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Eric L. Eisenstein, DBA; Kevin J. Anstrom, PhD; David F. Kong, MD; Linda K. Shaw, MS; Robert H. Tuttle, MSPH; Daniel B. Mark, MD, MPH; Judith M. Kramer, MD, MS; Robert A. Harrington, MD; David B. Matchar, MD; David E. Kandzari, MD; Eric D. Peterson, MD, MPH; Kevin A. Schulman, MD; Robert M. Califf, MD

JAMA. 2007;297:159-168. Published online December 5, 2006 (doi:10.1001/jama.297.2.joc60179)

Context  Recent studies of drug-eluting intracoronary stents suggest that current antiplatelet regimens may not be sufficient to prevent late stent thrombosis.

Objective  To assess the association between clopidogrel use and long-term clinical outcomes of patients receiving drug-eluting stents (DES) and bare-metal stents (BMS) for treatment of coronary artery disease.

Design, Setting, and Patients  An observational study examining consecutive patients receiving intracoronary stents at Duke Heart Center, a tertiary care medical center in Durham, NC, between January 1, 2000, and July 31, 2005, with follow-up contact at 6, 12, and 24 months through September 7, 2006. Study population included 4666 patients undergoing initial percutaneous coronary intervention with BMS (n = 3165) or DES (n = 1501). Landmark analyses were performed among patients who were event-free (no death, myocardial infarction [MI], or revascularization) at 6- and 12-month follow-up. At these points, patients were divided into 4 groups based on stent type and self-reported clopidogrel use: DES with clopidogrel, DES without clopidogrel, BMS with clopidogrel, and BMS without clopidogrel.

Main Outcome Measures  Death, nonfatal MI, and the composite of death or MI at 24-month follow-up.

Results  Among patients with DES who were event-free at 6 months (637 with and 579 without clopidogrel), clopidogrel use was a significant predictor of lower adjusted rates of death (2.0% with vs 5.3% without; difference, –3.3%; 95% CI, –6.3% to –0.3%; P = .03) and death or MI (3.1% vs 7.2%; difference, –4.1%; 95% CI, –7.6% to –0.6%; P = .02) at 24 months. However, among patients with BMS (417 with and 1976 without clopidogrel), there were no differences in death (3.7% vs 4.5%; difference, –0.7%; 95% CI, –2.9% to 1.4%; P = .50) and death or MI (5.5% vs 6.0%; difference, –0.5%; 95% CI, –3.2% to 2.2%; P = .70). Among patients with DES who were event-free at 12 months (252 with and 276 without clopidogrel), clopidogrel use continued to predict lower rates of death (0% vs 3.5%; difference, –3.5%; 95% CI, –5.9% to –1.1%; P = .004) and death or MI (0% vs 4.5%; difference, –4.5%; 95% CI, –7.1% to –1.9%; P<.001) at 24 months. However, among patients with BMS (346 with and 1644 without clopidogrel), there continued to be no differences in death (3.3% vs 2.7%; difference, 0.6%; 95% CI, –1.5% to 2.8%; P = .57) and death or MI (4.7% vs 3.6%; difference, 1.0%; 95% CI, –1.6% to 3.6%; P = .44).

Conclusions  The extended use of clopidogrel in patients with DES may be associated with a reduced risk for death and death or MI. However, the appropriate duration for clopidogrel administration can only be determined within the context of a large-scale randomized clinical trial.

Author Affiliations: Departments of Medicine (Drs Eisenstein, Kong, Mark, Kramer, Harrington, Matchar, Kandzari, Peterson, Schulman, and Califf) and Biostatistics and Bioinformatics (Dr Anstrom), Duke University Medical Center; Duke Clinical Research Institute (Drs Eisenstein, Anstrom, Kong, Mark, Kramer, Harrington, Kandzari, Peterson, Schulman, and Ms Shaw and Mr Tuttle); Duke Translational Medicine Institute (Drs Eisenstein, Anstrom, Kong, Mark, Kramer, Harrington, Matchar, Kandzari, Peterson, Schulman, Califf, and Ms Shaw and Mr Tuttle); and the Duke Center for Clinical Health Policy Research (Dr Matchar), Durham, NC.

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