Effect of Low-Dose Aspirin on the Occurrence of Venous Thromboembolism

Effect of Low-Dose Aspirin on the Occurrence of Venous Thromboembolism

A Randomized Trial

From Brigham and Women's Hospital, Harvard Medical School, and Harvard School of Public Health, Boston, Massachusetts.

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.

Article and Author Information

Acknowledgments: The authors are indebted to the 39 876 participants in the Women's Health Study for their dedicated and conscientious collaboration and to the entire staff of the study. They also thank Roche Molecular Systems for providing the genotyping platform used in the study.
Grant Support: By the National Institutes of Health (grants HL71221, HL43851, and CA47988). Natural Source Vitamin E Association provided the vitamin E and vitamin E placebo, and Bayer HealthCare provided the aspirin and placebo aspirin.
Potential Financial Conflicts of Interest: Grants received: R.J. Glynn (Bristol-Myers Squibb). Honoraria: J.E. Buring (Bayer HealthCare). Other: J.E. Buring (Bayer HealthCare, Natural Source Vitamin E Association).
Requests for Single Reprints: Robert J. Glynn, PhD, ScD, Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue, Boston, MA 02215; e-mail, rglynn{at}rics.bwh.harvard.edu.
Current Author Addresses: Drs. Glynn, Ridker, and Buring: Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue, Boston, MA 02215.
Dr. Goldhaber: Division of Cardiology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115.
Author Contributions: Conception and design: R.J. Glynn, P.M. Ridker, J.E. Buring.
Analysis and interpretation of the data: R.J. Glynn, P.M. Ridker, S.Z. Goldhaber, J.E. Buring.
Drafting of the article: R.J. Glynn.
Critical revision of the article for important intellectual content: R.J. Glynn, P.M. Ridker, S.Z. Goldhaber, J.E. Buring.
Final approval of the article: R.J. Glynn, P.M. Ridker, S.Z. Goldhaber, J.E. Buring.
Provision of study materials or patients: J.E. Buring.
Statistical expertise: R.J. Glynn.
Obtaining of funding: R.J. Glynn, J.E. Buring.
Collection and assembly of data: R.J. Glynn, P.M. Ridker, J.E. Buring.