title: The effect of pioglitazone on recurrent myocardial infarction in 2,445 patients with type 2 diabetes and previous myocardial infarction: results from the PROactive (PROactive 05) Study.
abstract: OBJECTIVE
  This analysis from the PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events) study assesses the effects of pioglitazone on mortality and macrovascular morbidity in patients with type 2 diabetes and a previous myocardial infarction (MI).
  
  
  BACKGROUND
  People with type 2 diabetes have an increased incidence of MI compared with the general population. Those with diabetes and MI have a worse prognosis than nondiabetic patients with cardiovascular disease.
  
  
  METHODS
  The PROactive study was a prospective, multicenter, double-blind, placebo-controlled trial of 5,238 patients with type 2 diabetes and macrovascular disease. Patients were randomized to either pioglitazone or placebo in addition to their other glucose-lowering and cardiovascular medication. Treatment of diabetes, dyslipidemia, and hypertension was encouraged according to the International Diabetes Federation guidelines. Patients were followed for a mean of 2.85 years. The primary end point was the time to first occurrence of macrovascular events or death. Of the total cohort, the subgroup of patients who had a previous MI (n = 2,445 [46.7%]; n = 1,230 in the pioglitazone group and n = 1,215 in the placebo group) was evaluated using prespecified and post-hoc analyses.
  
  
  RESULTS
  Pioglitazone had a statistically significant beneficial effect on the prespecified end point of fatal and nonfatal MI (28% risk reduction [RR]; p = 0.045) and acute coronary syndrome (ACS) (37% RR; p = 0.035). There was a 19% RR in the cardiac composite end point of nonfatal MI (excluding silent MI), coronary revascularization, ACS, and cardiac death (p = 0.033). The difference in the primary end point defined in the main PROactive study did not reach significance in the MI population (12% RR; p = 0.135). The rates of heart failure requiring hospitalization were 7.5% (92 of 1,230) with pioglitazone and 5.2% (63 of 1,215) with placebo. Fatal heart failure rates were similar (1.4% [17 of the 92] with pioglitazone versus 0.9% [11 of the 63] with placebo).
  
  
  CONCLUSIONS
  In high-risk patients with type 2 diabetes and previous MI, pioglitazone significantly reduced the occurrence of fatal and nonfatal MI and ACS. (PROspective pioglitAzone Clinical Trial In macroVascular Events; http://www.clinicaltrials.gov/ct/show/NCT00174993?order = 1; ISRCTN NCT00174993).
authors.affiliation: Medizinische Klinik III der Universität zu Köln, Köln, Germany. erland.erdmann@uni-koeln.de
authors.forename: Erland
authors.initials: E
authors.lastname: Erdmann
authors.forename: John A
authors.initials: JA
authors.lastname: Dormandy
authors.forename: Bernard
authors.initials: B
authors.lastname: Charbonnel
authors.forename: Massimo
authors.initials: M
authors.lastname: Massi-Benedetti
authors.forename: Ian K
authors.initials: IK
authors.lastname: Moules
authors.forename: Allan M
authors.initials: AM
authors.lastname: Skene
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology* / Q000401:mortality / Q000517:prevention & control*; D000077205:Pioglitazone; D011446:Prospective Studies; D055502:Secondary Prevention; D015996:Survival Rate; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone