Clopidogrel Use and Long-term Clinical Outcomes After Drug-Eluting Stent Implantation
- 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
- 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.
- Corresponding Author: Eric L. Eisenstein, DBA, Duke Clinical Research Institute, Duke University Medical Center, Box 3865, 2400 Pratt St, Room 0311, Durham, NC 27710 (eric.eisenstein{at}duke.edu).
Abstract
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.
Published online December 5, 2006 (doi:10.1001/jama.297.2.joc60179).
