title: Role of phenotypic and genetic testing in managing clopidogrel therapy.
abstract: 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.
authors.affiliation: Population Health Research Institute, Hamilton, Canada;
authors.forename: Noel C
authors.initials: NC
authors.lastname: Chan
authors.affiliation: Population Health Research Institute, Hamilton, Canada; Thrombosis and Atherosclerosis Research Institute, Hamilton, Canada; Department of Medicine, McMaster University, Hamilton, Canada; and.
authors.forename: John W
authors.initials: JW
authors.lastname: Eikelboom
authors.affiliation: Thrombosis and Atherosclerosis Research Institute, Hamilton, Canada; Department of Medicine, McMaster University, Hamilton, Canada; and.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ginsberg
authors.affiliation: Population Health Research Institute, Hamilton, Canada; Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Mandy N
authors.initials: MN
authors.lastname: Lauw
authors.affiliation: Population Health Research Institute, Hamilton, Canada;
authors.forename: Thomas
authors.initials: T
authors.lastname: Vanassche
authors.affiliation: Thrombosis and Atherosclerosis Research Institute, Hamilton, Canada; Department of Medicine, McMaster University, Hamilton, Canada; and.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Weitz
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Canada; and.
authors.forename: Jack
authors.initials: J
authors.lastname: Hirsh
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D000241:Adenosine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D057915:Drug Substitution; D005820:Genetic Testing; D006801:Humans; D010879:Piperazines / Q000493:pharmacokinetics / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D000068799:Prasugrel Hydrochloride; D058921:Purinergic P2Y Receptor Antagonists / Q000493:pharmacokinetics / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D013876:Thiophenes / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D010879:Piperazines; D058921:Purinergic P2Y Receptor Antagonists; D013876:Thiophenes; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine