Aspirin Safely Prevents Recurrence of Venous Thromboembolism

Lara C. Pullen, PhD

May 25, 2012

May 25, 2012 — Aspirin reduces the risk for recurrence in patients with unprovoked venous thromboembolism who have completed anticoagulant therapy, according to data from a new randomized, placebo-controlled trial. Patients in the trial were able to continue successfully on aspirin with no apparent increase in the risk for major bleeding.

Cecilia Becattini, MD, PhD, from the Division of Internal and Cardiovascular Medicine and Stroke Unit, Department of Internal Medicine, University of Perugia, Italy, and colleagues reported the results of the multicenter, investigator-initiated, double-blind study in the May 24 issue of the New England Journal of Medicine. The study included independent adjudication of outcomes.

Patients receiving oral anticoagulant treatment who were then given aspirin therapy (100 mg daily) had a 42% reduction of recurrence compared with patients given placebo. Venous thromboembolism recurred in 28 of the 205 patients who received aspirin and in 43 of the 197 patients who received placebo (6.6% vs 11.2% per year; hazard ratio, 0.58; 95% confidence interval [CI], 0.36 - 0.93). This reduction is significant and larger than would have been predicted by most vascular experts.

Aspirin was not associated with an increase in the rate of major bleeding compared with placebo (rate, about 0.3% per patient-year in aspirin and placebo groups). The study excluded patients with cancer, clinically significant thrombophilia, or a bleeding event during the period of anticoagulant treatment.

Previous studies have shown that patients with unprovoked venous thromboembolism are at high risk for recurrence after cessation of oral anticoagulant treatment. An earlier meta-analysis, for example, suggested that antiplatelet therapy, predominately with aspirin, could reduce the risk for primary venous thromboembolism in patients at high risk. The current study indicates that aspirin therapy is also effective in preventing recurrence of venous thromboembolism.

Guidelines Stress Need to Balance Recurrence vs Bleeding Risks

In an accompanying editorial, Richard C. Becker, MD, from Duke University Medical Center in Durham, North Carolina, writes, "On the basis of the available evidence, patients with unprovoked venous thromboembolism who are at low-to-moderate risk for bleeding are expected to derive the greatest overall benefit from extending anticoagulant therapy."

Venous thrombi, which encompass both deep-vein thrombi and pulmonary emboli, contain layers of fibrin, platelets, red cells, and leukocytes and usually occur when the patient is stationary, has lowered oxygen tension, and is under oxidative stress. Patients with venous thromboembolism have increased levels of markers of platelet and endothelial activation, which are believed to be involved in the formation of venous thrombi.

Aspirin is 1 of the options for extended treatment for venous thromboembolism. Other treatment options include the oral thrombin inhibitor dabigatran and the oral factor Xa inhibitor rivaroxaban, the study authors explain. Low-intensity warfarin has also been evaluated for the extended treatment of venous thromboembolism and was found, as reported by the study authors, to be associated with a 64% reduction in risk compared with placebo.

The American College of Chest Physicians. describes Dr. Becker, has recently published guidelines highlighting the importance of considering both risk for recurrence at baseline and major bleeding when choosing extended treatments for venous thromboembolism.

The research was supported by the University of Perugia and a grant-in-aid from Bayer HealthCare. Dr. Becattini received an Aventis Fellowship for Clinical Research from the International Society of Thrombosis and Haemostasis. One coauthors reports receiving consulting fees from Bayer HealthCare, Boehringer Ingelheim, and Daiichi Sankyo and lecture fees from Bayer HealthCare, Bristol-Myers Squibb, and sanofi-aventis. One coauthor reports board memberships from Bayer and Boehringer Ingelheim and receiving lecture fees from Bayer, Boehringer Ingelheim, Pfizer, and sanofi-aventis. One coauthor board memberships from Bristol-Myers Squibb, Pfizer, and Bayer Schering Pharma and lecture fees from GlaxoSmithKline, sanofi-aventis, Bayer Schering Pharma, Bristol-Myers Squibb, Pfizer, and Boehringer Ingelheim. No other relevant conflict of interest relevant to this article was reported. Dr. Becker reports consultancy with AstraZeneca, Merck, Boehringer-Ingelheim, and Daiichi-Sankyo.

N Engl J Med. 2012;366:1959-1967. Article extract, Editorial extract


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