EASD: Retrospective Review Suggests Cardioprotective Benefit with Pioglitazone (Actos)

AMSTERDAM, Sept. 19 -- Treatment regimens for type 2 diabetes that include pioglitazone (Actos) were associated with lower risk of stroke and myocardial infarction, claimed investigators for the drug's maker.
The analysis of insurance claims for more than 66,000 patients with type 2 diabetes revealed a relatively low incidence of both stroke (3.36% in the pioglitazone patients versus 4.22% in patients on other therapies) and MI (0.86% in the pioglitazone group versus 1.42% in controls), according to findings reported at the European Association for the Study of Diabetes meeting here.
Those differences, however, translated into adjusted relative risks among patients on pioglitazone of 0.80 (95% confidence interval, 0.7158 to 0.8932, P<0.0001) for stroke, and 0.62 (95% CI, 0.5031 to 0.7661, P<0.0001) for MI, reported Robert Spanheimer, M.D., senior director of diabetes and metabolism at Takeda, and colleagues, from the company.
Moreover, the retrospective findings appear to confirm a meta-analysis published earlier this month in the Journal of the American Medical Association. (See: Ups and Downs of Thiazolinediones for Diabetes Assessed by Dueling Meta-Analyses) In that study, pioglitazone appeared to reduce the risk of stroke, MI, or death by 18% (P=0.02).
A meta-analysis of rosiglitazone (Avandia) published in the same issue of JAMA revealed a 42% increased risk of non-fatal MI (P=0.02) among patients with type 2 diabetes who used rosiglitazone.
But both drugs were associated with significant increases in the risk of heart failure. For rosiglitazone, the increased risk was more than 200% (P<0.005) and for pioglitazone it was 41% (P=0.002).
Commenting last week on the JAMA papers, Dr. Spanheimer said the benefit reported for pioglitazone, "confirms the results of the prospective PROactive study and expands the patient population."
But he also cautioned that, because the 10% reduction in MI and stroke in the PROactive study was not statistically significant, the trial did not meet its primary endpoint. "Therefore, we cannot talk about efficacy in reducing macrovascular events."
In the current study, Dr. Spanheimer and colleagues searched the i3 Innovus database, which includes data on more than 27 million patients in managed care plans to identify patients treated for type 2 diabetes from 2003 through 2006.
They compared outcomes for 11,433 patients treated with pioglitazone with or without other therapies to 55,273 patients who received any antidiabetes therapy other than pioglitazone or rosiglitazone.
The outcome was the incidence of stroke or MI as defined by ICD-9 codes.
The index date was defined as the start date for the initial antidiabetes medication. Patients were included if they were 45 or older at the index date, had continuous enrollment data available for at least six months before and one month after the index date, and did not have a record of stroke or MI in the six months before the index date.
"We conclude that, in a clinical practice setting in patients with type 2 diabetes, therapies that include pioglitazone are associated with significant reductions in the risk for stroke or MI compared to non-thiazolidinedione therapies," they wrote.
The study was funded by Takeda. The authors are employees of the company. Primary source: European Association for the Study of Diabetes Annual Meeting
Source reference: Xu Y et al. "Risk of stroke and myocardial infarction is reduced in patients with type 2 diabetes treated with pioglitazone: results of a retrospective, claims-based study." Abstract 1257, presented Sept. 19.