Rosiglitazone (Avandia) poses no significant increased risk of death, stroke or heart attack, though it does increase the risk of fractures, according to a new analysis of 2,368 patients with cardiovascular disease and type 2 diabetes, according to findings presented this week at the American Diabetes Association's 70th scientific sessions in Orlando, Fla., and are part of the BARI 2D trial.

BARI 2D co-author Richard G. Bach, MD, medical director of the cardiac intensive care unit at Barnes-Jewish Hospital in St. Louis, presented this research June 29 in a late-breaking clinical studies session at ADA.

The safety of rosiglitazone has been a controversial topic since a 2007 meta-analysis published in the New England Journal of Medicine concluded that rosiglitazone was associated with a significant increase in the risk of MI and with an increase in the risk of death from cardiovascular causes. That study reviewed the results of 42 previously published investigations, but did not independently test the drug, which in the class of thiazolidinedione (TZD) drugs,.

In November 2007, the FDA added a warning label to the drug regarding potential heart risks, and the agency has a meeting planned this month that will review the safety of rosiglitazone.

This post-hoc analysis of the BARI 2D findings shows no increased risk of MI or cardiovascular death with rosiglitazone treatment. Analyzing 4.5 years of follow-up data for patients who were being treated with rosiglitazone, compared to those not taking any TZD drugs, the study found no increase in risk of death or heart attack from taking rosiglitazone. While no protective cardiovascular benefit was shown, the analysis found that the rate of death, heart attack and stroke tended to be lower—about 28 percent lower—among patients taking rosiglitazone.

The researchers also found that the rate of congestive heart failure was higher among patients taking rosiglitazone, but the difference was not statistically significant. Also seen in previous studies, the analysis of BARI 2D reported a 45 percent increase in fracture rates for those taking rosiglitazone, compared to those not taking any TZD medications.

"These data are important because they suggest there is no significant cardiovascular harm posed by taking rosiglitazone for patients with type 2 diabetes and coronary heart disease," said Bach. "There is an increase in fractures, but when one considers the dramatic morbidity and mortality associated with ischemic cardiovascular events in patients with diabetes, these data are reassuring.

"It's not a pure randomly assigned trial of rosiglitazone versus a different drug," Bach noted. "Our post-trial analysis compared patients treated with rosiglitazone to patients not receiving any TZD drug. That included patients in both arms – the insulin-providing and insulin-sensitizing arms," he says.