Background: Venous thromboembolism (VTE) is a problem that often occurs in adults without known risk factors (e.g., surgery, trauma, immobilization, cancer). Previous studies have shown that short-term aspirin therapy reduces the risk of VTE in high-risk patients; however, there is limited and conflicting evidence that aspirin use reduces VTE incidence in patients at average risk. Glynn and colleagues examined the effectiveness of aspirin at preventing VTE in a large group of initially healthy women enrolled in the Women's Health Study.

The Study: This was a secondary analysis of the Women's Health Study, a randomized, double-blind, placebo-controlled trial of low-dose aspirin for the prevention of cardiovascular events in 39,876 initially healthy women. Invitations were mailed to 1.7 million U.S. female health professionals. Those who returned baseline questionnaires and met all eligibility criteria were enrolled in a three-month placebo run-in phase to identify participants most likely to adhere to treatment. Eligible participants were 45 years or older; had no history of cardiovascular disease, cancer, or other major chronic diseases; and did not use aspirin or anticoagulants. Women who reported a history of deep venous thrombosis or pulmonary embolism were noted, but not excluded from the trial.

The final study population was randomly assigned, by age-stratified groups, to take 100 mg of aspirin or an indistinguishable placebo every other day. Participants completed follow-up questionnaires every six months for the duration of the trial; questions included information on adherence to study drugs, adverse effects, and the occurrence of VTE. An independent, blinded end-points committee determined causes of death. After 10 years, 67 percent of women reported that they were still taking at least two thirds of their aspirin or placebo tablets. An average of 12 percent of women in both groups also reported using over-the-counter aspirin for four or more days per month.

Results: During the study, 482 women had a confirmed VTE, 241 of whom were classified as having an unprovoked event (i.e., occurring in the absence of an identifiable risk factor). By comparison, 487 women had a first stroke and 391 women had a first myo-cardial infarction. There was no statistically significant difference between the aspirin and placebo groups in overall VTE incidence (relative risk [RR] = 0.95; 95% confidence interval [CI], 0.79 to 1.13) or unprovoked VTE (RR = 0.90; 95% CI, 0.70 to 1.16). Women with factor V Leiden or a prothrombin mutation had nearly three times the risk of VTE than the study population, but this risk was not reduced in those taking aspirin. Analyses restricted to women who reported taking at least two thirds of the study drugs also did not show a protective effect of aspirin. However, women who took aspirin were more likely to develop ulcers and have clinically significant bleeding.

Conclusion: The authors conclude that long-term use of low-dose aspirin is ineffective at preventing VTE in healthy adult women. Women who choose aspirin therapy for other reasons, such as primary or secondary prevention of cardiovascular events, should be made aware that such therapy will not protect them against future VTE.