PEP trial

Abstract

The Pulmonary Embolism Prevention (PEP) trial1Pulmonary Embolism Prevention (PEP) Trial Collaborative GroupPrevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial.Lancet. 2000; 355: 1295-1302Summary Full Text Full Text PDF PubMed Scopus (940) Google Scholar demonstrates the efficacy of aspirin in reducing the risk of pulmonary embolism (PE) and symptomatic deep venous thrombosis (DVT) in patients undergoing surgery for hip fracture up to day 35. The clinical evaluation was by mortality and in-hospital morbidity (DVT, PE, myocardial infarction, stroke, and bleeding) instead of the radiographic criterion of phlebography for DVT that is most often used.2Eriksson BI Wille-Jorgensen P Kälebo P et al.A comparison of recombinant hirudin with a low-molecular-weight heparin to prevent thromboembolic complications after total hip replacement.N Engl J Med. 1997; 337: 1329-1335Crossref PubMed Scopus (424) Google Scholar The efficacy of aspirin was observed in patients undergoing surgery for hip fracture and it is very surprising that the PEP group makes recommendations for a much larger population of high-risk medical patients. The thromboembolism risk in medical patients was estimated in the 1994 meta-analysis on only 555 patients, and there were very different illnesses and variable doses of aspirin.3Antiplatelet Trialist's CollaborationCollaborative overview of randomised trials of antiplatelet therapy-III: reduction of venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and medical patients.BMJ. 1994; 308: 235-246Crossref PubMed Scopus (32) Google Scholar, 4Collins R Baigent C Sandercock P Peto R For the Antiplatelet Trialist's Collaboration. Antiplatelet therapy for thromboprophylaxis: the need for careful consideration of the evidence from randomised trials.BMJ. 1994; 309: 1215-1217Crossref PubMed Scopus (73) Google Scholar The routine use of aspirin for DVT prevention in medical patients has never been evaluated prospectively, and its efficacy cannot be extrapolated from a trial in hip-surgery fracture and a meta-analysis of trials in patients as diverse as orthopaedic surgical, general surgical, and high-risk medical. Subgroup data in the PEP trial show that concomitant use of aspirin and low-molecular-weight heparin (LMWH) did not produce any additional reduction in risk of DVT (event rate 1·4% for aspirin plus LMWH and 1·8% for LMWH alone; p=0·37). Indeed the thrombosis risk seems similar for aspirin alone (1·7%), for unfractionated heparin plus aspirin (1·6%), and for LMWH alone (1·8%). Given the widespread use of LMWH thromboprophylaxis in Europe in orthopaedic patients and the lack of synergy of LMWH and aspirin in the PEP trial, the place of aspirin when LMWH therapy is used can be questioned. Moreover, the risk of bleeding may be increased by this combination. In PEP the excess of bleeds requiring transfusion among patients on both heparin and aspirin was not significant (p=0·06). However, aspirin was associated with a 12 per 1000 excess among patients also receiving subcutaneous heparin (3·4% vs 2·3%) but only a one per 1000 excess among those not on heparin (2·6% vs 2·5%). Despite the PEP trial, aspirin is not clearly useful in orthopaedic patients receiving LMWH. In general surgical and medical patients, further studies are needed comparing the preventive effect of LMWH and aspirin. PEP trialAuthors' reply Full-Text PDF