Potential clinical utility of genetic and platelet function tests in patients on treatment with clopidogrel

Clopidogrel, a pro-drug whose active metabolite is an inhibitor of the platelet P2Y12 receptor, is used mostly for the prevention of cardiovascular events in patients with acute coronary syndromes undergoing percutaneous coronary interventions. However, clopidogrel is associated with great variability in antiplatelet response, mostly caused by variable efficacy of cytochrome P450 (CYP) isoforms, which convert clopidogrel to its active metabolite in a two-step process. Tailored treatment regimens that aim to transform all poor responders into responders have been proposed as a solution to poor responsiveness to clopidogrel. This tailored treatment is based on laboratory tests of platelet function (such as platelet aggregometry, the vasodilator-stimulated phosphoprotein phosphorylation assay and the VerifyNow P2Y12 assay) or genotyping of CYP. However, currently there is no agreement among platelet function tests in the identification of poor responders; moreover, no standardization of these tests or guidance on how to tailor treatment effectively based on their results is available. The alternative of identifying poor responders based on CYP genotyping is also unsatisfactory, as CYP genotypes account for only about 10% of individual response to the drug. Therefore, tailoring treatment of clopidogrel should not be implemented in the clinical setting yet.