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European Heart Journal Advance Access published online on June 2, 2005
European Heart Journal, doi:10.1093/eurheartj/ehi337
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European Heart Journal © The European Society of Cardiology 2005; All rights reserved
Received November 4, 2004
Revised April 19, 2005
Accepted April 28, 2005

Clinical research

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 Collet 1, Gilles Montalescot 2*, Giancarlo Agnelli 3, Frans van de Werf 4, Enrique P. Gurfinkel 5, Jose López-Sendón 6, Christopher V. Laufenberg 7, Martin Klutman 7, Neelam Gowda 8, Dietrich Gulba 7, and for the GRACE Investigators

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

* To whom correspondence should be addressed.
Gilles Montalescot, E-mail: gilles.montalescot{at}psl.ap-hop-paris.fr


  Abstract

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.

Keywords: Renal dysfunction; Antithrombotic; Bleeding; Mortality.
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