Issue 173 Item 5 Thiazolidinediones Linked to Heart Failure and Pulmonary Edema

Congestive heart failure and pulmonary edema are associated with pioglitazone and rosiglitazone treatment.

That, according to a review of the records of six men treated for type 2 diabetes. The authors therefore advise that thiazolidinediones be avoided in diabetics with left ventricular dysfunction or chronic renal insufficiency.

Drs. Asra Kermani and Abhimanyu Garg, of the University of Texas Southwestern Medical Center in Dallas, describe the six cases of new-onset congestive heart failure and pulmonary edema that followed initiation or dose increase of thiazolidinediones in the September 9th issue of the Mayo Clinic Proceedings. They point out that these cases represent 0.9% of patients treated over the past year at their facility with these insulin sensitizers.

Even though patients ranged in age from 66 to 78 years, none of them had any acute cardiac event that would otherwise explain their condition, the report indicates. Four had chronic renal insufficiency and one had ischemic cardiomyopathy. Symptoms resolved in each case within days of discontinuing thiazolidinediones and administration of diuretics.

"More and more, physicians are likely to use these agents because metformin is sometimes contraindicated," Dr. Garg told Reuters Health. "It appears to us that [it] may not be very prudent, because some of these same patients may be predisposed to this complication."

He noted that current prescribing information suggests pioglitazone and rosiglitazone should be avoided in patients with NYHA functional class III and IV cardiac status. "But now I think that these drugs should be contraindicated in patients with any evidence of heart failure."
He also recommends against their use in patients with any history of pulmonary edema, evidence of impaired left heart function, or elevated serum creatinine levels.

In an accompanying editorial, Dr. Frank P. Kennedy notes that "the most deleterious effect of thiazolidinediones on cardiac function is mediated via an increase in intravascular volume." There is "little evidence" of a direct negative effect on cardiac performance.
He also points that that these agents may in fact have beneficial effects on cardiac function, including diminished vascular resistance, improved metabolism, a positive inotropic effect and improved endothelial function.

"Because many patients with diabetes have asymptomatic cardiac dysfunction, it is reassuring that fluid retention, when it does occur with thiazolidinediones, appears to be manageable by dose withdrawal," adds Dr. Kennedy, a physician at the Mayo Clinic in Rochester, Minnesota.

Mayo Clin Proc 2003;78:1076-1077,1088-1091.