Aspirin for the Prevention of Recurrent Venous Thromboembolism (Warfarin and Aspirin) - WARFASA
The goal of the trial was to evaluate treatment with aspirin compared with placebo among patients with treated venous thromboembolism.
Aspirin will prevent recurrent venous thromboembolism.
- Placebo Controlled
- Patients at least 18 years of age who had been treated for 6-18 months with oral anticoagulant therapy for an unprovoked venous thromboembolism
- Venous thromboembolism was defined as proximal deep vein thrombosis, pulmonary embolism, or both
Number of enrollees: 403
Duration of follow-up: Median 25 months
Mean patient age: 62 years
Percentage female: 34%
- Bleeding during anticoagulation therapy
- Recurrent venous thromboembolism
- Major bleeding
- Nonfatal myocardial infarction
- Unstable angina
- Stroke/transient ischemic attack
- Acute limb ischemia
- Death from any cause
Patients with venous thromboembolism who had been treated with oral anticoagulant therapy for 6-18 months were randomized to aspirin 100 mg daily (n = 205) versus placebo (n = 198) for 2 years.
Overall, 403 patients were randomized. The mean age was 62 years, 34% were women, mean body mass index was 27 kg/m2, index event: deep vein thrombosis in 60% and pulmonary embolus in 40%, and prior duration of anticoagulation: 6 months in 37%, 12 months in 54%, and 18 months in the remainder.
Over a median follow-up of 25 months, the primary efficacy outcome, recurrent venous thromboembolism occurred in 6.6% per year in the aspirin group versus 11.2% per year in the placebo group (p = 0.02). Among patients who entered the trial with a pulmonary embolus, recurrences were 6.7% versus 13.5% (p = 0.02) and among patients who entered the trial with a deep vein thrombosis, recurrences were 6.5% versus 10.2% (p = 0.17), respectively, for aspirin versus placebo. Predictors for recurrence were age >65 years and male gender. A relatively short duration of anticoagulation (6 months) was not a predictor.
Major bleeding events: 1 versus 1, and clinically relevant nonmajor bleeding events: 3 versus 3, respectively.
Deaths: 6 versus 5, and arterial events: 8 versus 5, respectively.
Among patients who completed a course of anticoagulation for an unprovoked venous thromboembolism and without a primary indication for antiplatelet therapy, the use of low-dose aspirin reduced recurrent venous thromboembolic events compared with placebo. This was achieved without an increase in major bleeding events, which may have been due to exclusion of patients who were at elevated risk for bleeding. Extending the duration of anticoagulation therapy is also effective; however, this strategy is associated with a higher risk of bleeding. Low-dose aspirin represents an option in the long-term management of patients with prior venous thromboembolism.
Becattini C, Agnelli G, Schenone A, et al., on behalf of the WARFASA Investigators. Aspirin for Preventing the Recurrence of Venous Thromboembolism. N Engl J Med 2012;366:1959-67.
Clinical Topics: Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine
Keywords: Recurrence, Follow-Up Studies, Body Mass Index, Pulmonary Embolism, Venous Thromboembolism, Venous Thrombosis, Hemorrhage
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