Abstract 11802: Clinical Implementation Of CYP2C19-genotype Guided Antiplatelet Therapy Reduces Cardiovascular Events After PCI

Introduction: Clopidogrel is bioactivated by CYP2C19, and the CYP2C19 loss-of-function (LOF) genotype leads to reduced clopidogrel effectiveness after percutaneous coronary intervention (PCI). We examined whether clinical implementation of CYP2C19 genotype-guided antiplatelet therapy (APT) reduces the risk for cardiovascular events after PCI. Methods: CYP2C19 genotyping post-PCI was implemented at UF Health Shands Hospital in July 2012, with alternative APT recommended for LOF allele carriers. Major adverse cardiovascular events (MACE, comprised of cardiovascular death, MI, stroke and stent thrombosis) over the 6 months after PCI were determined via medical record review. MACE was compared between LOF allele carriers switched to alternative APT (LOF-alternative) and both LOF allele carriers who remained on clopidogrel (LOF-clopidogrel) and non-LOF carriers (non-LOF) using Kaplan-Meier method with additional multivariable Cox regression analysis and propensity score adjustment in LOF groups. Results: Of 412 patients (80% with ACS) who underwent PCI and genotyping, 126 (31%) had a LOF allele and 68 (54%) of these received alternative APT (prasugrel n=57, ticagrelor n=8, triple dose clopidogrel n=3). On Kaplan-Meier analysis (Figure), there was a lower incidence of MACE in LOF-alternative vs. LOF-clopidogrel groups and no significant difference between the LOF-alternative and non-LOF groups. On multivariable Cox regression analysis with propensity score adjustment, there was reduced risk of MACE in LOF-alternative vs. LOF-clopidogrel patients (HR 0.09, 95% CI 0.01-0.84, p=0.035). In the LOF-clopidogrel group, the majority of events (83%) occurred within 30 days; all were in patients who presented with an ACS. Conclusion: Changing from clopidogrel to alternative APT after PCI in patients with the CYP2C19 LOF genotype reduces the risk for MACE. These data support CYP2C19 genotyping in patients undergoing PCI, especially in those with ACS.