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

AIMS:Dual 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. METHODS:This 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. RESULTS:A 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. CONCLUSIONS:The 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.