Aspirin to Prevent Recurrent Thromboembolism

Anticoagulant therapy is commonly recommended for patients who have had an initial episode of unprovoked venous thromboembolism. Once that therapy is discontinued, patients are at high risk for recurrence.

Long-term treatment with a vitamin K antagonist has been shown to be effective in preventing recurrence of venous thromboembolism but not to improve survival. Such treatment is associated with a substantially increased risk of bleeding and is inconvenient for patients, contributing to a high rate of nonadherence to anticoagulant therapy after 3 to 6 months, despite recommendations to prolong the therapy.

Low-dose aspirin is a low cost, simple, and widely available treatment for the primary prevention of venous thromboembolism in surgical patients at high risk. It is possible that aspirin may be used to prevent a recurrence of venous thromboembolism following an initial event.

Researchers recently conducted a study designed to assess the efficacy of low-dose aspirin, compared with placebo, in preventing recurrence of venous thromboembolism in patients who had completed initial anticoagulation with warfarin after a first unprovoked episode of venous thromboembolism. They reported study results online in the New England Journal of Medicine [doi:10.1056/NEJMoa1210384].

The ASPIRE (Aspirin to Prevent Recurrent Venous Thromboembolism) study was a double-blind, randomized, placebo-controlled study. The study randomly assigned 822 patients to receive either a 100-mg daily dose of aspirin (n=411) or placebo (n=411) for up to 4 years. Median study follow-up was 37.2 months

Recurrence of venous thromboembolism was the primary study outcome. Secondary outcomes included major vascular events (a composite of venous thromboembolism, myocardial infarction [MI], stroke, major bleeding, or cardiovascular death) and a measure of the net clinical benefit (a reduction in the rate of the composite of venous thromboembolism, MI, stroke, major bleeding, or death from any cause).

The study was conducted at 56 sites in 5 countries. There were no significant differences in the baseline characteristics in the 2 groups; 54% of the total study population were male, median age was 54 years, 36% had a body mass index of ≥30, 15% said they had a first-degree relative who had had a venous thromboembolism, 5% had a prior provoked venous thromboembolism, and 2% had active cancer.

During the follow-up period, 73 of the 411 patients in the placebo group had a recurrence of venous thromboembolism compared with 57 of 411 in the aspirin group, resulting in a rate of 6.5% versus 4.8% per year (hazard ratio [HR] with aspirin, 0.74; 95% confidence interval [CI], 0.52-1.05; P=.09).

The rate of 2 prespecified secondary composite outcomes was reduced in the aspirin group: the rate of venous thromboembolism, MI, stroke, or cardiovascular death was reduced by 34% (a rate of 8.0% per year with placebo vs 5.2% per year with aspirin; HR with aspirin, 0.66; 95% CI, 0.48-0.92; P=.01). The rate of venous thromboembolism, MI, stroke, or death from any cause was reduced by 33% (rate of 9.0% per year with placebo vs 6.0% per year with aspirin; HR, 0.67; 95% CI, 0.49-0.91; P=.01).

Adverse events leading to hospitalization occurred in 28% (n=117) of patients in the placebo group and 25% (n=102) of patients in the aspirin group, a nonsignificant difference.