Aspirin for Preventing the Recurrence of Venous Thromboembolism

Study Questions:

About 20% of patients with unprovoked venous thromboembolism (VTE) have a recurrence within 2 years after the withdrawal of oral anticoagulant therapy. Does use of aspirin prevent recurrent VTE after discontinuation of warfarin?


Aspirin for the Prevention of Recurrent Venous Thromboembolism (Warfarin and Aspirin [WARFASA] study) a multicenter, double-blind, placebo-controlled study, was conducted in patients with first-ever unprovoked VTE who had completed 6-18 months of oral anticoagulant treatment. Patients were randomly assigned to aspirin, 100 mg daily, or placebo for 2 years, with the option of extending the study treatment. The primary efficacy outcome was recurrence of VTE, and major bleeding was the primary safety outcome.


There was no difference between groups for the following: mean age 62 years, >60% male, body mass index, 99% white, index event deep vein thrombosis (DVT) about 60% and pulmonary embolism (PE) 40%, and duration of warfarin treatment (55% 1 year, 35% 6 months). Over a 6-year period, VTE recurred in 28 of the 205 patients who received aspirin and in 43 of the 197 patients who received placebo (6.6% vs. 11.2% per year; hazard ratio, 0.58; 95% confidence interval [CI], 0.36-0.93) (median study period, 24.6 months). During a median treatment period of 23.9 months, 23 patients taking aspirin and 39 taking placebo had a recurrence (5.9% vs. 11.0% per year; hazard ratio, 0.55; 95% CI, 0.33-0.92). One patient in each treatment group had a major bleeding episode. Adverse events were similar in the two groups.


Aspirin reduced the risk of recurrence by about 40% when given to patients with unprovoked VTE who had discontinued anticoagulant treatment, with no apparent increase in the risk of major bleeding.


Extending anticoagulant treatment in unprovoked VTE reduces recurrent rates and is recommended in several guidelines. While other supporting studies are needed, the WARFASA study suggests aspirin therapy is an alternative to extended oral anticoagulant treatment for the long-term secondary prevention of VTE, particularly in persons with increased risk of bleeding and inadequate compliance with warfarin.

Clinical Topics: Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine

Keywords: Risk, Cardiology, Pulmonary Embolism, Venous Thromboembolism, Cardiovascular Diseases, Hemorrhage

< Back to Listings