Impact of Race on Profiles of Platelet Reactivity and Clinical Outcomes in Clopidogrel-Treated Participants

Abstract

Black individuals undergoing percutaneous coronary intervention (PCI) experience higher rates of major adverse cardiovascular events (MACE) than non-Black individuals. This study assessed the racial differences in platelet reactivity and clinical outcomes among clopidogrel-treated participants. Two cohorts were analyzed. The pharmacodynamic (PD) cohort involved patients with atherosclerotic cardiovascular disease on maintenance clopidogrel therapy undergoing platelet function testing. The primary outcome was high platelet reactivity (HPR, i.e., P2Y₁₂ reaction unit [PRU] > 208). The PCI cohort included participants undergoing PCI on clopidogrel-based dual antiplatelet therapy. The primary outcome was 1-year MACE, defined as the composite of cardiovascular death, myocardial infarction (MI), ischemic stroke, or stent thrombosis. Data on clinically significant bleeding and CYP2C19 genotyping alleles were collected. The PD and PCI cohorts included 728 (32.1% Black) and 2,770 (20.5% Black) participants, respectively. Black participants had higher PRU levels (184 [IQR 128-234] vs. 144 [IQR 88-195]; P < 0.001) and higher prevalence of HPR (39.3% vs. 20.6%; P < 0.001). Independent predictors of HPR included Black race, hemoglobin levels, and presence of CYP2C19 loss-of-function allele. In the PCI cohort, Black participants had a higher risk of MACE (HR 1.47; 95% CI 1.02-2.11; P = 0.037), primarily driven by MI (HR 1.71; 95% CI 1.09-2.67; P = 0.019), with no significant difference in clinically significant bleeding (HR 1.08; 95% CI 0.65-1.80; P = 0.768). Black participants on clopidogrel exhibit higher platelet reactivity, increased rates of HPR, and an elevated risk of MACE within 1 year after PCI, without significant differences in bleeding compared to non-Black participants.