CYP2C19 loss-of-function alleles and the use of omeprazole or esomeprazole increase the risk of cardiovascular outcomes in patients using clopidogrel – a real-world study

Abstract Background Patients carrying loss-of-function (LOF) variants of CYP2C19 or using the CYP2C19-inhibitors omeprazole esomeprazole cannot fully bioactivate clopidogrel, and thus are lacking optimal thrombosis prevention. However, clopidogrel is a relevant alternative to ticagrelor due its lower incidence hemorrhagic events cost. Purpose The purpose this study was investigate in real-life prospective patient cohort how influence cardiovascular (cardiovascular deaths, reinfarction strokes) patients clopidogrel. Methods A (N=1972) with acute coronary syndrome (ACS) (N=1302) symptomatic chronic disease (N=670) were followed for 365 days. Information purchased prescription drugs, hospital discharge, death registry available all patients. retrospectively genotyped CYP2C19*2, CYP2C19*3, CYP2C19*8 LOF variants. Results total 608 (30.8%) carried alleles. During days follow-up, 252 had recurring ischemic vascular event, either myocardial infarction (N=189), stroke (N=24) (N=39). Vascular significantly more frequent among carriers alleles [14.8% (95% CI 11.7–17.8] than non-carriers [10.8% 9.0–12.6)], p=0.016. Omeprazole use similar allele non-carriers, but inclusion their analysis strengthened association. common composite group who not 14.8% 12.2–17.3) vs 9.9% 8.0–11.9) p=0.002. There tendency towards risk complications (p=0.07). Conclusions impaired bioactivation concomitant at increased events. For care both genetics medication should be considered everyday further randomised studies. Funding Acknowledgement Type funding sources: None.