CYP2C19 Polymorphisms and Clinical Outcomes Following Percutaneous Coronary Intervention in the Million Veteran
Catherine Chanfreau-Coffinier1, Kevin A Friede2, Mary E Plomondon3
1VA Salt Lake City Heath Care System, Salt Lake City, Utah, USA.
Clinical Pharmacology and Therapeutics
|June 3, 2025
Summary
CYP2C19 loss-of-function alleles may increase major adverse cardiac event risk for younger acute coronary syndrome patients on clopidogrel after PCI. Clinical factors are more critical for older patients with stable ischemic heart disease.
Area of Science:
- Cardiovascular Medicine
- Pharmacogenomics
- Interventional Cardiology
Background:
- CYP2C19 loss-of-function (LOF) alleles are known to reduce clopidogrel's antiplatelet efficacy in acute coronary syndrome (ACS) patients post-percutaneous coronary intervention (PCI).
- The influence of CYP2C19 genotype on outcomes in stable ischemic heart disease (SIHD) patients undergoing PCI in real-world settings remains less understood.
Purpose of the Study:
- To investigate the association between CYP2C19 LOF alleles and major adverse cardiac events (MACE) in a large, real-world cohort of Veterans undergoing PCI.
- To compare the impact of CYP2C19 genotype on MACE risk in patients with ACS versus SIHD.
Main Methods:
- A retrospective analysis of 9061 Veterans from the VA Million Veteran Program treated with clopidogrel post-PCI between 2009 and 2017.
- Major adverse cardiac event (MACE) was defined as cardiovascular death, stroke, or myocardial infarction within 12 months post-PCI.
- Genotyping for CYP2C19 LOF alleles was performed, and outcomes were analyzed based on ACS/SIHD status and genotype, with adjusted hazard ratios (aHR) calculated.
Main Results:
- Overall, 28% of patients carried a CYP2C19 LOF allele. A trend towards increased MACE risk was observed in LOF carriers (aHR 1.13).
- The risk was more pronounced in ACS patients (aHR 1.20), particularly younger individuals (<66 years) (aHR 1.41, P=0.028).
- No significant impact of CYP2C19 genotype on MACE risk was found in SIHD patients (aHR 1.09) or older ACS patients.
Conclusions:
- CYP2C19 LOF alleles may increase MACE risk in younger ACS patients treated with clopidogrel post-PCI.
- Clinical factors appear more significant than CYP2C19 genotype in determining MACE risk for older Veterans with ACS or any SIHD patients undergoing PCI.
- These findings highlight the complex interplay between genetics, clinical presentation, and antiplatelet therapy outcomes.
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