The P2Y12 inhibitors, clopidogrel, prasugrel and ticagrelor, are administered in fixed doses without laboratory monitoring. Randomized trials in acute coronary syndrome have shown that prasugrel and ticagrelor are more effective than standard dose clopidogrel. Nonetheless, standard dose clopidogrel remains widely used because it causes less bleeding and is less expensive. Patients treated with standard dose clopidogrel have substantial variability in platelet inhibition, which is partly explained by genetic polymorphisms encoding CYP2C19, the hepatic enzyme involved in biotransformation of clopidogrel to its active metabolite. Some advocate tailoring P2Y12 inhibitor therapy according to the results of routine laboratory testing. Although there is good evidence for analytic, biological and clinical validity of several phenotypic and genotypic biomarkers, the benefit of a management strategy that incorporates routine biomarker testing over standard of care without such testing remains unproven. Appropriately designed, adequately powered trials are needed, but face the challenges of feasibility, cost, and the progressive switch from clopidogrel to prasugrel or ticagrelor.

Copyright © 2014 American Society of Hematology.