Mutational analysis clopidogrel resistance and platelet function in patients scheduled for coronary artery bypass grafting

• Clopidogrel is an oral antiplatelet drug prescribed to 40 million patients worldwide.
• About a fifth of patients treated with clopidogrel do not respond adequately.
• We assayed mutations of CYP2C19 and ABCBI which have been linked to respond.
• Mutations in CYP2C19 predicted response in only 52.4% of patients.
• Mutations in ABCB1 gene only predicted response in 51 (48.6%) patients.

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.