CYP2C19 Polymorphism and Platelet Aggregation-Associated Risks in Atrial Fibrillation Patients Undergoing PCI

CYP2C19 genetic polymorphisms impact the antiplatelet effect of clopidogrel and associate with ischemic and bleeding risk in patients undergoing percutaneous coronary intervention (PCI). This study aimed to evaluate the association of CYP2C19 and platelet reactivity (PR) with these risks, in atrial fibrillation (AF) patients undergoing PCI, treated with an oral anticoagulation (OAC) and clopidogrel. This two-center prospective cohort study included patients with AF and OAC undergoing PCI. Carriers of ≥ 1 loss-of-function (LOF) allele were classified as poor/intermediate metabolizers (PM/IM), whereas carriers of ≥ 1 gain-of-function allele without LOF alleles were classified as rapid metabolizers (RM). PR was assessed by thromboelastography (TEG) and/or multiple electrode aggregometry (MEA). The primary outcome included death, MI, or stroke at 6 months ±2 weeks; the secondary outcome consisted of non-major clinically relevant (NMCR) or major bleeding. Among 283 patients (median age 78 years; 72% male), 73 (26%) were PM/IM, 108 (38%) were NM, and 102 (36%) were RM. PM/IM status was not significantly associated with the primary ischemic outcome (PM/IM: 6 [8.2%] vs. NM + RM: 16 [7.6%], p = 0.869), but any bleeding rates were numerically lower. While there was a trend for association of high platelet reactivity (HPR) with the ischemic outcome (OR 2.005 [95% CI 0.820-4.902], p = 0.127), low platelet reactivity (LPR) was associated with major bleeding (OR 2.646 [95% CI 1.075-6.509], p = 0.034). PM/IM status did not detect an increased ischemic risk but might, however, protect from bleeding risk in AF patients undergoing PCI. HPR might indicate a higher ischemic risk, while LPR was associated with major bleeding.