title: Efficacy and safety of P2Y12 inhibitors according to diabetes, age, gender, body mass index and body weight: systematic review and meta-analyses of randomized clinical trials.
abstract: OBJECTIVE
  The efficacy of antiplatelet drugs may differ in specific patient subgroups. We aimed to assess the efficacy and safety of the P2Y12 inhibitors clopidogrel, ticlopidine, prasugrel, ticagrelor, and cangrelor according to diabetes status, age, gender, body mass index, and body weight.
  
  
  METHODS
  Randomized clinical trials (RCTs) of P2Y12 inhibitors reporting information on cardiovascular disease (defined as myocardial infarction, stroke, or cardiovascular death) and bleeding (defined as any bleeding) events among the subgroups diabetes and non-diabetes, age ≥65 and <65 year-old, men and women, body mass index ≥30 and <30 kg/m(2), and body weight ≥60 and <60 kg, were identified in Medline, Embase, Web of Science, and Cochrane Library on August 31st, 2014. For each inhibitor, random-effects meta-analyses were used to estimate the ratio of relative risks (rRR) for cardiovascular and bleeding events among patient subgroups.
  
  
  RESULTS
  Twenty distinct RCTs (233 285 participants, 21 323 cardiovascular and 5183 bleeding events) were identified. Cardiovascular risk reduction with clopidogrel did not significantly differ according to diabetes (rRR: 1.04; 95% CI: 0.95 to 1.13; p = 0.395), age (0.98; 0.88 to 1.09; p = 0.347), gender (0.97; 0.90 to 1.04; p = 0.382), or body mass index (1.11, 0.95 to 1.31; p = 0.191). Results for other inhibitors were comparable, although available data were sparse. Limited data on bleeding events were available.
  
  
  CONCLUSIONS
  Data from RCTs did not show a different cardiovascular efficacy of clopidogrel in diabetes mellitus and other clinically relevant subgroups. Limited information was available on the efficacy and safety of other P2Y12 inhibitors in specific subgroups.
authors.affiliation: Institute of Internal Medicine and Diabetes Care Unit, Catholic University School of Medicine, Rome, Italy; Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. Electronic address: frazac@fastwebnet.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Zaccardi
authors.affiliation: Institute of Internal Medicine and Diabetes Care Unit, Catholic University School of Medicine, Rome, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Pitocco
authors.affiliation: Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Willeit
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jari A
authors.initials: JA
authors.lastname: Laukkanen
mesh_terms: D000367:Age Factors; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015992:Body Mass Index; D001835:Body Weight; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D004351:Drug Resistance; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D016017:Odds Ratio; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects*; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12
keywords: Antiplatelet resistance; Clopidogrel; Diabetes; Meta-analysis; P2Y(12) inhibitors; Thienopyridines