Impact of platelet reactivity after clopidogrel administration on drug-eluting stent thrombosis

Objectives We sought to determine whether non responsiveness to clopidogrel as revealed by high in vitro post-treatment platelet reactivity is predictive of drug-eluting stent (DES) thrombosis. Background No data exist about the impact of non responsiveness to clopidogrel on the risk of DES thrombosis. Methods We conducted a prospective observational cohort study from July 2005 to August 2006 in an academic hospital. A total of 804 patients who had successful sirolimus- or paclitaxel-eluting stent implantation were assessed for post-treatment platelet reactivity after a loading dose of 600 mg of clopidogrel. Patients with platelet aggregation by 10 mu mol adenosine 5'-diphosphate >= 70% were defined as nonresponders. All patients received chronic dual antiplatelet treatment (aspirin 325 mg and clopidogrel 75 mg daily) for 6 months. The primary end point was the incidence of definite/probable early, subacute, and late stent thrombosis at 6-month follow-up. Results The incidence of 6-month definite/probable stent thrombosis was 3.1%. All stent thromboses were subacute or late. Of 804 patients, 105 (13%) were not responsive to clopidogrel. The incidence of stent thrombosis was 8.6% in nonresponders and 2.3% in responders (p < 0.001). By multivariate analysis, the predictors of stent thrombosis were as follows: non responsiveness to clopidogrel (hazard ratio [HR] 3.08, 95% confidence interval [Cl] 1.32 to 7.16; p = 0.009), left ventricular ejection fraction (HR 0.95, 95% Cl 0.92 to 0.98; p = 0.001), total stent length (HR 1.01, 95% Cl 1.00 to 1.02; p = 0.010), and ST-segment elevation acute myocardial infarction (HR 2.41, 95% Cl 1.04 to 5.63; p = 0.041). Conclusions Non responsiveness, to clopidogrel is a strong independent predictor of stent thrombosis in patients receiving sirolimus- or paclitaxel-eluting stents.