1. CYP2C19 Genotype Is Associated With Adverse Cardiovascular Outcomes in Black Patients Treated With Clopidogrel Undergoing Percutaneous Coronary Intervention.
- Author
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Tunehag KR, Thomas CD, Franchi F, Rossi JS, Keeley EC, Anderson RD, Beitelshees AL, Duarte JD, Gong Y, Kerensky RA, McDonough CW, Nguyen AB, Ortega-Paz L, Venkatesh S, Wang Y, Johnson JA, Winterstein AG, Stouffer GA, Angiolillo DJ, Cavallari LH, and Lee CR
- Subjects
- Aged, Female, Humans, Male, Middle Aged, Acute Coronary Syndrome drug therapy, Acute Coronary Syndrome ethnology, Acute Coronary Syndrome therapy, Coronary Artery Disease ethnology, Coronary Artery Disease genetics, Coronary Artery Disease therapy, Genotype, Pharmacogenomic Variants, Retrospective Studies, Risk Assessment, Risk Factors, Treatment Outcome, Black or African American genetics, Clopidogrel adverse effects, Clopidogrel therapeutic use, Cytochrome P-450 CYP2C19 genetics, Cytochrome P-450 CYP2C19 metabolism, Hemorrhage chemically induced, Hemorrhage genetics, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors adverse effects, Platelet Aggregation Inhibitors therapeutic use
- Abstract
Background: Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of CYP2C19 genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear., Methods and Results: Adults among 5 institutions who self-identified as Black or African American, underwent PCI and clinical CYP2C19 genotyping, and were treated with clopidogrel were included. Data were abstracted from health records. Major atherothrombotic (composite of death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina) and bleeding event rates within 1 year after PCI were compared across CYP2C19 metabolizer groups using multivariable Cox regression adjusted for potential confounders and baseline variables meeting a threshold of P <0.10. The population included 567 Black patients treated with clopidogrel (median age, 62 years; 46% women; 70% with an acute coronary syndrome indication for PCI). Major atherothrombotic events rates were significantly higher among clopidogrel-treated intermediate and poor metabolizers (24 of 125 [19.2%]) versus patients treated with clopidogrel without a no function allele (43 of 442 [9.7%]; 35.1 versus 15.9 events per 100 person-years; adjusted hazard ratio, 2.00 [95% CI, 1.20-3.33], P =0.008). Bleeding event rates were low overall (23 of 567 [4.1%]) and did not differ among the metabolizer groups., Conclusions: Black patients with CYP2C19 intermediate and poor metabolizer phenotypes who are treated with clopidogrel exhibit increased risk of adverse cardiovascular outcomes after PCI in a real-world clinical setting. Bleeding outcomes should be interpreted cautiously. Prospective studies are needed to determine whether genotype-guided use of prasugrel or ticagrelor in intermediate and poor metabolizers improves outcomes in Black patients undergoing PCI.
- Published
- 2024
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