2. Academic Validation
  3. Effectiveness of Clopidogrel vs Alternative P2Y12 Inhibitors Based on the ABCD-GENE Score

Effectiveness of Clopidogrel vs Alternative P2Y12 Inhibitors Based on the ABCD-GENE Score

  • J Am Coll Cardiol. 2024 Apr 16;83(15):1370-1381. doi: 10.1016/j.jacc.2024.02.015.
Cameron D Thomas 1,  Francesco Franchi 2,  Joseph S Rossi 3,  Ellen C Keeley 4,  R David Anderson 4,  Amber L Beitelshees 5,  Julio D Duarte 1,  Luis Ortega-Paz 2,  Yan Gong 1,  Richard A Kerensky 4,  Natasha Kulick 6,  Caitrin W McDonough 1,  Anh B Nguyen 7,  Yehua Wang 8,  Marshall Winget 7,  William E Yang 5,  Julie A Johnson 9,  Almut G Winterstein 8,  George A Stouffer 3,  Dominick J Angiolillo 2,  Craig R Lee 6,  Larisa H Cavallari 10
Affiliations

Affiliations

  • 1 Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
  • 2 Division of Cardiology, Department of Medicine, College of Medicine-Jacksonville, University of Florida, Jacksonville, Florida, USA.
  • 3 Division of Cardiology and McAllister Heart Institute, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • 4 Division of Cardiovascular Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA.
  • 5 Department of Medicine and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
  • 6 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.
  • 7 Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • 8 Department of Pharmaceutical Outcomes and Policy and Center for Drug Evaluation and Safety, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
  • 9 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.
  • 10 Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA. Electronic address: [email protected].
PMID: 38599713 DOI: 10.1016/j.jacc.2024.02.015
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.

Keywords

CYP2C19; clopidogrel; genetic testing; percutaneous coronary intervention; precision medicine.

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