Original Research
Saturday, November 11, 2023
11:30 AM–01:00 PM
Abstract
Introduction: CYP2C19 intermediate and poor metabolizers (IM/PMs) carry a
CYP2C19 no function allele and exhibit diminished clopidogrel effectiveness and increased risk of major atherothrombotic events (MAE) after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity and primarily included patients of European and East Asian ancestry. Thus, the impact of
CYP2C19 genotype on cardiovascular outcomes in clopidogrel-treated Black patients remains unclear.
Research Question or Hypothesis: Do Black CYP2C19 IM/PMs treated with clopidogrel have increased MAE risk after PCI?
Study Design: Multi-center observational, cohort study
Methods: Adult patients of self-reported Black or African American race across five institutions who underwent PCI, were genotyped clinically for CYP2C19, and were treated with clopidogrel were included. Genotype and clinical data were abstracted from health records. Rates of MAE (composite of death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina) and a secondary outcome of major adverse cardiovascular events (MACE; cardiovascular death, myocardial infarction, ischemic stroke, or stent thrombosis) within 1-year post-PCI were compared across CYP2C19 metabolizer groups using multivariable Cox regression.
Results: The population included 569 Black clopidogrel-treated patients (median age 62 years, 46% female, 70% acute coronary syndrome indication for PCI). MAE rates were significantly higher among clopidogrel-treated IM/PMs (n=126) versus patients without a no function allele (n=443) (32.2 vs. 15.9 per 100 person-years; adjusted HR 1.89, 95% CI 1.12–3.19, p=0.017). MACE also occurred more frequently among IM/PMs (22.0 vs. 11.5 per 100 person-years, respectively; adjusted HR 1.79; 95% CI 0.96–3.35; p=0.069), although this difference was non-significant.
Conclusion: Black patients with CYP2C19 IM/PM metabolizer phenotypes who are treated with clopidogrel exhibit increased risk of adverse cardiovascular outcomes after PCI, suggesting that genotype-guided antiplatelet therapy may have clinical benefit in Black patients. Future studies are needed to determine whether genotype-guided use of prasugrel or ticagrelor improves outcomes in Black patients undergoing PCI.
Presenting Author
Kayla R. Tunehag PharmD, MSPHUNC Chapel Hill
Authors
Dominick J. Angiolillo MD, PhD
University of Florida
Amber L. Beitelshees PharmD, MPH
University of Maryland School of Medicine
Larisa H. Cavallari Pharm.D., BCPS, FCCP
University of Florida
Ellen C. Keeley MD, MS
University of Florida
Craig R. Lee PharmD, PhD, FCCP
UNC Eshelman School of Pharmacy, UNC-Chapel Hill
Francesco Franchi MD
University of Florida
Anh B. Nguyen PharmD
UNC Eshelman School of Pharmacy
Julio D. Duarte Pharm.D., Ph.D.
University of Florida, College of Pharmacy
Cameron D. Thomas Pharm.D.
UF College of Pharmacy
Sanjay Venkatesh MD
University of North Carolina at Chapel Hill
Joseph S. Rossi MD, MSCI
UNC Medical Center
George A. Stouffer MD
UNC School of Medicine