Enoxaparin versus Unfractionated Heparin in Elective Percutaneous Coronary Intervention
Gilles Montalescot, M.D., Ph.D., Harvey D. White, M.B., Ch.B., D.Sc., Richard Gallo, M.D., Marc Cohen, M.D., P. Gabriel Steg, M.D., Philip E.G. Aylward, M.B., Ch.B., Ph.D., Christoph Bode, M.D., Ph.D., Massimo Chiariello, M.D., Spencer B. King, III, M.D., Robert A. Harrington, M.D., Walter J. Desmet, M.D., Carlos Macaya, M.D., Ph.D., Steven R. Steinhubl, M.D., for the STEEPLE Investigators
Background Despite its limitations, unfractionated heparin hasbeen the standard anticoagulant used during percutaneous coronaryintervention (PCI). Several small studies have suggested thatintravenous enoxaparin may be a safe and effective alternative.Our primary aim was to assess the safety of enoxaparin as comparedwith that of unfractionated heparin in elective PCI.
Methods In this prospective, open-label, multicenter, randomizedtrial, we randomly assigned 3528 patients with PCI to receiveenoxaparin (0.5 or 0.75 mg per kilogram of body weight) or unfractionatedheparin adjusted for activated clotting time, stratified accordingto the use or nonuse of glycoprotein IIb/IIIa inhibitors. Theprimary end point was the incidence of major or minor bleedingthat was not related to coronary-artery bypass grafting. Themain secondary end point was the percentage of patients in whomthe target anticoagulation levels were reached.
Results Enoxaparin at a dose of 0.5 mg per kilogram was associatedwith a significant reduction in the rate of non–CABG-relatedbleeding in the first 48 hours, as compared with unfractionatedheparin (5.9% vs. 8.5%; absolute difference, –2.6; 95%confidence interval [CI], –4.7 to –0.6; P=0.01),but the higher enoxaparin dose was not (6.5% vs. 8.5%; absolutedifference, –2.0; 95% CI, –4.0 to 0.0; P=0.051).The incidence of major bleeding was significantly reduced inboth enoxaparin groups, as compared with the unfractionatedheparin group. Target anticoagulation levels were reached insignificantly more patients who received enoxaparin (0.5-mg-per-kilogramdose, 79%; 0.75-mg-per-kilogram dose, 92%) than who receivedunfractionated heparin (20%, P<0.001).
Conclusions In elective PCI, a single intravenous bolus of 0.5mg of enoxaparin per kilogram is associated with reduced ratesof bleeding, and a dose of 0.75 mg per kilogram yields ratessimilar to those for unfractionated heparin, with more predictableanticoagulation levels. The trial was not large enough to providea definitive comparison of efficacy in the prevention of ischemicevents. (ClinicalTrials.gov number, NCT00077844
[ClinicalTrials.gov]
.)
Source Information
From Institut de Cardiologie, Centre Hospitalier Universitaire Pitié–Salpêtrière, Paris (G.M.); the Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand (H.D.W.); the Montreal Heart Institute, Université de Montréal, Montreal (R.G.); the Division of Cardiology, Newark Beth Israel Medical Center, Newark, NJ (M.C.); the Service de Cardiologie, Hôpital Bichat, Paris (P.G.S.); Department of Cardiology, Flinders Medical Center, Adelaide, SA, Australia (P.E.G.A.); Abteilung Innere Medizin III, Universitätsklinikum Freiburg, Freiburg, Germany (C.B.); the Division of Cardiology, Federico 2nd University, Naples, Italy (M.C.); Fuqua Heart Center of Atlanta at Piedmont Hospital, Atlanta (S.B.K.); the Division of Cardiology, Duke University Medical Center, Durham, NC (R.A.H.); University Hospital Gasthuisberg, Leuven, Belgium (W.J.D.); Servicio de Cardiología, Hospital Universitario, Madrid (C.M.); and the Division of Cardiology, University of Kentucky, Lexington (S.R.S.).
Address reprint requests to Dr. Montalescot at Institut de Cardiologie, Bureau 2-236, Centre Hospitalier Universitaire Pitié–Salpêtrière, 47 Boulevard de l'Hôpital, 75013 Paris, France, or at gilles.montalescot{at}psl.aphp.fr.
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