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CYP2C19 phenotype in South‐East Asian Acute Coronary Syndrome patients and impact on major adverse cardiovascular events
Author(s) -
Tan Doreen SuYin,
Aw Jernice Wan Xin,
Winther Michael,
Goh Liuh Ling,
Ong Hean Yee,
Wee Eric,
Liu Jianjun,
Ho Han Kiat
Publication year - 2020
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/jcpt.13062
Subject(s) - clopidogrel , mace , prasugrel , cyp2c19 , medicine , acute coronary syndrome , percutaneous coronary intervention , cardiology , aspirin , myocardial infarction , cytochrome p450 , metabolism
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 South‐East 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.