title: Thiazolidinedione use is not associated with worse cardiovascular outcomes: a study in 28,332 high risk patients with diabetes in routine clinical practice: brief title: thiazolidinedione use and mortality.
abstract: OBJECTIVE
  Assess the cardiovascular safety of Thiazolidinediones (TZD) in routine clinical practice.
  
  
  BACKGROUND
  TZD are insulin-sensitizing antidiabetic drugs commonly used in type 2 diabetes, but their cardiovascular safety has been questioned. We examined the association between TZD use and major cardiovascular outcomes.
  
  
  METHODS
  We examined 2-year mortality, non-fatal myocardial infarction (MI), and congestive heart failure (CHF) rates among outpatients with high cardiovascular risk and diabetes according to TZD use in the REACH Registry. Multivariable adjustment and propensity scores were used in the analyses.
  
  
  RESULTS
  A total of 4997 out of 28,332 patients took TZDs at baseline. During follow-up, 1532 patients died. The mortality rates (95% confidence interval [CI]) were 6.5% (5.5-7.6) with TZD and 7.2% (6.33-8.06) without; adjusted hazard ratio (HR) was 1.06 (0.89-1.26, P=0.54). The lack of association with mortality was consistent across subgroups regardless of history of atherothrombosis or CHF. Rates of non-fatal MI (HR 1.10, 95% CI 0.83-1.45, P=0.50) and non-fatal CHF (HR 0.90, CI 0.75-1.09, P=0.27) were similar in users and non-users. TZD use was associated with an increased risk of CHF in patients aged >80 years (HR 1.59, CI 1.06-2.40, P=0.03).
  
  
  CONCLUSIONS
  Use of TZD was not associated with increased incidence of major cardiovascular events in patients with diabetes from this large registry. Older patients experienced an increased risk of CHF over the study interval. Limitations of this study include its observational design, and thus unmeasured confounders cannot be excluded.
authors.affiliation: INSERM, U-695, 75006, Paris, France. ronan.roussel@bch.aphp.fr
authors.forename: Ronan
authors.initials: R
authors.lastname: Roussel
authors.forename: Samy
authors.initials: S
authors.lastname: Hadjadj
authors.forename: Blandine
authors.initials: B
authors.lastname: Pasquet
authors.forename: Peter W F
authors.initials: PW
authors.lastname: Wilson
authors.forename: Sidney C
authors.initials: SC
authors.lastname: Smith
authors.forename: Shinya
authors.initials: S
authors.lastname: Goto
authors.forename: Florence
authors.initials: F
authors.lastname: Tubach
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.forename: Avi
authors.initials: A
authors.lastname: Porath
authors.forename: Michel
authors.initials: M
authors.lastname: Krempf
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.forename: P Gabriel
authors.initials: PG
authors.lastname: Steg
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000401:mortality; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000139:chemically induced / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced / Q000401:mortality*; D011446:Prospective Studies; D012042:Registries; D012307:Risk Factors; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D045162:Thiazolidinediones