Thiazolidinediones and Heart Disease Risk

Pioglitazone had a mixed risk profile, and rosiglitazone increased risk for ischemic heart disease, but neither increased mortality.

Results from small clinical trials and early pooled analyses have raised concerns about cardiovascular risks associated with rosiglitazone, one of two thiazolidinediones used to treat patients with type 2 diabetes mellitus. Two new meta-analyses further clarify the risks associated with pioglitazone and rosiglitazone.

Independent researchers analyzed data provided by the manufacturer from 19 randomized trials (16,390 patients) that compared pioglitazone with placebo or an active comparator. Most treatment protocols were 12 to 24 months. The hazard ratios for myocardial infarction, stroke, or death each were reduced after about 1 year of treatment with pioglitazone, although only the 18% reduction in the combined endpoint was significant. Risk for serious heart failure was significantly increased by 41%.

In a review of 140 randomized trials, researchers found 4 trials (14,291 patients) that compared rosiglitazone with placebo or an active comparator and had at least 12 months of follow-up. The risk for myocardial infarction in patients who received rosiglitazone was increased by about 40%, and the risk for heart failure was more than doubled; however, the risk for death from cardiovascular disease was not increased.

Comment: Both thiazolidinediones are associated with increased risk for heart failure in patients with type 2 diabetes mellitus, but only rosiglitazone appears to increase risk for ischemic heart disease. Prescribing information for both drugs now includes a "black box" warning about heart failure; in addition, an FDA advisory committee has suggested that warnings about ischemic heart disease be included for rosiglitazone. Editorialists note how unlikely it would have been for either drug to have been approved initially had these risks been known. They call for tighter postmarketing surveillance, especially for new classes of drugs and in higher-risk patients.

— Thomas L. Schwenk, MD