PREVENTION OF PULMONARY EMBOLISM AND DEEP VEIN THROMBOSIS WITH LOW DOSE ASPIRIN: THE PULMONARY EMBOLISM PREVENTION (PEP) TRIAL

Abstract

The Pulmonary Embolism Prevention (PEP) Trial was designed to assess the effects of a 35 day course of aspirin (160 mg daily) on the risks of thromboembolic events, other cardiovascular outcomes and bleeding among individuals undergoing surgery for hip fracture or joint replacement. From 1992 to 1998, 148 hospitals in Australia, New Zealand, South Africa, Sweden and the United Kingdom randomised 13,356 hip fracture patients, and 22 hospitals in New Zealand randomised 4,088 elective arthroplasty patients. Among hip fracture patients, aspirin produced proportional reductions in PE of 43% (95% confidence interval [CI] 18% to 60%; 2P=0.002) and symptomatic DVT of 29% (95% CI 3% to 48%; 2P=0.03). PE or DVT was confirmed in 105 (1.6%) of 6679 patients allocated aspirin versus 165 (2.5%) of 6677 allocated placebo, representing an absolute reduction of 9±2 per 1000 and a proportional reduction of 36% (95% CI 19% to 50%; 2P=0.0003). Aspirin prevented 4±1 fatal pulmonary emboli per 1000 treated (18 aspirin vs 43 placebo deaths), representing a proportional reduction of 58% (95% CI 27% to 76%; 2P=0.002), with no apparent effect on deaths from other vascular (hazard ratio 1.04; 95% CI 0.86 to 1.26) or non-vascular cause (1.01; 95% CI 0.84 to 1.23). Deaths due to bleeding were rare (13 aspirin vs 15 placebo), but there was an excess of 6±3 post-operative transfused bleeds per 1000 allocated aspirin (2P=0.04). Among elective arthroplasty patients, venous thromboembolism rates were lower but the proportional effects of aspirin appeared similar to those among hip fracture patients.