CYP2C19*2 genetic polymorphism and incidence of in-stent restenosis in patients on clopidogrel: A matched case-control study

Abstract Background: The cytochrome P450 2C19 *2 ( CYP2C19*2 ) genetic polymorphism is associated with reduced clopidogrel bioactivation, increasing the risk of atherothrombotic complications after percutaneous coronary intervention (PCI). In-stent restenosis (ISR) is a complication that limits the long-term prognosis of PCI. Objective: To investigate the association between CYP2C19*2 and ISR within one-year after PCI in patients prescribed dual antiplatelet therapy (DAPT) with aspirin and clopidogrel Setting: Acute general hospital, Malta Main outcome measure: Association between CYP2C19*2 and drug-eluting stent (DES)-ISR within one-year post-PCI in patients on DAPT with aspirin and clopidogrel Method: Sixty patients with angiographically-confirmed DES-ISR within one year when on DAPT with aspirin and clopidogrel were retrospectively identified (cases) and 60 patients with no documented ISR post-PCI in the study period (controls) were case-matched for age, gender, diabetes and estimated glomerular filtration rate value. Cases and controls were invited by cardiologists for CYP2C19*2 genotyping. The association between CYP2C19*2 and ISR was analysed using the Fisher’s Exact test and binary logistic regression. Results: Twenty-six (43.3%) cases and 5 (8.3%) controls were carriers of CYP2C19*2 , while 34 (56.7%) cases and 55 (91.7%) controls were non-carriers of CYP2C19*2 . The association between CYP2C19*2 carrier status and DES-ISR within one-year post-PCI was statistically significant (p<0.001) in both the univariate and multivariate analysis. Conclusion : The proportion of CYP2C19*2 carriers who presented with DES-ISR within one-year post-PCI while on clopidogrel was significantly higher compared to patients with no documented ISR.