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European Heart Journal Advance Access originally published online on February 16, 2005
European Heart Journal 2005 26(11):1063-1069; doi:10.1093/eurheartj/ehi139
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© The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: journals.permissions@oupjournals.org

Impact of combined pharmacologic treatment with clopidogrel and a statin on outcomes of patients with non-ST-segment elevation acute coronary syndromes: perspectives from a large multinational registry

Michael J. Lim1, Frederick A. Spencer2, Joel M. Gore2, Omar H. Dabbous3, Giancarlo Agnelli4, Eva M. Kline-Rogers5, Donna DiBenedetto2, Kim A. Eagle5, Rajendra H. Mehta6,* for the GRACE Investigators

1Division of Cardiology, School of Medicine, Saint Louis University, St Louis, MO, USA
2Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, MA, USA
3Center for Outcomes Research, University of Massachusetts Medical School, Worcester, MA, USA
4University of Perugia, Ospedale Silvestrini, Perugia, Italy
5Division of Cardiology, The University of Michigan Cardiovascular Center, Ann Arbor, MI, USA
6Duke Clinical Research Institute, Durham, NC, USA

Received 10 July 2004; revised 15 December 2004; accepted 5 January 2005; online publish-ahead-of-print 16 February 2005.

* Corresponding author: 2802 Leslie Park Circle, Ann Arbor, MI 48105, USA. Tel: +1 734 668 7192; fax: +1 734 668 7192. E-mail address: mehta007{at}dcri.duke.edu

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

Aims To evaluate clinical outcomes associated with the combined use of clopidogrel and statins vs. clopidogrel alone on a background of aspirin therapy in patients with the spectrum of acute coronary syndromes (ACS).

Methods and results Utilizing data from the Global Registry of Acute Coronary Events, we studied 15 693 patients admitted with non-ST-segment elevation myocardial infarction (MI) or unstable angina, dividing them according to discharge medications: aspirin alone (group I); aspirin + clopidogrel (group II); aspirin + statin (group III); aspirin + clopidogrel + statin (group IV). Among the groups of patients in whom clopidogrel was used (groups II and IV), group II patients were older, more likely to have prior MI, but less likely to have a history of prior revascularization. In-hospital cardiac catheterization and revascularization rates were similar between groups II and IV. Importantly, Kaplan–Meier analysis showed that the 6 month mortality rate was lower in group IV (log-rank test 22.8, P<0.0001). The hazard ratio for the 6 month mortality rate was adjusted using the Cox proportional hazard model for confounding variables and for propensity score, and the 6 month mortality rate for patients in group IV remained lower compared with those in group II [0.59 (0.41–0.86), P<0.0001].

Conclusion Our data suggest that the combination of clopidogrel with a statin has synergistic effects on the clinical outcomes of patients with non-ST-segment elevation ACS.

Key Words: Acute coronary syndrome • Clopidogrel • Statin • Non-ST-segment elevation


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