Low-dose aspirin for preventing recurrent venous thromboembolism

N Engl J Med. 2012 Nov 22;367(21):1979-87. doi: 10.1056/NEJMoa1210384. Epub 2012 Nov 4.


Background: Patients who have had a first episode of unprovoked venous thromboembolism have a high risk of recurrence after anticoagulants are discontinued. Aspirin may be effective in preventing a recurrence of venous thromboembolism.

Methods: We randomly assigned 822 patients who had completed initial anticoagulant therapy after a first episode of unprovoked venous thromboembolism to receive aspirin, at a dose of 100 mg daily, or placebo for up to 4 years. The primary outcome was a recurrence of venous thromboembolism.

Results: During a median follow-up period of 37.2 months, venous thromboembolism recurred in 73 of 411 patients assigned to placebo and in 57 of 411 assigned to aspirin (a rate of 6.5% per year vs. 4.8% per year; hazard ratio with aspirin, 0.74; 95% confidence interval [CI], 0.52 to 1.05; P=0.09). Aspirin reduced the rate of the two prespecified secondary composite outcomes: the rate of venous thromboembolism, myocardial infarction, stroke, or cardiovascular death was reduced by 34% (a rate of 8.0% per year with placebo vs. 5.2% per year with aspirin; hazard ratio with aspirin, 0.66; 95% CI, 0.48 to 0.92; P=0.01), and the rate of venous thromboembolism, myocardial infarction, stroke, major bleeding, or death from any cause was reduced by 33% (hazard ratio, 0.67; 95% CI, 0.49 to 0.91; P=0.01). There was no significant between-group difference in the rates of major or clinically relevant nonmajor bleeding episodes (rate of 0.6% per year with placebo vs. 1.1% per year with aspirin, P=0.22) or serious adverse events.

Conclusions: In this study, aspirin, as compared with placebo, did not significantly reduce the rate of recurrence of venous thromboembolism but resulted in a significant reduction in the rate of major vascular events, with improved net clinical benefit. These results substantiate earlier evidence of a therapeutic benefit of aspirin when it is given to patients after initial anticoagulant therapy for a first episode of unprovoked venous thromboembolism. (Funded by National Health and Medical Research Council [Australia] and others; Australian New Zealand Clinical Trials Registry number, ACTRN12605000004662.).

Publication types

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

MeSH terms

  • Aspirin / administration & dosage*
  • Aspirin / adverse effects
  • Aspirin / therapeutic use
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use
  • Risk
  • Secondary Prevention
  • Venous Thromboembolism / epidemiology
  • Venous Thromboembolism / prevention & control*


  • Platelet Aggregation Inhibitors
  • Aspirin