Predicting clopidogrel response using DNA samples linked to an electronic health record.

Area of Science:

• Pharmacogenomics
• Cardiovascular Medicine
• Genetics

Background:

• Clopidogrel is a common antiplatelet medication used after myocardial infarction (MI) and percutaneous coronary intervention (PCI).
• Genetic variants in ABCB1 and CYP2C19 are known to affect clopidogrel efficacy.
• PON1 variants have been linked to stent thrombosis, but real-world validation is needed.

Purpose of the Study:

• To replicate the association of ABCB1, CYP2C19, and PON1 variants with recurrent cardiac events in a real-world patient population treated with clopidogrel.
• To evaluate the utility of electronic health records (EHRs) for pharmacogenomic research.

Main Methods:

• Utilized BioVU, a DNA repository linked to de-identified EHRs.
• Identified patients treated with clopidogrel after MI and/or PCI.
• Compared genetic variants in cases (recurrent cardiac events) and controls (no recurrent events).

Main Results:

• CYP2C19*2 (HR 1.54, P = 0.003) and ABCB1 (HR 1.28, P = 0.018) variants were significantly associated with recurrent cardiac events.
• No significant association was found for PON1 variants (HR 0.91, P = 0.370).
• Findings support the use of EHRs for pharmacogenomic studies.

Conclusions:

• Genetic variants in CYP2C19 and ABCB1 are confirmed predictors of clopidogrel treatment outcomes in a real-world setting.
• PON1 variants were not associated with recurrent cardiovascular events in this cohort.
• EHR-based pharmacogenomic studies are feasible and valuable for validating genetic associations.