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

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.