Older adults with diabetes treated with thiazolidinedione agents such as rosiglitazone have a significantly increased risk of myocardial infarction, congestive heart failure and death compared with peers who use other hypoglycemic drugs, according to an article in the December 12 issue of the Journal of the American Medical Association.

The thiazolidinediones rosiglitazone and pioglitazone are oral hypoglycemic agents used to treat type II diabetes. "While improved glycemic control has been linked to better clinical outcomes in diabetes and thiazolidinediones have been suggested as having potential cardiovascular benefits, recent concerns have arisen regarding adverse cardiac effects of these drugs," the authors wrote.

Some research has indicated that both rosiglitazone and pioglitazone may increase the risk of congestive heart failure and that rosiglitazone may be associated with an increased risk of myocardial infarction and death.

Lorraine L. Lipscombe, MD, MSc, of the Institute for Clinical Evaluative Sciences, Toronto, and colleagues evaluated the risks of heart failure, myocardial infarction, and all-cause death associated with the use of this drug class compared with other oral hypoglycemic agents among patients age 66 years or older with diabetes. This older patient population has often been under-represented in trials of these drugs, even though they have a high prevalence of diabetes and may be at greater risk of medication-related adverse effects.

The researchers analyzed data from health care databases in Ontario that included 159,026 individuals with diabetes who were treated with oral hypoglycemic agents and were followed for a median of 3.8 years. During this time, 7.9 percent had a hospital visit for congestive heart failure (12,491), 7.9 percent had a hospital visit for myocardial infarction (12,578), and 19 percent died (30,265).

Compared with people who used oral hypoglycemic agent combination therapy, current users of thiazolidinedione monotherapy had a 60 percent increased risk of congestive heart failure, a 40 percent increased risk of myocardial infarction, and a 29 percent increased risk of death. The increased risks appeared to be limited to rosiglitazone.

"Our findings argue against current labeling of thiazolidinediones that warns against use only in persons at high risk of congestive heart failure, as we did not identify any subgroup of older diabetes patients who may be protected from adverse effects of thiazolidinediones," the authors wrote. "These findings provide evidence from a real-world setting and support data from clinical trials that the harms of thiazolidinediones may outweigh their benefits, even in patients without obvious baseline cardiovascular disease."

"Further studies are needed to better quantify the risk-benefit tradeoffs associated with thiazolidinedione therapy and to explore whether the hazards associated with these agents are specific to rosiglitazone. In the interim, treatment decisions must remain individualized, with clinicians weighing the potential benefits and harms of thiazolidinedione treatment, especially among high-risk elderly populations."