About 20% of patients with unprovoked venous thromboembolism experience recurrence within 2 years of discontinuing normal treatment with vitamin K antagonists. One potential solution would be to extend vitamin K antagonist therapy. However, this strategy is associated with an increased risk of bleeding as well as the inconvenience of INR monitoring. The WARFASA investigators, therefore, set out to determine the efficacy and safety of using aspirin (100 mg daily) after 6–18 months of treatment with vitamin K antagonists in a multicenter, randomized trial of patients who had experienced a first-ever, unprovoked venous thromboembolism.

In total, 205 patients received aspirin and 197 patients received placebo (median treatment duration 23.9 months; median study period 24.6 months). Venous thromboembolism recurred in 28 and 43 individuals assigned to aspirin or placebo, respectively (6.6% vs 11.2% per year; HR 0.58, 95% CI 0.36–0.93, P=0.02). The benefit of aspirin seemed to be driven largely by a reduced risk of deep-vein thrombosis (16 vs 28 events; HR 0.51, 95% CI 0.27–0.94, P=0.03) rather than a change in the risk of pulmonary embolism (11 vs 14 events; HR 0.70, 95% CI 0.32–1.54, P=0.37).

Notably, no differences were observed between the aspirin and placebo groups, respectively, for occurrence of nonfatal major bleeding or clinically relevant, nonmajor bleeding (4 per group; HR 0.98, 95% CI 0.24–3.96, P=0.97), death (6 vs 5; HR 1.04, 95% CI 0.32–3.42, P=0.95), or arterial events (8 vs 5; HR 1.43, 95% CI 0.47–4.37, P=0.53). In their report published in the New England Journal of Medicine, the investigators conclude that “aspirin therapy is a potential alternative to extended oral anticoagulation treatment for the long-term secondary prevention of venous thromboembolism”.