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Aspirin and Clo..

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Dual antiplatelet therapy with aspirin (ASA) and clopidogrel in patients receiving coronary artery stents is associated with significant improvements in cardiovascular outcomes.1 In spite of these therapies, many patients still experience stent thrombosis or myocardial infarctions. It is now recognized that some patients' response to ASA or clopidogrel therapy, as measured by platelet function tests, is suboptimal. These patients appear to be at greater risk of adverse cardiac events than those who achieve an adequate response to antiplatelet therapy.

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Campo and colleagues recently published the results of the Long-Term Clinical Outcome Based on Aspirin and Clopidogrel Responsiveness Status After Elective Percutaneous Coronary Intervention study.2 This was a pre-specified substudy of the 3T/2R (Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel) trial.3 In total, 1,277 patients were screened for responsiveness to aspirin and/or clopidogrel using the VerifyNow system (Accumetrics, San Diego). The aspirin assay results are expressed as aspirin reaction unit (ARU). An ARU ≤ 550 indicates a full response to aspirin therapy, whereas an ARU > 550 indicates a poor responder. The VerifyNow P2Y12 assay was used to evaluate the effects of clopidogrel on the P2Y12 receptor. The results are expressed in P2Y12 reaction units (PRU). The P2Y12 assay determines the percentage of platelet inhibition (%PI) by clopidogrel. Full response to clopidogrel is indicated by a %PI ≥ 40%; a %PI < 40% identifies poor responders. The investigators defined patients as "full or poor responder to both" if they were screened for both aspirin and clopidogrel response; the nonspecific term "full or poor responders" identified patients evaluated for aspirin and/or clopidogrel response.

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All patients received 100 mg/day of aspirin indefinitely. Clopidogrel patients were given 75 mg/day for at least one month with stable coronary artery disease as an indication for PCI and receiving bare metal stent implantation. Unstable angina patients and/or those receiving drug-eluting stents took clopidogrel 75 mg/day for one year. The primary endpoint of this substudy was the 1-year frequency of death, myocardial infarction (MI), and stroke. Myocardial infarction is defined as creatine kinase-myocardial band (CK-MB) greater than or equal to 3 times the upper limit of normal (ULN) and troponin I/T ratio greater than or equal to 3 times the upper limit of normal (ULN). A landmark analysis was performed at 3 days to better evaluate periprocedural and late adverse events.

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Of the 826 that underwent PCI, 358 patients were screened for aspirin responsiveness, of whom 96 (26.8%) were poor responders to aspirin; of the 261 patients screened for clopidogrel responsiveness, 110 (42.1%) were poor responders. A total of 207 were screened for both and 44 (21.9%) were only clopidogrel poor responders, 3 (1.5%) patients were only aspirin poor responders, and 25 (12.1%) were poor responders to both. Of the 278 patients that were poor responders to aspirin and/or clopidogrel, 132 received treatment with GP IIb/IIIa inhibitors. In the 548 aspirin and/or clopidogrel full responder population, a total of 116 patients received GP IIb/IIIa inhibitors. The average age of the entire cohort was 71 years and the majority of patients were men (74%). In the 0 to day 3 landmark analysis, poor responders to aspirin and/or clopidogrel in the ...

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