Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation.
BACKGROUND
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.


METHODS
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.


METHODS
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.
Eisenstein
Eric L
EL
Department of Medicine, Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27710, USA. eric.eisenstein@duke.edu
Anstrom
Kevin J
KJ
Kong
David F
DF
Shaw
Linda K
LK
Tuttle
Robert H
RH
Mark
Daniel B
DB
Kramer
Judith M
JM
Harrington
Robert A
RA
Matchar
David B
DB
Kandzari
David E
DE
Peterson
Eric D
ED
Schulman
Kevin A
KA
Califf
Robert M
RM
D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000628:therapy*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction; D017239:Paclitaxel / Q000008:administration & dosage*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D020123:Sirolimus / Q000008:administration & dosage*; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D017239:Paclitaxel; D020123:Sirolimus