Aspirin for the Prevention of Recurrent Venous Thromboembolism: The INSPIRE Collaboration
Background—In patients with a first unprovoked venous thromboembolism (VTE) the risk of recurrent VTE remains high after anticoagulant treatment is discontinued. The WARFASA and 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, MI, stroke and CVD 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%/year vs 5.1%/year; hazard ratio (HR), 0.68; 95% 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%/year vs 5.7%/year; HR, 0.66; 95% CI, 0.50-0.86; P=0.002). The major bleeding rate was low (0.4%/year for placebo and 0.5%/year 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 Information—National Health and Medical Research Council (Australia) (ACTRN12611000684921 at www.anzctr.org.au).
- Received January 19, 2014.
- Revision received July 4, 2014.
- Accepted July 7, 2014.