High Platelet Reactivity Combined with CYP2C19 Genotype in Predicting Outcomes in East Asian Patients Undergoing Percutaneous Coronary Intervention

Abstract

Loss-of-function (LoF) alleles of cytochrome P450 2C19 (CYP2C19), which are prevalent in East Asians, are linked to high platelet reactivity (HPR) phenotype and poor prognosis. We aimed to investigate the incremental predictive value of HPR combined with CYP2C19 genotype in predicting outcomes after drug-eluting stent (DES) implantation. The patients treated with platelet function and genotype-related long-term prognosis in drug-eluting stent (PTRG-DES) consortium enrolled a total of 13,160 Korean patients treated with DES who had platelet function test (PFT) or CYP2C19 genotype, of which, 6,717 patients with PFT and genotype together were categorized. HPR was defined as VerifyNow ≥ 252 P2Y12 reaction unit. The primary outcome was the incidence of major adverse cardiac and cerebrovascular event (MACCE) 5 years after treatment. The patients with both HPR and CYP2C19 LoF/LoF had the highest MACCE rates (6.2%) and increased MACCE risk (adjusted hazard ratio: 1.89, 95% confidence interval: 1.20–2.91, P = 0.006) compared with those without both HPR and CYP2C19 LoF/LoF. There was no effect of interaction between HPR and CYP2C19 genotype on the primary outcome (P = 0.424). Adding combined HPR and CYP2C19 genotype to the conventional model had an incremental influence in predicting MACCE and stent thrombosis. Compared to the model including HPR or CYP2C19 genotype alone, a combination model significantly improved the risk stratification for stent thrombosis but not MACCE. In DES-treated East Asian patients, the combined evaluation of PFT results and CYP2C19 genotyping might improve risk prediction of ischemic events during clopidogrel treatment. © 2023 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.