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European Heart Journal Advance Access originally published online on June 2, 2005
European Heart Journal 2005 26(21):2285-2293; doi:10.1093/eurheartj/ehi337
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© The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Non-ST-segment elevation acute coronary syndrome in patients with renal dysfunction: benefit of low-molecular-weight heparin alone or with glycoprotein IIb/IIIa inhibitors on outcomes. The Global Registry of Acute Coronary Events

Jean-Philippe Collet1, Gilles Montalescot1,*, Giancarlo Agnelli2, Frans Van de Werf3, Enrique P. Gurfinkel4, Jose López-Sendón5, Christopher V. Laufenberg6, Martin Klutman6, Neelam Gowda7, Dietrich Gulba6 for the GRACE Investigators

1Department of Cardiology, Centre Hôpital Pitié-Salpêtrière, Bureau 2-236, 47, Boulevard de l'Hôpital, 75013 Paris, France
2Department of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy
3Department of Cardiology, Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium
4Department of Cardiology, ICYCC Favaloro Foundation, Buenos Aires, Argentina
5Department of Cardiology, Hospital Universitario Gregorio Marañon, Madrid, Spain
6Department of Cardiology, Krankenhaus Düren, Düren, NRW, Germany
7University of Massachusetts Medical School, Worcester, MA, USA

Received 4 November 2004; revised 19 April 2005; accepted 28 April 2005; online publish-ahead-of-print 2 June 2005.

* Corresponding author: Tel: +33 1 42 16 30 06; fax: +33 1 42 16 29 31. E-mail address: gilles.montalescot{at}psl.ap-hop-paris.fr

This paper was guest edited by Prof. Bernard J. Gersh, Mayo Clinic, Rochester, USA

Aims To determine whether low-molecular-weight heparin (LMWH)+glycoprotein (GP) IIb/IIIa inhibitors provide greater benefit than unfractionated heparin (UFH)+GP IIb/IIIa inhibitors, irrespective of renal status.

Methods and results Patients in the Global Registry of Acute Coronary Events (GRACE) were divided into three groups according to creatinine clearance (CrCl): normal renal function (CrCl >60 mL/min), moderate renal dysfunction (30<CrCl≤60 mL/min), and severe (CrCl≤30 mL/min) renal dysfunction. Data were analysed from 11 881 patients with acute coronary syndrome (ACS). Patients with moderate (n=3705) or severe (n=982) renal dysfunction were at higher risk of adverse outcomes than those with normal renal function. Decreasing CrCl was an independent predictor of mortality at 30 days and in-hospital major bleeding. LMWH+GP IIb/IIIa inhibitors were used significantly less frequently in patients with severe (2.0%) or moderate (3.1%) renal dysfunction than in those with normal function (3.9%, P=0.0056). LMWH alone was more beneficial than UFH alone, irrespective of renal status. LMWH alone was an independent predictor of 30 day survival [odds ratio (OR) 0.56; 95% confidence interval (CI) 0.43–0.73] and lower risk of in-hospital bleeding (OR 0.66; 95% CI 0.48–0.92). Bleeding rates were significantly lower with LMWH+GP IIb/IIIa inhibitors than those with UFH+GP IIb/IIIa inhibitors. Use of UFH+GP IIb/IIIa inhibitors was an independent predictor of bleeding (OR 2.02; 95% CI 1.42–2.90) compared with UFH alone.

Conclusion In patients with renal dysfunction and non-ST-segment elevation ACS, bleeding complications are more frequent and outcomes appear worse in individuals treated with UFH compared with LMWH. Combination therapy with LMWH and GP IIb/IIIa inhibitors appears to be better tolerated than with UFH and GP IIb/IIIa inhibitors.

Key Words: Renal dysfunction • Antithrombotic • Bleeding • Mortality


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