Aspirin for the prevention of recurrent venous thromboembolism: the INSPIRE collaboration.

Abstract

BACKGROUND:

In patients with a first unprovoked venous thromboembolism (VTE) the risk of recurrent VTE remains high after anticoagulant treatment is discontinued. The Aspirin for the Prevention of Recurrent Venous Thromboembolism (the Warfarin and Aspirin [WARFASA]) and the Aspirin to Prevent Recurrent Venous Thromboembolism (ASPIRE) trials showed that aspirin reduces this risk, but they were not individually powered to detect treatment effects for particular outcomes or subgroups.

METHODS AND RESULTS:

An individual patient data analysis of these trials was planned, before their results were known, to assess the effect of aspirin versus placebo on recurrent VTE, major vascular events (recurrent VTE, myocardial infarction, stroke, and cardiovascular disease death) and bleeding, overall and within predefined subgroups. The primary analysis, for VTE, was by intention to treat using time-to-event data. Of 1224 patients, 193 had recurrent VTE over 30.4 months' median follow-up. Aspirin reduced recurrent VTE (7.5%/yr versus 5.1%/yr; hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.51-0.90; P=0.008), including both deep-vein thrombosis (HR, 0.66; 95% CI, 0.47-0.92; P=0.01) and pulmonary embolism (HR, 0.66; 95% CI, 0.41-1.06; P=0.08). Aspirin reduced major vascular events (8.7%/yr versus 5.7%/yr; HR, 0.66; 95% CI, 0.50-0.86; P=0.002). The major bleeding rate was low (0.4%/yr for placebo and 0.5%/yr for aspirin). After adjustment for treatment adherence, recurrent VTE was reduced by 42% (HR, 0.58; 95% CI, 0.40-0.85; P=0.005). Prespecified subgroup analyses indicate similar relative, but larger absolute, risk reductions in men and older patients.

CONCLUSIONS:

Aspirin after anticoagulant treatment reduces the overall risk of recurrence by more than a third in a broad cross-section of patients with a first unprovoked VTE, without significantly increasing the risk of bleeding.

CLINICAL TRIAL REGISTRATION URL:

www.anzctr.org.au. Unique identifier: ACTRN12611000684921.

• Authors: John Simes, Cecilia Becattini, Giancarlo Agnelli, John W Eikelboom, Adrienne C Kirby, Rebecca Mister, Paolo Prandoni, Timothy A Brighton, INSPIRE Study Investigators (International Collaboration of Aspirin Trials for Recurrent Venous Thromboembolism)
• Journal: Circulation (Circulation) Vol. 130 Issue 13 Pg. 1062-71 (Sep 23 2014) ISSN: 1524-4539 [Electronic] United States
• PMID: 25156992 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 American Heart Association, Inc.

Chemical References

• Anticoagulants
• Platelet Aggregation Inhibitors
• Warfarin
• Aspirin

Topics

• Adult
• Age Factors
• Aged
• Anticoagulants (therapeutic use)
• Aspirin (therapeutic use)
• Double-Blind Method
• Female
• Follow-Up Studies
• Hemorrhage (epidemiology)
• Humans
• Male
• Middle Aged
• Platelet Aggregation Inhibitors (therapeutic use)
• Recurrence
• Risk Factors
• Sex Factors
• Treatment Outcome
• Venous Thromboembolism (prevention & control)
• Warfarin (therapeutic use)