Impact of the ABCD-GENE Score on Clopidogrel Clinical Effectiveness after PCI: A Multi-Site, Real-World Investigation.

Autor: Thomas CD; Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA., Franchi F; Division of Cardiology, Department of Medicine, College of Medicine-Jacksonville, University of Florida, Jacksonville, Florida, USA., Keeley EC; Division of Cardiovascular Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA., Rossi JS; Division of Cardiology and McAllister Heart Institute, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Winget M; Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., David Anderson R; Division of Cardiovascular Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA., Dempsey AL; Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA., Gong Y; Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA., Gower MN; Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Kerensky RA; Division of Cardiovascular Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA., Kulick N; Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Malave JG; Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA., McDonough CW; Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA., Mulrenin IR; Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Starostik P; Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA., Beitelshees AL; Department of Medicine and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA., Johnson JA; Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA.; Division of Cardiovascular Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA., Stouffer GA; Division of Cardiology and McAllister Heart Institute, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Winterstein AG; Department of Pharmaceutical Outcomes & Policy and Center for Drug Evaluation and Safety, College of Pharmacy, University of Florida, Gainesville, Florida, USA., Angiolillo DJ; Division of Cardiology, Department of Medicine, College of Medicine-Jacksonville, University of Florida, Jacksonville, Florida, USA., Lee CR; Division of Cardiology and McAllister Heart Institute, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.; Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Cavallari LH; Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Jazyk: angličtina
Zdroj: Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2022 Jul; Vol. 112 (1), pp. 146-155. Date of Electronic Publication: 2022 May 02.
DOI: 10.1002/cpt.2612
Abstrakt: The Age, Body mass index, Chronic kidney disease, Diabetes mellitus, and CYP2C19 GENEtic variants (ABCD-GENE) score was developed to identify patients at risk for diminished antiplatelet effects with clopidogrel after percutaneous coronary intervention (PCI). The objective of this study was to validate the ability of the ABCD-GENE score to predict the risk for atherothrombotic events in a diverse, real-world population of clopidogrel-treated patients who underwent PCI and received clinical CYP2C19 genotyping to guide antiplatelet therapy. A total of 2,341 adult patients who underwent PCI, were genotyped for CYP2C19, and received treatment with clopidogrel across four institutions were included (mean age 64 ± 12 years, 35% women, and 20% Black). The primary outcome was major atherothrombotic events, defined as the composite of all-cause death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina within 12 months following PCI. Major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, myocardial infarction, ischemic stroke, or stent thrombosis, was assessed as the secondary outcome. Outcomes were compared between patients with an ABCD-GENE score ≥ 10 vs. < 10. The risk of major atherothrombotic events was higher in patients with an ABCD-GENE score ≥ 10 (n = 505) vs. < 10 (n = 1,836; 24.6 vs. 14.7 events per 100 patient-years, adjusted hazard ratio (HR) 1.66, 95% confidence interval (CI), 1.23-2.25, P < 0.001). The risk for MACE was also higher among patients with a score ≥ 10 vs. < 10 (16.7 vs. 10.1 events per 100 patient-years, adjusted HR 1.59, 95% CI 1.11-2.30, P = 0.013). Our diverse, real-world data demonstrate diminished clopidogrel effectiveness in post-PCI patients with an ABCD-GENE score ≥ 10.
(© 2022 The Authors. Clinical Pharmacology & Therapeutics © 2022 American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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