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CLINICAL RESEARCH: INTERVENTIONAL CARDIOLOGY

Aspirin and Clopidogrel Drug Response in Patients Undergoing Percutaneous Coronary Intervention

The Role of Dual Drug Resistance

Eli I. Lev, MD^_*, Rajnikant T. Patel, MD^_*, Kelly J. Maresh, RN, BSN^_*, Sasidhar Guthikonda, MD^_*, Juan Granada, MD^_*, Timothy DeLao, MLT^_*, Paul F. Bray, MD and Neal S. Kleiman, MD^_*,_*

^_* Cardiology Section, Methodist DeBakey Heart Center
Thrombosis Research Section, Department of Medicine, Baylor College of Medicine, Houston, Texas

Manuscript received June 17, 2005; revised manuscript received July 19, 2005, accepted August 2, 2005.

^_* Reprint requests and correspondence: Dr. Neal S. Kleiman, Cardiology Section, Methodist DeBakey Heart Center, Baylor College of Medicine, Mail Station F-1090, 6565 Fannin Street, Houston, Texas 77030 (Email: nkleiman{at}bcm.tmc.edu).

OBJECTIVES: We sought to evaluate the response to clopidogrel among aspirin-resistant versus aspirin-sensitive patients undergoing percutaneous coronary intervention (PCI).

BACKGROUND: Wide variability has been reported in response to aspirin and clopidogrel. There are limited data on the simultaneous responses to both drugs.

METHODS: Elective PCI patients (n = 150) who received aspirin for 1 week but not clopidogrel were included. All patients received bivalirudin during PCI. Blood samples were drawn at baseline and 20 to 24 h after a 300-mg clopidogrel dose. Aspirin resistance was defined by 2 of 3 criteria: rapid platelet function analyzer-ASA score 550, 5 µmol/l adenosine diphosphate (ADP)-induced aggregation 70%, and 0.5 mg/ml arachidonic acid-induced aggregation 20%. Clopidogrel resistance was defined as baseline minus post-treatment aggregation 10% in response to 5 and 20 µmol/l ADP.

RESULTS: Nineteen (12.7%) patients were resistant to aspirin and 36 (24%) to clopidogrel. Nine (47.4%) of the aspirin-resistant patients were also clopidogrel resistant. Aspirin-resistant patients were more likely to be women and have diabetes than were aspirin-sensitive patients. They also had lower response to clopidogrel, assessed by platelet aggregation and activation markers (flow cytometry-determined PAC-1 binding and P-selectin expression). Elevation of creatine kinase-myocardial band after stenting occurred more frequently in aspirin-resistant versus aspirin-sensitive patients (38.9% vs. 18.3%; p = 0.04) and in clopidogrel-resistant versus clopidogrel-sensitive patients (32.4% vs. 17.3%; p = 0.06).

CONCLUSIONS: Aspirin-resistant patients as a group have reduced response to clopidogrel. Furthermore, we have identified a unique group of dual drug-resistant patients who may be at increased risk for thrombotic complications after PCI.

Abbreviations and Acronyms   AA = arachidonic acid   ADP = adenosine diphosphate   ARU = aspirin reaction units   CK-MB = creatine kinase-myocardial band   GP = glycoprotein   MFI = mean fluorescence intensity   MI = myocardial infarction   PCI = percutaneous coronary intervention   RPFA-ASA = rapid platelet function assay-aspirin