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\begin{document}

\title{Post-Percutaneous Coronary Intervention CYP2C19 Genotyping: The
Potential Role In Identifying Clopidogrel Therapy Related Bleeding Risks}



\author[1]{Bing Wei Thaddeus Soh}%
\author[1]{Ronan Cusack}%
\author[1]{Max Waters}%
\author[1]{Cormac O'Connor}%
\author[1]{Samer Arnous}%
\author[1]{Thomas Kiernan}%
\affil[1]{University Hospital Limerick}%


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  \date{May 18, 2024}


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\begin{abstract}
Aim Dual antiplatelet therapy (DAPT) after percutaneous coronary
intervention (PCI) remains the standard of care. CYP2C19 genetic
polymorphisms results in variable Clopidogrel bioactivation. Increased
function (CYP2C19*17) allele carriers (rapid metabolizers (RM) or
ultrarapid metabolizers (UM)), are Clopidogrel hyper-responders and
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 months of DAPT following PCI for ACS or
CCS. It identifies the prevalence of CYP2C19 polymorphisms within an
Irish population and describe the ischaemic and bleeding outcomes after
12 months of Clopidogrel 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*)). Total bleeding
incidence at 12-months increased from poor-responders (0.0\%) to
normal-responders (15.0\%), to hyper-responders (25.0\%). Compared to
poor-responders, hyper-responders were significantly more likely to
experience a bleeding event (25.0\% vs 0.0\%, P = 0.044). Conclusions
The prevalence of CYP2C19 polymorphisms in Ireland is 58.9\% (30.2\%
CYP2C19*17, 28.7\% CYP2C19*2) with approximately 1 in 3 chance of being
a Clopidogrel hyper-responder. The trend of increasing bleeding with
increasing CYP2C19 activity, suggests a genotype guided strategy may
have clinical utility identifying high-bleeding-risk with Clopidogrel in
CYP2C19*17 carriers but further studies are required.%
\end{abstract}%



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