Post‐percutaneous coronary intervention CYP2C19 genotyping in an Irish population: The potential role in identifying clopidogrel therapy‐related bleeding risks

Abstract

AimsDual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) remains the standard of care. CYP2C19 genetic polymorphisms cause variable clopidogrel bioactivation. Increased function (CYP2C19*17) allele carriers (rapid metabolizers [RM] or ultrarapid metabolizers [UM]) are clopidogrel hyper‐responders, hence are more susceptible to clopidogrel‐related bleeding. Since current guidelines recommend against routine genotyping following PCI, data on the clinical utility of CYP2C19*17 genotype guided strategy are sparce. Our study provides real‐world data on the 12‐month follow‐up of CYP2C19 genotyping in patients post‐PCI.MethodsThis is a cohort study within an Irish population receiving 12‐month DAPT following PCI. It identifies the prevalence of CYP2C19 polymorphisms within an Irish population and describes the ischaemic and bleeding outcomes after 12 months of DAPT.ResultsA total of 129 patients were included with the following CYP2C19 polymorphism prevalence: 30.2% hyper‐responders (26.4% RM [1*/17*], 3.9% UM [17*/17*]) and 28.7% poor‐responders (22.5% IM [1*/2*], 3.9% IM [2*/17*], 2.3% PM [2*/2*]). A total of 53 and 76 patients received clopidogrel and ticagrelor, respectively. At 12 months, total bleeding incidence within the clopidogrel group was positively correlated with CYP2C19 activity: IM/PM (0.0%), NM (15.0%) and RM/UM (25.0%). The positive relationship showed a moderate association that was statistically significant: rτ = 0.28, P = 0.035.ConclusionsThe prevalence of CYP2C19 polymorphisms in Ireland is 58.9% (30.2% CYP2C19*17, 28.7% CYP2C19*2) with an approximately one in three chance of being a clopidogrel hyper‐responder. Positive correlation between bleeding and increasing CYP2C19 activity within the clopidogrel group (n = 53) suggests possible clinical utility of a genotype‐guided strategy identifying high bleeding risk with clopidogrel in CYP2C19*17 carriers, but further studies are required.