Aspirin for the Prevention of Recurrent Venous Thromboembolism (Warfarin and Aspirin) - WARFASA

May 23, 2012
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
University of Perugia, Bayer Healthcare, and Aventis
Date Published:
01/01/2012
Date Updated:
05/23/2012
Original Posted Date:
05/23/2012
References

Description:

The goal of the trial was to evaluate treatment with aspirin compared with placebo among patients with treated venous thromboembolism.

Hypothesis:

Aspirin will prevent recurrent venous thromboembolism.

Study Design

  • Placebo Controlled
  • Blinded
  • Randomized
  • Parallel

Patient Populations:

  • 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%

Exclusions:

  • Cancer
  • Thrombophilia
  • Bleeding during anticoagulation therapy

Primary Endpoints:

  • Recurrent venous thromboembolism
  • Major bleeding

Secondary Endpoints:

  • Nonfatal myocardial infarction
  • Unstable angina
  • Stroke/transient ischemic attack
  • Acute limb ischemia
  • Death from any cause

Drug/Procedures Used:

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.

Principal Findings:

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.

Interpretation:

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.

References:

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.

Keywords: Recurrence, Follow-Up Studies, Body Mass Index, Pulmonary Embolism, Venous Thromboembolism, Venous Thrombosis, Hemorrhage


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