title: Challenges and limitations in the interpretation of systematic reviews: making sense of clopidogrel and CYP2C19 pharmacogenetics.
abstract: From 2010 to 2012, nine systematic reviews reported highly variable conclusions regarding the association between carriage of a cytochrome P450 2C19 loss-of-function allele and the risk of adverse cardiovascular (CV) events in individuals using clopidogrel. Possible contributors to the variable findings include differences in patient populations, CV end points, and statistical models utilized by the systematic reviews, as well as unexplained heterogeneity, inconsistent/incomplete reporting, and risk of publication bias with respect to the primary studies.
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia. michael.sorich@flinders.edu.au
authors.forename: M J
authors.initials: MJ
authors.lastname: Sorich
authors.forename: T M
authors.initials: TM
authors.lastname: Polasek
authors.forename: M D
authors.initials: MD
authors.lastname: Wiese
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000139:chemically induced; D002986:Clinical Trials as Topic / Q000592:standards; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D023381:Endpoint Determination; D005838:Genotype; D006801:Humans; D015201:Meta-Analysis as Topic; D015233:Models, Statistical; D018579:Patient Selection; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics; D017594:Publication Bias; D012107:Research Design / Q000592:standards; D012196:Review Literature as Topic; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine