Aspirin for preventing the recurrence of venous thromboembolism

N Engl J Med. 2012 May 24;366(21):1959-67. doi: 10.1056/NEJMoa1114238.

Abstract

Background: About 20% of patients with unprovoked venous thromboembolism have a recurrence within 2 years after the withdrawal of oral anticoagulant therapy. Extending anticoagulation prevents recurrences but is associated with increased bleeding. The benefit of aspirin for the prevention of recurrent venous thromboembolism is unknown.

Methods: In this multicenter, investigator-initiated, double-blind study, patients with first-ever unprovoked venous thromboembolism who had completed 6 to 18 months of oral anticoagulant treatment were randomly assigned to aspirin, 100 mg daily, or placebo for 2 years, with the option of extending the study treatment. The primary efficacy outcome was recurrence of venous thromboembolism, and major bleeding was the primary safety outcome.

Results: 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 to 0.93) (median study period, 24.6 months). During a median treatment period of 23.9 months, 23 patients taking aspirin and 39 taking placebo had a recurrence (5.9% vs. 11.0% per year; hazard ratio, 0.55; 95% CI, 0.33 to 0.92). One patient in each treatment group had a major bleeding episode. Adverse events were similar in the two groups.

Conclusions: Aspirin reduced the risk of recurrence when given to patients with unprovoked venous thromboembolism who had discontinued anticoagulant treatment, with no apparent increase in the risk of major bleeding. (Funded by the University of Perugia and others; WARFASA ClinicalTrials.gov number, NCT00222677.).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anticoagulants / therapeutic use
  • Aspirin / adverse effects
  • Aspirin / therapeutic use*
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Hemorrhage / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Pulmonary Embolism / prevention & control
  • Secondary Prevention
  • Venous Thromboembolism / drug therapy
  • Venous Thromboembolism / prevention & control*
  • Venous Thrombosis / prevention & control
  • Vitamin K / antagonists & inhibitors

Substances

  • Anticoagulants
  • Platelet Aggregation Inhibitors
  • Vitamin K
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT00222677