European Heart Journal Advance Access originally published online on September 27, 2006
European Heart Journal 2006 27(20):2420-2425; doi:10.1093/eurheartj/ehl275
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Low response to clopidogrel is associated with cardiovascular outcome after coronary stent implantation
Medizinische Klinik III, Universitätsklinikum Tübingen, Eberhard Karls-Universität Tübingen, Otfried-Müller-Str. 10, D-72076 Tübingen, Germany
Received 3 March 2006; revised 21 August 2006; accepted 11 September 2006; online publish-ahead-of-print 27 September 2006.
* Corresponding author. Tel: +49 7071 29 83688; fax: +49 7071 29 5749. E-mail address: meinrad.gawaz{at}med.uni-tuebingen.de
Aims To assess whether low response to clopidogrel influences cardiovascular outcome after coronary stent implantation in a consecutively measured cohort of patients with coronary stent implantation.
Methods and results A total of 379 consecutive patients with symptomatic coronary artery disease (CAD), (stable angina n=206 and acute coronary syndrome, n=173) treated with percutaneous coronary stenting were enrolled in this trial. Responsiveness to clopidogrel was assessed by ADP (20 µmol/L)-induced aggregometry at least 6 h (mean 34.8±25.9 h) after administration of a loading dose of 600 mg clopidogrel. Platelet inhibition <30% was defined as low response to clopidogrel. At 3-month follow-up, the primary outcome of a combined major cardiovascular event including non-fatal myocardial infarction, non-fatal ischaemic stroke, or cardiovascular death was evaluated. Twenty-two patients (5.8%) were classified as low responders. Compared with patients who adequately responded to clopidogrel, a low responder had a significantly higher risk of major cardiovascular events [22.7 vs. 5.6%; odds ratio, 4.9; 95% confidence interval (CI), 1.66–14.96; P=0.004]. After adjustment for other factors influencing cardiovascular outcome, low response to clopidogrel and severe left ventricular dysfunction were independently associated with a major cardiovascular event within 3 months (hazard ratio for low response to clopidogrel, 3.71; 95% CI, 1.08–12.69; P=0.037).
Conclusion Low response to clopidogrel in patients with symptomatic CAD treated by stenting significantly enhances the occurrence of cardiovascular events and death. The evaluation of low response to clopidogrel may help to identify patients at increased risk who may benefit from intensified antiplatelet strategy.
Key Words: Clopidogrel • Antiplatelet drug resistance • Platelets • Aggregation • Coronary artery disease
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