CYP2C19 status and risk of major adverse cardiovascular events in peripheral artery disease: Insights from the EUCLID Trial

Mutations in the CYP2C19 gene can affect the conversion of clopidogrel to its active metabolite, leading to varying degrees of platelet inhibition. Based on prior studies evaluating CYP2C19 gene polymorphisms in patients with acute coronary syndrome, we hypothesized that patients with peripheral artery disease (PAD) carrying loss of function (LoF) alleles could experience heightened rates of major adverse cardiac events and those carrying gain of function (GoF) alleles could experience increased rates of major bleeding compared with non-carriers.1-4 EUCLID (NCT01732822) was a double-blind, multicenter, randomized active-comparator trial of 13,885 patients with symptomatic PAD randomly assigned to receive ticagrelor (90 mg twice daily) or clopidogrel (75 mg daily). Eligible patients had to be ≥50 years of age and have symptomatic PAD defined as previous lower extremity revascularization >30 days before randomization or an ankle-brachial index (ABI) of ≤0.80.5