Genetic Testing of CYP2C19 in Prognostic Evaluation of Long-Term Major Adverse Cardiac and Vascular Events

Several studies have shown that the efficacy of clopidogrel for secondary prevention of major adverse cardiovascular events (MACE), including acute coronary syndrome, depends on the polymorphism of the CYP2C19 gene. However, studies with large sample sizes and long-term follow-up are missing. Moreover, the impact of this polymorphism on the risk of major adverse limb events (MALE), particularly in patients with peripheral artery disease of the lower limb, is unexplored. Additionally, the impact of CYP2C19 gene polymorphism on clopidogrel effectiveness in preventing recurrent stroke in diverse populations is unknown since most of the data are from Asian ancestry populations. We hypothesize that patients with CYP2C19 gene loss of function alleles are at high risk of MACE and MALE compared to those without loss of function alleles at long-term follow-up. We propose to assess MACE and MALE in a large cohort of patients with available CYP2C19 genotypes treated at the University of Florida Health to evaluate the impact of CYP2C19 gene polymorphisms on the risk of new or recurrent events at long-term follow-up. Our specific aims are Aim 1) to determine the impact of CYP2C19 gene polymorphisms (loss of function alleles vs. non-loss of function alleles) on the risk of MACE (a composite of all-cause death, non-fatal MI, and non-fatal stroke) at long-term follow-up; Aim 2) to evaluate the impact of CYP2C19 gene polymorphisms (loss of function alleles vs. non-loss of function alleles) on the risk of MALE (a composite of limb amputations, chronic threatening limb ischemia, acute limb ischemia, and limb revascularization) at long-term follow-up; and Aim 3) to evaluate the impact of CYP2C19 gene polymorphisms (loss of function alleles vs. non-loss of function alleles) on the risk of cerebrovascular events (CVE, a composite of any stroke and transient ischemic attack) at long-term follow-up.