Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement

Abstract

SummaryDual antiplatelet therapy with aspirin and clopidogrel decreases the rate of stent thrombosis in patients undergoing percutaneous coronary intervention (PCI). However, despite intensified antiplatelet treatment, up to 4.7% of the patients undergoing coronary stenting develop thrombotic stent occlusion, suggesting incomplete platelet inhibition due to clopidogrel resistance. We evaluated the percentage of clopidogrel nonresponders among 105 patients with coronary artery disease (CAD) undergoing elective PCI. All patients were treated regularly with aspirin 100 mg/d and received a loading dose of 600 mg clopidogrel followed by a maintenance dose of 75 mg/d before PCI. Clopidogrel non-responders were defined by an inhibition of ADP (5 and 20 μMol/L) induced platelet aggregation that was less than 10% when compared to baseline values 4 h after clopidogrel intake. Semi-responders were identified by an inhibition of 10 to 29%. Patients with an inhibition over 30% were regarded as responders. We found that 5 (ADP 5 μMol/L) to 11% (ADP 20 μMol/L) of the patients were non-responders and 9 to 26% were semi-responders. Among the group of nonresponders there were two incidents of subacute stent thrombosis after PCI. We conclude that a subgroup of patients undergoing PCI does not adequately respond to clopidogrel, which may correspond to the occurrence of thromboischemic complications. Point-of-care testing may help to identify these patients who may then benefit from an alternative antiplatelet therapy.

Investigating the Mechanisms of Hyporesponse to Antiplatelet Approaches

“…18 In a different population of patients regarded as nonresponders with stable angina who underwent PCI, a higher rate of subacute stent thrombosis was identified. 19 Variability in ADP-induced aggregation is well known in patients with coronary artery disease treated with ASA therapy. 20 Patients currently taking ASA therapy with low ADPinduced platelet aggregation who exhibit poor inhibition by clopidogrel may therefore remain at low ischemic risk.…”

Controversies in Antiplatelet Therapy for Patients With Cardiovascular Disease

“…22 As with aspirin, variable platelet aggregation inhibition after clopidogrel occurs among individuals; nonresponders to clopidogrel have been identified. 23,24 One major mechanism may be the failure of clopidogrel, a prodrug, to be metabolized to its active metabolite by hepatic cytochrome P450 (CYP) 3A4.…”

Dual Antiplatelet Therapy for Coronary Stenting

“…Of note, this correlated with only 2 incidents of stent thrombosis in patients who were nonresponders. 15 Compared with the 300-mg loading dose, more patients who received the 600-mg loading dose were found to be clopidogrel responders, but within each group, there was a significant interindividual response. 11…”