Abstract Body (Do not enter title and authors here): Introduction: Cytochrome P450 2C19 (CYP2C19) loss-of-function (LOF) genotypes reduce clopidogrel, but not prasugrel or ticagrelor, effectiveness following percutaneous coronary intervention (PCI). Accumulating evidence has demonstrated the clinical benefit of using CYP2C19 genotype to guide selection of P2Y12 inhibitor therapy after PCI. However, these studies have primarily included patients of European and East Asian ancestry. Therefore, there is a paucity of data on the impact of CYP2C19-guided antiplatelet therapy on clinical outcomes in Black patients.
Aim: We aimed to assess the impact of CYP2C19-guided P2Y12 inhibitor selection on risk for major atherothrombotic events (MAE) among self-reported Black patients within one-year post-PCI.
Methods: Black adults across five institutions who underwent PCI and clinical CYP2C19 genotyping for LOF alleles and were prescribed clopidogrel or an alternative P2Y12 inhibitor (prasugrel, ticagrelor) were included. The ultimate prescribing decision was at the prescriber’s discretion. Atherothrombotic events were manually abstracted from the electronic health record and adjudicated. The primary outcome, MAE (composite of all-cause mortality, myocardial infarction, ischemic stroke, stent thrombosis, or unstable angina requiring revascularization), was compared between patients treated with alternative P2Y12 inhibitors (irrespective of CYP2C19 status) versus LOF allele carriers treated with clopidogrel, and separately versus non-LOF carriers treated with clopidogrel, using multivariable Cox regression.
Results: The study population consisted of 1,244 Black patients (mean age 61±12 years; 44% women; 70% with acute coronary syndrome), with 734 patients prescribed clopidogrel (170 LOF-carriers, 564 non-LOF-carriers) and 510 prescribed an alternative inhibitor. MAE rates were higher in the LOF-clopidogrel vs alternative inhibitor group (29.1 vs. 13.9 events per 100 PY; unadjusted HR: 0.49 [95%CI: 0.31-0.77], p=<0.01; adjusted HR: 0.54 [95%CI: 0.32-0.91], p=0.02). MAE rates did not differ between the non-LOF-clopidogrel and alternative inhibitor groups (15.4 vs. 13.9 events per 100PY; unadjusted HR: 0.99 [95% CI:0.61-1.32], p=0.57; adjusted HR: 0.99 [95% CI:0.65-1.50], p=0.97).
Conclusion: These data suggest that clopidogrel is as effective as alternative P2Y12 inhibitors in post-PCI Black patients without a CYP2C19 LOF allele, while alternative therapy improves outcomes in LOF allele carriers.