Rosiglitazone Does Not Adversely Affect Cardiac Function in Type 2 Diabetics With Heart Failure

April 16, 2007

April 16, 2007 (Glasgow, Scotland) – The use of rosiglitazone (Avandia, GlaxoSmithKline) in type 2 diabetic patients with NYHA class 1-2 heart failure does not adversely alter echocardiographic structure or function, according to the results of a recent study [1]. While there were more fluid-related events with the thiazolidinedione (TZD), these changes did not lead to study withdrawal and were not associated with a worsening of heart failure, report investigators.

"The primary objective of this study was to investigate the effects of rosiglitazone on cardiac structure and function in patients with type 2 diabetes mellitus and preexisting congestive heart failure," write Dr Henry Dargie (Western Infirmary, Glasgow, Scotland) and colleagues in the April 17, 2007 issue of the Journal of the American College of Cardiology. "The results show that the use of rosiglitazone over a period of one year was not associated with any significant changes in left ventricular volumes, left ventricular ejection fraction (LVEF), or cardiac index."

Fluid retention and edema are recognized side effects associated with TZDs. Because congestive heart failure is common in patients with type 2 diabetes, there has been concern that treatment with the drugs might lead to worsening of heart failure. The American Diabetes Association and the American Heart Association recently issued a consensus statement supporting the cautious use of TZDs in patients with NYHA class 1-2 heart failure but against use in patients with NYHA class 3-4 heart failure.

On the basis of this study, conclude Drs JoAnn Lindenfeld and Frederick Masoudi (University of Colorado, Denver), the authors of an editorial accompanying the published paper, "it seems unlikely that there is a clinically significant effect of TZDs on left ventricular systolic function" [2]. However, as they point out, the study does confirm worsening edema with the agents, an important clinical problem.

"Until better data emerge to guide the management of the fluid retention associated with TZDs, the recommendations of the AHA/ADA consensus committee about the use of TZDs in patients with heart failure remain relevant to the treatment of the increasing number of patients with diabetes mellitus and heart failure," write Lindenfeld and Masoudi.

Results presented at ADA scientific sessions in 2005

The study, previously presented at the American Diabetes Association 2005 Scientific Sessions by senior investigator Dr John Wilding (University Hospital Aintree, Liverpool, UK) and reported by heartwire at that time, included 224 patients with type 2 diabetes mellitus, an ejection fraction <45%, and a three-month history of NYHA class 1-2 congestive heart failure. All patients were treated with ACE-inhibitor or angiotensin-receptor-blocker therapy.

Patients were randomized to rosiglitazone 4 to 8 mg (n=110) or placebo (n=114) plus background antidiabetic agents for 52 weeks. At the end of the study, glycemic control was significantly better with rosiglitazone compared with placebo, with hemoglobin A1c (HbA1c) levels reduced 0.65% from baseline compared with no changes in HbA1c in the placebo-treated patients. However, in terms of the primary end point, there was no difference in LVEF change from baseline between the rosiglitazone-treated patients and those who received placebo. In addition, there was no significant difference in any left ventricular end diastolic and left ventricular end systolic volume indices.

The findings from this study confirm the results of previous studies, the editorialists comment, and "provide additional reassurance that the TZDs do not causes myocardial depression, even in patients with mild heart failure and systolic dysfunction."

Patients with other adjudicated clinical end points

Adjudicated end point Placebo, n=114 (%) Rosiglitazone, n=110 (%) p
New or worsening edema 8.8 25.5 0.005
Increase in congestive heart failure medication 17.5 32.7 0.037

Dargie and colleagues also report no increase in definite or possible worsening of clinical heart failure with rosiglitazone, although the number of episodes was small. There were, however, significantly more cases of new or worsening edema with rosiglitazone and significantly more patients treated with the TZD required an increase in heart-failure medications, most of which were increases in diuretics.

In their editorial, Lindenfeld and Masoudi write that patients with a history of heart failure will require careful monitoring when TZDs are initiated, and many of these will require either a decrease in dose or discontinuation or possibly an increase in diuretic medication. They note that it is not yet clear whether the potential detrimental effects of increased diuretic doses would counterbalance the potential benefits of TZDs on glycemia and cardiovascular risk factors.

  1. Dargie HJ, Hildebrandt PR, Riegger GA, et al. A randomized, placebo-controlled trial assessing the effects of rosiglitazone on echocardiographic function and cardiac status in type 2 diabetic patients with New York Heart Association functional class I or II heart failure. J Am Coll Cardiol 2007; 49:1696-704.

  2. Lindenfeld J, Masoudi FA. Fluid retention with thiazolidinediones. J Am Coll Cardiol 2007; 49:1705-07.

The complete contents of Heartwire , a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.

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