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Effect of Low-Dose Aspirin on the Occurrence of Venous Thromboembolism: A Randomized Trial

Robert J. Glynn, PhD, ScD; Paul M Ridker, MD; Samuel Z. Goldhaber, MD; and Julie E. Buring, ScD
[+] Article, Author, and Disclosure Information

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

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@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.

Ann Intern Med. 2007;147(8):525-533. doi:10.7326/0003-4819-147-8-200710160-00004
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In this large-scale, long-term trial of initially healthy women, 100 mg of aspirin on alternate days had little association with the overall rate of VTE and the rate of unprovoked VTE. The association of low-dose aspirin with the hazard of VTE was uniform during treatment and did not vary substantially across subgroups. No clear benefit of aspirin was observed among subgroups at particularly high risk for VTE who might benefit most from preventive therapies, although 95% CIs in some subgroups were wide.

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Grahic Jump Location
Figure 1.
Study flow diagram.

WHS = Women's Health Study.

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Grahic Jump Location
Figure 2.
Cumulative incidence of venous thromboembolism (VTE) in the aspirin and placebo groups.

A. Incidence of total VTE (P = 0.58, log-rank test). B. Incidence of unprovoked VTE (P = 0.48, log-rank test) C. Incidence of VTE in women with a history of VTE at baseline (P = 0.33, log-rank test) D. Incidence of VTE in women without a history of VTE at baseline (P = 0.32, log-rank test).

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Grahic Jump Location
Figure 3.
Forest plot showing aspirin effects in subgroups.

BMI = body mass index; HT = hormone therapy; VTE = venous thromboembolism.

Grahic Jump Location




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Treating the Right Clot: Red vs White Thrombi
Posted on November 1, 2007
Akashdeep Singh
Christian Medical College and Hospital Ludhiana,India
Conflict of Interest: None Declared

Aspirin and other antiplatelet drugs are highly effective at reducing major vascular events in patients who are at risk for or who have established atherosclerotic disease.1 Evidence suggests that antiplatelet agents can lower the risk for venous thromboembolism (VTE) in high-risk patients.2 Why aspirin is not effective for primary prevention of VTE in women at low to moderate risk as seen in the present study? Part of the answer to this question may be found in the differences in thrombus formation between the arterial and venous systems. The low-flow and low- pressure venous system is susceptible to reduced blood flow (stasis) and systemic activation of the coagulation cascade, as Virchow described more than 150 years ago, which predisposes to a thrombus even in a nonstenotic vessel. Most venous thrombi consist predominantly of red cells enmeshed in fibrin and contain relatively few platelets; hence, they have been described pathologically as "red thrombi." In contrast, in the high-flow and high-pressure arterial system, thrombi form under the influence of local shear forces, platelet activation, and exposure to thrombogenic substances on damaged vascular surfaces. Arterial thrombi, referred to as "white thrombi," typically are composed predominantly of platelets with relatively little fibrin or red-cell accumulation. Thus, it is plausible to expect that an anticoagulant would be used to prevent venous thromboemboli, whereas an antiplatelet agent would be used to prevent arterial thrombosis.3


1. Antiplatelet Trialists' Collaboration. Collaborative overview of randomised trials of antiplatelet therapy: III. Reduction in venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and medical patients. BMJ 1994; 308:235"“246

2. Pulmonary Embolism Prevention (PEP) Trial Collaborative Group. Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) Trial. Lancet 2000; 355:1295"“1302

3. Richard N. Mitchell : Hemodynamic Disorders, Thromboembolic Disease, and Shock in Robbins and Cotran Pathologic Basis Of Disease 7th Ed. Saunders. 2004 pp119-144

Conflict of Interest:

None declared

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Summary for Patients

Occurrence of Venous Thromboembolism in Women Taking Low-Dose Aspirin

The summary below is from the full report titled “Effect of Low-Dose Aspirin on the Occurrence of Venous Thromboembolism. A Randomized Trial.” It is in the 16 October 2007 issue of Annals of Internal Medicine (volume 147, pages 525-533). The authors are R.J. Glynn, P.M Ridker, S.Z. Goldhaber, and J.E. Buring.


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