Along with aspirin, clopidogrel has been a widely used antiplatelet therapeutic regimen. Although generally well tolerated, its efficacy varies among individuals, with the main hypothesis that its bioavailability relies on its bioconversion to the active compound, which, in turn, depends on the genetic background and/or interactions with other drugs. To determine which factors influenced response in our patients, 368 patients receiving combined antiaggregation therapy with aspirin and clopidogrel were followed for 1 year to record 30 novel cardiovascular acute events. This clinical relapse was considered a surrogate end point to measure therapeutic response under the influence of the CYP2C19*2, *3, and *17 and CYP3A5*3 alleles, as well as the effects of concomitant medication and the presence of known cardiovascular risk factors and comorbidity. We show that either single CYP2C19 or CYP3A5 genotyping or combined were not useful to predict clinical efficacy in this cohort. Rather than genetic testing, we have found that clinical observations such as suffering type 2 diabetes mellitus requiring insulin, having several vessels affected, and concurrent medication with calcium channel blockers, regardless of CYP3A5 genotype or drug class were, in that order, the strongest independent predictors of disease relapse.
Keywords: CYP2C19; CYP3A5; aspirin; calcium channel blockers; clopidogrel; diabetes.
© 2018, The American College of Clinical Pharmacology.