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Effectiveness of Clopidogrel vs Alternative P2Y12 Inhibitors Based on the ABCD-GENE Score
Cameron D Thomas1, Francesco Franchi2, Joseph S Rossi3
1Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Insights
Alternative P2Y12 inhibitor therapy is recommended over clopidogrel for patients with CYP2C19 loss-of-function alleles after percutaneous coronary intervention (PCI). Clopidogrel is equally effective as alternative therapies for non-LOF patients with low ABCD-GENE scores.
Area of Science:
- Cardiology
- Pharmacogenomics
- Interventional Cardiology
Background:
- The ABCD-GENE score (age, BMI, CKD, diabetes, CYP2C19 variants) predicts clopidogrel response, but its impact on alternative P2Y12 inhibitors is unknown.
- Percutaneous coronary intervention (PCI) patients require effective antiplatelet therapy.
Purpose of the Study:
- To assess the association between ABCD-GENE score and the effectiveness of clopidogrel versus alternative P2Y12 inhibitors (prasugrel, ticagrelor) post-PCI.
- To determine optimal P2Y12 inhibitor selection based on ABCD-GENE score and CYP2C19 genotype.
Main Methods:
- Analysis of 4,335 patients undergoing PCI, CYP2C19 genotyping, and P2Y12 inhibitor treatment.
- Primary outcome: major atherothrombotic events (MAE) within 1 year.
- Cox regression with inverse probability weighting, stratified by ABCD-GENE score and CYP2C19 loss-of-function (LOF) status.
Main Results:
- No significant difference in MAE between alternative therapy and clopidogrel for patients with ABCD-GENE score <10 or ≥10.
- Among CYP2C19 LOF carriers, alternative therapy showed a trend towards lower MAE (score <10) and significantly lower MAE (score ≥10).
- No difference in MAE between therapies for non-LOF patients with scores <10.
Conclusions:
- Alternative P2Y12 inhibitors are favored over clopidogrel in CYP2C19 LOF carriers post-PCI, irrespective of ABCD-GENE score.
- Clopidogrel demonstrates comparable effectiveness to alternative therapies in non-LOF patients with ABCD-GENE scores <10.
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.
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