COPENHAGEN — Pioglitazone (Actos) demonstrates a beneficial effect on a variety of measures of cardiovascular disease outcome in high-risk patients with type 2 diabetes, speakers said at the annual meeting of the European Association for the Study of Diabetes.
The data come from four subanalyses of the Eli Lilly and Takeda Global Research and Development's PROactive study.
In that study, 5,238 patients with type 2 diabetes and evidence of macrovascular disease were randomized to oral pioglitazone (maximum dose 45 mg/day) or placebo in addition to their other glucose-lowering drugs and other medications.
In a mean follow-up of 34.5 months, pioglitazone nonsignificantly reduced the risk of the composite primary end point of all-cause mortality, nonfatal myocardial infarction (MI), stroke, acute coronary syndrome (ACS), endovascular or surgical intervention in the coronary or leg arteries, and amputation above the ankle (10% relative risk reduction for experiencing one or more of those events). Pioglitazone significantly reduced the main secondary end point of all-cause mortality, nonfatal MI, and stroke (16% relative risk reduction).
At this year's meeting, Dr. Stuart R. Kupfer, senior medical director of clinical sciences, cardiovascular, at Takeda, in Lincolnshire, Ill., presented statistically significant findings for additional combined end points, including time to all-cause death, nonfatal MI, stroke, or ACS (17% relative risk reduction); cardiovascular (CV) death, MI, stroke, or ACS (18%); cardiovascular death, MI, stroke, or ACS (20%); and fatal or nonfatal MI (22%).
In a second study, presented by Dr. Robert Spanheimer, Takeda's director of diabetes and metabolism, medical and scientific affairs, pioglitazone therapy produced beneficial effects on patient lipid profiles during PROactive, with significantly greater mean decreases in triglycerides and mean increases in HDL cholesterol with pioglitazone, compared with insulin, metformin, and sulfonylurea (each analyzed separately). Triglycerides were reduced by 1.7% from baseline with pioglitazone while increasing 12.5% with placebo. For HDL cholesterol, the increase was 21.3% with pioglitazone vs. 11.3% with placebo. Although LDL cholesterol rose with pioglitazone (12.1% vs. 8.4% with placebo), the overall ratio of LDL-C:HDL-C was significantly improved.
A third analysis, presented in a poster by PROactive lead investigator Dr. John A. Dormandy, compared outcomes between the 984 study subjects who entered the study with a history of prior stroke and the 4,254 without prior stroke.
In those with prior stroke, pioglitazone significantly reduced the risk of recurrent stroke (5.6% vs. 10.2% with placebo), and of the combined end point CV death, MI, or stroke (13.0% vs. 17.7%). There was also a trend of benefit for other combined end points. Pioglitazone had no effect on subsequent strokes among the patients without previous stroke, noted Dr. Dormandy, of St. George's Hospital, London.
Dr. Erland Erdmann, of the University of Cologne, Germany, and chairman of the PROactive executive committee, reported in a poster that there was no significant impact of gender, age (less than 65 years vs. 65 and older), or diabetes duration (less than 5 years vs. 5 years and longer) on the hazard ratios for time to fatal or nonfatal MI, suggesting that “the best estimate for the reduction in risk of recurrent MI for each subgroup is given by that for the entire previous MI cohort.”