Received on July 25, 2008
Accepted on March 13, 2009

Hemostasis and Thrombosis

Dual Antiplatelet Drug Resistance Is a Risk Factor for Cardiovascular Events after Percutaneous Coronary Intervention

¹ Department of Medicine III, University of Heidelberg, Germany, and DIAneering, Diagnostics Engineering & Research GmbH, Heidelberg, Germany
² Department of Medicine III, University of Heidelberg, Germany
³ Department of Cardiology and Angiology, University of Menofia, Shebeen Elkom, Egypt
⁴ Department of Medicine III, University of Tuebingen, Germany

^* To whom correspondence should be addressed. E-mail: boris.ivandic{at}med.uni-heidelberg.de.

BACKGROUND: Nonresponsiveness to clopidogrel and acetylsalicylic acid (ASA), a frequent result of platelet aggregometry studies, has unclear clinical and prognostic significance.

METHODS: We performed impedance aggregometry in 182 patients 12–24 h after percutaneous coronary intervention (PCI) and a 600-mg loading dose of clopidogrel, adding 5 µmol/L ADP and 1 mg/L collagen to diluted whole blood to determine platelet inhibition by clopidogrel and ASA, respectively. Samples from nonresponders were incubated in vitro with methyl-S-adenosine monophosphate or ASA to distinguish between pharmacodynamic and pharmacokinetic types of resistance. We assessed a combined primary endpoint of myocardial infarction, target vessel revascularization, late stent thrombosis, or cardiac death.

RESULTS: Nineteen patients (10.4%) were dual nonresponders (nonresponsive to both ASA and clopidogrel), and 163 patients (89.6%) were designated responders. The latter group also included 15 and 14 single nonresponders (responsive to either clopidogrel or ASA, respectively), who exhibited endpoint frequencies comparable to those of full responders (n = 134). Pharmacokinetic resistance was most prevalent. Primary endpoints occurred more frequently in dual nonresponders (n = 6, 31.6%) than in responders (n = 20, 12.3%) (relative risk 2.57; 95% CI 1.18–5.61; log-rank P = 0.03). Multivariate analysis confirmed dual nonresponsiveness (hazard ratio 2.9; 95% CI 1.17–7.2; P = 0.02) as an independent risk factor.

CONCLUSIONS: Dual nonresponders carry a high cardiovascular risk after PCI and should obtain intensified antiplatelet therapy and follow-up.