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CLINICAL RESEARCH: INTERVENTIONAL CARDIOLOGY

Increased Risk in Patients With High Platelet Aggregation Receiving Chronic Clopidogrel Therapy Undergoing Percutaneous Coronary Intervention

Is the Current Antiplatelet Therapy Adequate?

Sinai Center for Thrombosis Research, Baltimore, Maryland

Manuscript received July 28, 2006; accepted October 1, 2006.

^_* Reprint requests and correspondence: Dr. Paul A. Gurbel, Sinai Center for Thrombosis Research, Hoffberger Building, Suite 56, 2401 West Belvedere Avenue, Baltimore, Maryland 21215. (Email: pgurbel{at}lifebridgehealth.org).

OBJECTIVES: We sought to determine whether patients receiving chronic clopidogrel therapy undergoing nonemergent stenting who display high on-treatment preprocedural platelet aggregation measured by standard light transmittance aggregometry and thrombelastography (TEG) will be at increased risk for poststenting ischemic events.

BACKGROUND: Patients exhibiting heightened platelet reactivity to adenosine diphosphate (ADP) might be at increased risk for recurrent ischemic events after coronary stenting.

METHODS: A total of 100 consecutive patients receiving chronic antiplatelet therapy consisting of aspirin (325 mg qd) and clopidogrel (75 mg qd) were studied before undergoing nonemergent stenting. Patients were followed for 1 year after coronary stenting for the occurrence of death, myocardial infarction, stent thrombosis, stroke, or ischemia requiring a hospital stay.

RESULTS: All patients were aspirin responsive. Patients with ischemic events (23 of 100, 23%) within 1 year had greater on-treatment prestent ADP-induced platelet aggregation than patients without ischemic events by aggregometry and TEG (p < 0.001 for both measurements). Of patients with an ischemic event, 70% and 87% displayed high on-treatment platelet reactivity at baseline by aggregometry and TEG, respectively. High on-treatment platelet reactivity as measured by aggregometry and TEG were the only variables significantly related to ischemic events (p < 0.001 for both assays). The administration of eptifibatide reduced periprocedural elevation in platelet reactivity, with no significant differences in bleeding events.

CONCLUSIONS: Patients receiving chronic clopidogrel therapy undergoing nonemergent percutaneous coronary intervention who exhibit high on-treatment ADP-induced platelet aggregation are at increased risk for postprocedural ischemic events. These findings might have implications for the alteration in clopidogrel maintenance dose and use of glycoprotein IIb/IIIa inhibitors in selected patients.

Abbreviations and Acronyms   AA = arachidonic acid   ADP = adenosine diphosphate   GP = glycoprotein   HPR = high on-treatment platelet reactivity   LTA = light transmittance aggregometry   NPR = normal on-treatment platelet reactivity   PCI = percutaneous coronary intervention   TEG = thrombelastograph(y)

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