TORONTO — A retrospective analysis has shown no adverse effects of thiazolidinediones on clinical outcomes in heart failure patients with diabetes.
In fact, thiazolidinedione (TZD) use was associated with reductions in all-cause hospitalizations, heart failure hospitalizations, and total hospital days. The reduction in hospital days also was noted in patients treated with TZD plus insulin.
These findings challenge current recommendations against the use of TZDs in heart failure that are based on concerns regarding fluid retention, particularly when used in combination with insulin. To date, there have been no trials assessing the impact of TZD therapy on heart failure outcomes.
“These findings support the concept that perhaps the nonhypoglycemic cardiovascular effects of TZDs may have favorable clinical impact in heart failure patients,” investigator John S. Golden, M.D., said during a poster presentation at the annual meeting of the Heart Failure Society of America.
Ultimately, clinical trials will determine the specific effects of TZDs in heart failure, and the extent to which an observational study can be extrapolated to a larger population.
“I can't tell you on the basis of this study that it is something we ought to be doing as a therapeutic intervention at this point,” said Dr. Golden of Mid-Atlantic Permanente Medical Group, Fairfax, Va. “I'm certainly not putting that much stock in hospital day reductions based on a small study like this. But, again, it lends some clinical support to the biochemical mechanisms supporting not only the safety, but efficacy, of TZDs in this population.”
Consecutively, 97 diabetic patients were referred to the heart failure treatment program at Mid-Atlantic with left ventricular ejection fractions of 35% or less and New York Heart Association (NYHA) class II-IV; 37% were treated with a TZD and 15% received a TZD plus insulin.
Patients treated with TZD and those not treated with the drug were well matched with regard to baseline left ventricular ejection fraction, glycosylated hemoglobin, and NYHA class. All patients were treated with ACE inhibitors or angiotensin receptor blockers, and 97% received β-blockers.
Clinical outcomes were measured at 1 year evaluating TZD use both alone and in combination with insulin.
Improvements in ejection fractions did not differ significantly between patients treated with TZDs and those who were not. Patients treated with a TZD, compared with those not treated, had significantly reduced all-cause hospitalizations per patient (0.19 vs. 0.71), heart failure hospitalizations per patient (0.03 vs. 0.16), and total hospital days (0.67 vs. 2.72), he said.
In the subpopulation treated with TZD plus insulin, there was a significant reduction in total hospital days per patient (0.07 vs. 2.30), compared with those not on the combination therapy. There was a trend toward increased diuretic usage in the TZD plus insulin group (69.3 mg vs. 45.5 mg furosemide/day). This was not seen in patients treated with TZD alone.