British Thoracic Society Standards of Care Committee Pulmonary Embolism Guideline Development Group. British Thoracic Society guidelines for the management of suspected acute pulmonary embolism. Thorax. 2003;58:470-483.
5. Buller HR, et al. Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3 Suppl):401S-428S; Erratum in: Chest. 2005;127:416.
6. Pinede L, et al. 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.
7. Kearon C, et al. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl of Med. 2003;349:631-639.
8. Schulman S, et al. Secondary prevention of venous thromboembolism with the oral direct thrombin inhibitor ximelagatran. N Engl J Med. 2003;349: 1713-1721.
9. Schulman S, et al. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. Duration of Anticoagulation Trial Study Group. N Engl J Med. 1995;3302:1661-1665.
10. Pinede L, et al. Comparison of long versus short duration of anticoagulant therapy after a first episode of venous thromboembolism: a meta-analysis of randomized, controlled trials. J Intern Med. 2000;247:553-562.
11. Fennerty A, et al. Anticoagulants in venous thromboembolism. BMJ. 1988;297:1285-1288.
Patients who receive extended anticoagulation are protected from recurrent VTE while receiving long-term therapy. The clinical benefit is maintained after anticoagulation is discontinued, but the magnitude of the benefit is less pronounced.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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