Post-Percutaneous Coronary Intervention CYP2C19 Genotyping in an Irish population: The Potential Role in Identifying Clopidogrel Therapy Related Bleeding Risks.

AIM: 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 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 describe the ischaemic and bleeding outcomes after 12-month DAPT.

RESULTS: 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*)). 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%), RM/UM (25.0%). The positive relationship showed a moderate association that was statistically significant, r τ =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 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.