학술논문
Effectiveness of Clopidogrel vs Alternative P2Y 12 Inhibitors Based on the ABCD-GENE Score.
Document Type
Academic Journal
Author
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.; Rossi JS; Division of Cardiology and McAllister Heart Institute, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.; Keeley EC; Division of Cardiovascular Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA.; Anderson RD; Division of Cardiovascular 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.; Duarte JD; Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA.; Ortega-Paz L; Division of Cardiology, Department of Medicine, College of Medicine-Jacksonville, University of Florida, Jacksonville, 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.; Kerensky RA; Division of Cardiovascular Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA.; Kulick N; 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.; McDonough CW; Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA.; Nguyen AB; Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.; Wang Y; Department of Pharmaceutical Outcomes and Policy and Center for Drug Evaluation and Safety, College of Pharmacy, University of Florida, Gainesville, Florida, 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.; Yang WE; 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.; Winterstein AG; Department of Pharmaceutical Outcomes and Policy and Center for Drug Evaluation and Safety, College of Pharmacy, 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.; 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. Electronic address: lcavallari@cop.ufl.edu.
Source
Publisher: Elsevier Biomedical Country of Publication: United States NLM ID: 8301365 Publication Model: Print Cited Medium: Internet ISSN: 1558-3597 (Electronic) Linking ISSN: 07351097 NLM ISO Abbreviation: J Am Coll Cardiol Subsets: MEDLINE
Subject
Language
English
Abstract
Background: An ABCD-GENE (age, body mass index, chronic kidney disease, diabetes, and CYP2C19 genetic variants) score ≥10 predicts reduced clopidogrel effectiveness, but its association with response to alternative therapy remains unclear.
Objectives: The aim of this study was to evaluate the association between ABCD-GENE score and the effectiveness of clopidogrel vs alternative P2Y12 inhibitor (prasugrel or ticagrelor) therapy after percutaneous coronary intervention (PCI).
Methods: A total of 4,335 patients who underwent PCI, CYP2C19 genotyping, and P2Y12 inhibitor treatment were included. The primary outcome was major atherothrombotic events (MAE) within 1 year after PCI. Cox regression was performed to assess event risk in clopidogrel-treated (reference) vs alternatively treated patients, with stabilized inverse probability weights derived from exposure propensity scores after stratifying by ABCD-GENE score and further by CYP2C19 loss-of-function (LOF) genotype.
Results: Among patients with scores <10 (n = 3,200), MAE was not different with alternative therapy vs clopidogrel (weighted HR: 0.89; 95% CI: 0.65-1.22; P = 0.475). The risk for MAE also did not significantly differ by treatment among patients with scores ≥10 (n = 1,135; weighted HR: 0.75; 95% CI: 0.51-1.11; P = 0.155). Among CYP2C19 LOF allele carriers, MAE risk appeared lower with alternative therapy in both the group with scores <10 (weighted HR: 0.50; 95% CI: 0.25-1.01; P = 0.052) and the group with scores ≥10 (weighted HR: 0.48; 95% CI: 0.29-0.80; P = 0.004), while there was no difference in the group with scores <10 and no LOF alleles (weighted HR: 1.03; 95% CI: 0.70-1.51; P = 0.885).
Conclusions: These data support the use of alternative therapy over clopidogrel in CYP2C19 LOF allele carriers after PCI, regardless of ABCD-GENE score, while clopidogrel is as effective as alternative therapy in non-LOF patients with scores <10.
Competing Interests: Funding Support and Author Disclosures This work was supported by the National Heart, Lung, and Blood Institute (grant R01HL149752) and the National Human Genome Research Institute (grant U01HG007269). Spartan Bioscience provided the genotyping platforms and kits for initial testing at the University of Florida Health Jacksonville site. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr Franchi has received consulting fees or honoraria from AstraZeneca, Bayer, and Sanofi; and has received research grants to his institution from PLx Pharma and the Scott R. MacKenzie Foundation. Dr Johnson is on the United Health Group scientific advisory board. Dr Winterstein has received consulting fees from Arbor Pharmaceuticals, Bayer KG, Ipsen, and Genentech; and has received funding to her institution for research for which she served as principal investigator from Merck Sharp & Dohme. Dr Angiolillo has received consulting fees or honoraria from Abbott, Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, CSL Behring, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, Novo Nordisk, PhaseBio, PLx Pharma, Pfizer, and Sanofi; and has received research grants to his institution from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry, Merck, Novartis, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
Objectives: The aim of this study was to evaluate the association between ABCD-GENE score and the effectiveness of clopidogrel vs alternative P2Y
Methods: A total of 4,335 patients who underwent PCI, CYP2C19 genotyping, and P2Y
Results: Among patients with scores <10 (n = 3,200), MAE was not different with alternative therapy vs clopidogrel (weighted HR: 0.89; 95% CI: 0.65-1.22; P = 0.475). The risk for MAE also did not significantly differ by treatment among patients with scores ≥10 (n = 1,135; weighted HR: 0.75; 95% CI: 0.51-1.11; P = 0.155). Among CYP2C19 LOF allele carriers, MAE risk appeared lower with alternative therapy in both the group with scores <10 (weighted HR: 0.50; 95% CI: 0.25-1.01; P = 0.052) and the group with scores ≥10 (weighted HR: 0.48; 95% CI: 0.29-0.80; P = 0.004), while there was no difference in the group with scores <10 and no LOF alleles (weighted HR: 1.03; 95% CI: 0.70-1.51; P = 0.885).
Conclusions: These data support the use of alternative therapy over clopidogrel in CYP2C19 LOF allele carriers after PCI, regardless of ABCD-GENE score, while clopidogrel is as effective as alternative therapy in non-LOF patients with scores <10.
Competing Interests: Funding Support and Author Disclosures This work was supported by the National Heart, Lung, and Blood Institute (grant R01HL149752) and the National Human Genome Research Institute (grant U01HG007269). Spartan Bioscience provided the genotyping platforms and kits for initial testing at the University of Florida Health Jacksonville site. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr Franchi has received consulting fees or honoraria from AstraZeneca, Bayer, and Sanofi; and has received research grants to his institution from PLx Pharma and the Scott R. MacKenzie Foundation. Dr Johnson is on the United Health Group scientific advisory board. Dr Winterstein has received consulting fees from Arbor Pharmaceuticals, Bayer KG, Ipsen, and Genentech; and has received funding to her institution for research for which she served as principal investigator from Merck Sharp & Dohme. Dr Angiolillo has received consulting fees or honoraria from Abbott, Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, CSL Behring, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, Novo Nordisk, PhaseBio, PLx Pharma, Pfizer, and Sanofi; and has received research grants to his institution from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry, Merck, Novartis, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)