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J Am Coll Cardiol, 2007; 49:2312-2317, doi:10.1016/j.jacc.2007.01.094
(Published online 1 June 2007). © 2007 by the American College of Cardiology Foundation |
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Department of Cardiology, Careggi Hospital, Florence, Italy.
Manuscript received January 2, 2007; revised manuscript received January 26, 2007, accepted January 28, 2007.
* Reprint requests and correspondence: Dr. David Antoniucci, Division of Cardiology, Careggi Hospital, Viale Pieraccini, I-50134, Florence, Italy. (Email: david.antoniucci{at}virgilio.it).
Objectives: We sought to determine whether nonresponsiveness 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 nonresponsiveness 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 µmol 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: nonresponsiveness to clopidogrel (hazard ratio [HR] 3.08, 95% confidence interval [CI] 1.32 to 7.16; p = 0.009), left ventricular ejection fraction (HR 0.95, 95% CI 0.92 to 0.98; p = 0.001), total stent length (HR 1.01, 95% CI 1.00 to 1.02; p = 0.010), and ST-segment elevation acute myocardial infarction (HR 2.41, 95% CI 1.04 to 5.63; p = 0.041).
Conclusions: Nonresponsiveness to clopidogrel is a strong independent predictor of stent thrombosis in patients receiving sirolimus- or paclitaxel-eluting stents.
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