title: Pioglitazone and cardiovascular risk. A comprehensive meta-analysis of randomized clinical trials.
abstract: OBJECTIVE
  The aim of this meta-analysis of randomized clinical trials (RCT) was to assess whether pioglitazone is also associated with increased cardiovascular risk, as recently reported for rosiglitazone.
  
  
  METHODS
  RCT of pioglitazone were retrieved from Medline (any date up to 31 August 2007; English language only). Unpublished RCT were identified through http://www.clinicaltrials.gov or http://www.fda.gov websites, and results on cardiovascular outcomes were retrieved from investigators and/or sponsors, whenever possible. RCT were included in meta-analysis if pioglitazone was compared with other treatments (placebo, active comparators or no treatment) for at least 4 weeks. Ninety-four trials, 10 of which were unpublished, were retrieved; those included in the analysis, which excluded PROspective PioglitAzone Clinical Trial In MacroVascular Events (PROACTIVE), enrolled 11 268 and 9912 patients in the pioglitazone and comparator groups respectively. Data for analysis, extracted independently by two observers, included all-cause and cardiovascular mortality and incidence of non-fatal coronary events and heart failure. Proportions of outcome measures across treatment groups were compared by odds ratios (ORs) and 95% confidence interval.
  
  
  RESULTS
  Pioglitazone was associated with reduced all-cause mortality [OR 0.30 (0.14-0.63); p < 0.05], with no relevant effect on non-fatal coronary events. The observed increase in incidence of non-fatal heart failure was not statistically significant [OR 1.38 (0.90-2.12)].
  
  
  CONCLUSIONS
  The use of pioglitazone does not appear to be harmful in terms of cardiovascular events and all-cause deaths.
authors.affiliation: Department of Cardiovascular Medicine, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy. edoardo.mannucci@unifi.it
authors.forename: E
authors.initials: E
authors.lastname: Mannucci
authors.forename: M
authors.initials: M
authors.lastname: Monami
authors.forename: C
authors.initials: C
authors.lastname: Lamanna
authors.forename: G F
authors.initials: GF
authors.lastname: Gensini
authors.forename: N
authors.initials: N
authors.lastname: Marchionni
mesh_terms: D000368:Aged; D002423:Cause of Death; D003327:Coronary Disease / Q000139:chemically induced* / Q000401:mortality / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006333:Heart Failure / Q000139:chemically induced* / Q000401:mortality; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D008875:Middle Aged; D000077205:Pioglitazone; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D045162:Thiazolidinediones / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone