CYP2C19 phenotype in South‐East Asian Acute Coronary Syndrome patients and impact on major adverse cardiovascular events

Abstract

What is known and objective: Several Caucasian cohort studies have associated at least one loss-of-function CYP2C19 on Clopidogrel (LoF-Clopidogrel) with major adverse cardiovascular events (MACE), and only a couple have used Clinical Pharmacogenetics Implementation Consortium (CPIC ®) phenotype grouping to study the associations. We primarily aimed to study the impact of use of platelet reactivity testing to escalate antiplatelet therapy and secondarily to study the association of CPIC phenotype with MACE outcomes in SouthEast Asian Acute Coronary Syndrome (ACS) subjects. Method: A retrospective genotype study was performed on 238 percutaneous coronary intervention subjects, originally planned for escalation of antiplatelets using platelet reactivity testing. Results and discussion: There was no difference in MACE between the switched and unswitched groups; however, 'all bleeds' and 'clinically significant bleeds' (CSB) were statistically higher in the patients who were switched to prasugrel. The subgroup of patients who remained on clopidogrel (n = 199) were analysed using phenotype categories and MACE. Eleven percent (11.4%) of CYP2C19 poor metabolizers (PM) suffered MACE, compared with 1.3% of extensive metabolizers (EM). LoF-Clopidogrel patients are significantly more likely to experience MACE compared with non-LoF subjects (8.0% vs 5.4%, P: .041). What is new and conclusion: In our multivariate analysis, LoF-Clopidogrel, malay ethnicity, diabetics and use of proton pump inhibitors were independent predictors of MACE. There were numerically more bleeds in LoF subjects who were on prasugrel compared with Clopidogrel (23.5% vs 11%, P = .082). Our data corroborate with current findings on platelet reactivity testing, suggesting that the assay would not be sensitive enough to pick up sufficient 'at-risk' subjects as compared to the use of CYP2C19 genotyping.

CYP2C19 loss-of-function alleles predicts clinical outcomes in East Asian patients with acute myocardial infarction undergoing percutaneous coronary intervention and stenting receiving clopidogrel

“…Our result addresses the knowledge gap for patients in Southeast Asia with CYP2C19 LOF alleles using clopidogrel after PCI. The results are consistent with the Singapore cohort ( 21 ), which revealed that LOF patients were significantly more likely to experience MACE compared to non-LOF subjects in acute coronary syndrome (8.0 vs. 5.4%, p = 0.041). In patients without ACS, another smaller cohort in Malaysia recruited patients who underwent elective PCI ( 20 ).…”

“…The relationship between CYP2C19 LOF alleles in patients with AMI using clopidogrel and clinical events has been studied in Northeast Asia, whereas studies in Southeast Asia are limited ( 20 , 21 ). In Taiwan, although the location was near northeast Asian, the island of Southeast Asia (ISEA) ancestry was one of the major genetic ancestries in Taiwan.…”

Validating the Prognostic Utility of the ABCD-GENE Score in Asian Patients with Acute Coronary Syndrome Patients on Clopidogrel

“…12,13 The greater risk of MACE in Asian patients than in white patients was hardly surprising, given that the prevalence of CYP2C19 LoF is almost twice that in Asian than in white populations. 9 In our adjusted model, we also identified additional factors associated with MACE, including baseline LDL, female sex, and history of ACS and ARB use. Notably, every 0.1 mmol/l increase in baseline LDL elevates MACE risk by 89% in our cohort.…”