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Published on: March 15, 2022
Mutational analysis clopidogrel resistance and platelet function in patients scheduled for coronary artery bypass
Mick Correll1, Christopher K Johnson, Giovanni Ferrari
1Department of Biostatistics and Computational Biology and Center for Cancer Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Insights
Genetic testing for clopidogrel response is unreliable. Mutations in CYP2C19 and ABCB1 genes do not accurately predict patient response to this antiplatelet medication.
Area of Science:
- Pharmacogenomics
- Cardiovascular Medicine
- Clinical Chemistry
Background:
- Clopidogrel is a widely used antiplatelet medication for preventing thrombotic events.
- A significant proportion of patients exhibit an inadequate response to clopidogrel therapy.
- Genetic variations in CYP2C19 and ABCB1 are known to influence clopidogrel metabolism and efficacy.
Purpose of the Study:
- To evaluate the clinical utility of genetic testing for CYP2C19 and ABCB1 mutations in predicting clopidogrel response.
- To compare the predictive accuracy of genetic assays versus functional assays for clopidogrel response.
Main Methods:
- Ultra-high throughput sequencing was employed to genotype 105 patients for mutations in CYP2C19 and ABCB1.
- Patient response data was correlated with genetic testing results.
- The predictive accuracy of genetic testing was calculated.
Main Results:
- Testing for CYP2C19 mutations predicted clopidogrel response with only 52.4% accuracy.
- Testing for ABCB1 gene mutations predicted response in 48.6% of patients.
- Neither genetic test accurately identified patients with adequate clopidogrel response.
Conclusions:
- Current genetic testing for CYP2C19 and ABCB1 is insufficient for reliably predicting clopidogrel response.
- Functional assays are currently more appropriate for clinical assessment of clopidogrel response.
- Further research is needed to identify additional genetic factors influencing clopidogrel efficacy.
Abstract:
Clopidogrel is an oral antiplatelet pro-drug prescribed to 40 million patients worldwide who are at risk for thrombotic events or receiving percutaneous coronary intervention (PCI). However about a fifth of patients treated with clopidogrel do not respond adequately to the drug. From a cohort of 105 patients on whom we had functional data on clopidogrel response, we used ultra-high throughput sequencing to assay mutations in CYP2C19 and ABCB1, the two genes genetically linked to respond. Testing for mutations in CYP2C19, as recommended by the FDA, only correctly predicted if a patient would respond to clopidogrel 52.4% of the time. Similarly, testing of the ABCB1 gene only correctly foretold response in 51 (48.6%) patients. These results are clinically relevant and suggest that until additional genetic factors are discovered that predict response more completely, functional assays are more appropriate for clinical use.
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