Effects of pioglitazone on major adverse cardiovascular events in high-risk patients with type 2 diabetes: results from PROspective pioglitAzone Clinical Trial In macro Vascular Events (PROactive 10).
BACKGROUND
Composite end points of major adverse cardiovascular events (MACEs) are standard measures for comparing treatment in large cardiovascular outcome studies. This analysis from PROspective pioglitAzone Clinical Trial In macro Vascular Events (PROactive) evaluated the effects of pioglitazone on the prespecified MACE end point of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE1) and on 6 post hoc MACE composites (various combinations of all-cause, cardiovascular, or cardiac mortality; plus nonfatal myocardial infarction; plus nonfatal stroke; and/or acute coronary syndrome) in patients with type 2 diabetes.


METHODS
PROactive was a cardiovascular outcome study that randomized patients with type 2 diabetes to pioglitazone (n = 2605) or placebo (n = 2633), in addition to existing glucose-lowering and cardiovascular medications. Pioglitazone was titrated from 15 to 45 mg/d based upon tolerability. Mean follow-up was 34.5 months.


RESULTS
At final visit, 257 (9.9%) pioglitazone-treated and 313 (11.9%) placebo-treated patients had a first event that contributed to the MACE1 end point (hazard ratio 0.82, 95% CI 0.70-0.97, P = .0201). There were statistically significant differences in favor of pioglitazone in 5 of the other MACE end points (P < .05) and a trend to benefit in the sixth (P = .052), with hazard ratios of 0.79 to 0.83.


CONCLUSIONS
In patients with advanced type 2 diabetes at high risk for cardiovascular events, pioglitazone treatment resulted in significant risk reductions in MACE composite end points to 3 years.
Wilcox
Robert
R
Department of Cardiovascular Medicine, Queen's Medical Centre, University Hospital, Nottingham, United Kingdom. robert.wilcox@nottingham.ac.uk
Kupfer
Stuart
S
Erdmann
Erland
E
D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000401:mortality* / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D000077205:Pioglitazone; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology; D045162:Thiazolidinediones / Q000627:therapeutic use*
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone