Effect of low-dose aspirin on the occurrence of venous thromboembolism: a randomized trial

Abstract

Background: Short-term aspirin therapy can lower the risk for venous thromboembolism (VTE) in high-risk patients, but whether the long-term use of low-dose aspirin reduces risk in healthy adults is uncertain.

Objective: To test the efficacy of long-term aspirin therapy for preventing VTE.

Design: Secondary analysis of a 10-year randomized, double-blind, placebo-controlled trial.

Setting: U.S. female health care professionals in the Women's Health Study.

Participants: 39,876 initially healthy women age 45 years or older (26,779 gave blood samples that were evaluated for factor V Leiden, G20210A prothrombin, and MTHFR 677C>T polymorphisms).

Measurements: Documented VTE (deep venous thrombosis or pulmonary embolism) and unprovoked VTE (no recent surgery, trauma, or cancer diagnosis) were prospectively evaluated, secondary end points.

Intervention: Aspirin, 100 mg, or placebo on alternate days.

Results: Venous thromboembolism occurred in 482 women during follow-up, an incidence higher than that of myocardial infarction and nearly equal to that of stroke. The incidence of VTE (per 1000 person-years) was 1.18 among women randomly assigned to active aspirin, compared with 1.25 among women randomly assigned to placebo (relative hazard, 0.95 [95% CI, 0.79 to 1.13]; rate difference, -0.06 [CI, -0.28 to 0.16]). For unprovoked VTE, the relative hazard was 0.90 (CI, 0.70 to 1.16) and the rate difference was -0.06 (CI, -0.21 to 0.10). Relative hazards associated with aspirin use in higher-risk subgroups were 0.83 (CI, 0.50 to 1.39) among women with either factor V Leiden or the prothrombin mutation and 1.36 (CI, 0.77 to 2.41) among those with a history of VTE.

Limitation: Venous thromboembolism was a secondary end point in the Women's Health Study.

Conclusion: These data suggest that long-term, low-dose aspirin treatment has little effect on the prevention of VTE in initially healthy women. ClinicalTrials.gov registration number: NCT00000479.