title: Low-dose aspirin for preventing recurrent venous thromboembolism.
abstract: 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.).
authors.affiliation: Department of Haematology, South Eastern Area Laboratory Services (SEALS), Prince of Wales Hospital, Sydney, Australia. aspire@ctc.usyd.edu.au
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Brighton
authors.forename: John W
authors.initials: JW
authors.lastname: Eikelboom
authors.forename: Kristy
authors.initials: K
authors.lastname: Mann
authors.forename: Rebecca
authors.initials: R
authors.lastname: Mister
authors.forename: Alexander
authors.initials: A
authors.lastname: Gallus
authors.forename: Paul
authors.initials: P
authors.lastname: Ockelford
authors.forename: Harry
authors.initials: H
authors.lastname: Gibbs
authors.forename: Wendy
authors.initials: W
authors.lastname: Hague
authors.forename: Denis
authors.initials: D
authors.lastname: Xavier
authors.forename: Rafael
authors.initials: R
authors.lastname: Diaz
authors.forename: Adrienne
authors.initials: A
authors.lastname: Kirby
authors.forename: John
authors.initials: J
authors.lastname: Simes
mesh_terms: D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D012306:Risk; D055502:Secondary Prevention; D054556:Venous Thromboembolism / Q000453:epidemiology / Q000517:prevention & control*
chemical_list: D010975:Platelet Aggregation Inhibitors; D001241:Aspirin