CYP2C19 phenotype in South-East Asian Acute Coronary Syndrome patients and impact on major adverse cardiovascular events
| Autor: | Liuh Ling Goh, Han Kiat Ho, Doreen Su-Yin Tan, Hean Yee Ong, Jianjun Liu, Michael Winther, Jernice Wan Xin Aw, Eric Wee |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
medicine.medical_specialty Acute coronary syndrome Prasugrel Genotype medicine.medical_treatment Hemorrhage CYP2C19 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine Percutaneous Coronary Intervention Asian People Internal medicine medicine Humans Pharmacology (medical) cardiovascular diseases 030212 general & internal medicine Acute Coronary Syndrome Aged Retrospective Studies Pharmacology business.industry Percutaneous coronary intervention Middle Aged Clopidogrel medicine.disease Cytochrome P-450 CYP2C19 Phenotype Cardiovascular Diseases Pharmacogenetics Female business Prasugrel Hydrochloride Mace Platelet Aggregation Inhibitors Cohort study medicine.drug |
| Zdroj: | Journal of clinical pharmacy and therapeuticsREFERENCES. 45(1) |
| ISSN: | 1365-2710 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|