CYP2C19 Polymorphisms and Clinical Outcomes Following Percutaneous Coronary Intervention (PCI) in the Million Veterans Program

BACKGROUND: CYP2C19 loss-of-function (LOF) alleles decrease the antiplatelet effect of clopidogrel following percutaneous coronary intervention (PCI) in patients presenting with acute coronary syndrome (ACS). The impact of genotype in stable ischemic heart disease (SIHD) is unclear. OBJECTIVES: Determine the association of CYP2C19 genotype with major adverse cardiac events (MACE) after PCI for ACS or SIHD. METHODS: Million Veterans Program (MVP) participants age <65 years with a PCI documented in the VA Clinical Assessment, Reporting and Tracking (CART) Program between 1/1/2009 to 9/30/2017, treated with clopidogrel were included. Time to MACE defined as the composite of all-cause death, stroke or myocardial infarction within 12 months following PCI. RESULTS: Among 4,461 Veterans (mean age 59.1 ± 5.1 years, 18% Black); 44% had ACS, 56% had SIHD and 29% carried a CYP2C19 LOF allele. 301 patients (6.7%) experienced MACE while being treated with clopidogrel, 155 (7.9%) in the ACS group and 146 (5.9%) in the SIHD group. Overall, MACE was not significantly different between LOF carriers vs. noncarriers (adjusted hazard ratio [HR] 1.18, confidence interval [95%CI] 0.97–1.45, p=0.096). Among patients presenting with ACS, MACE risk in LOF carriers versus non-carriers was numerically higher (HR 1.30, 95%CI 0.98–1.73, p=0.067). There was no difference in MACE risk in patients with SIHD (HR 1.09, 95%CI 0.82–1.44; p=0.565). CONCLUSIONS: CYP2C19 LOF carriers presenting with ACS treated with clopidogrel following PCI experienced a numerically greater elevated risk of MACE events. CYP2C19 LOF genotype is not associated with MACE among patients presenting with SIHD.