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Rosiglitazone in Diabetic Patients With Heart Failure - Rosiglitazone in Diabetic Patients With Heart Failure
Description:
The goal of the trial was to evaluate the effect of rosiglitazone on left ventricular ejection fraction (LVEF) among patients with type 2 diabetes and pre-existing chronic heart failure (CHF).
Hypothesis:
Rosiglitazone will be noninferior to placebo with respect to change from baseline to week 52 in LVEF.
Study Design
Study Design:
Patients Enrolled: 224
Mean Follow Up: One year
Mean Patient Age: Mean age, 64 years
Female: 18
Patient Populations:
Type 2 diabetes and mild to moderate stable CHF (NYHA functional class I-II), inadequate glycemic control at screening (fasting plasma glucose ≥126 mg/dl and ≤216 mg/dl), treated with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and LVEF ≤45%
Exclusions:
Body mass index >35 kg/m2, creatinine clearance <40 ml/min, significant hepatic disease, laboratory-confirmed anemia, receiving any antidiabetes treatment except for a thiazolidinedione, insulin, or combination therapy with an insulin secretagogue and acarbose
Primary Endpoints:
Change from baseline to week 52 in LVEF, evaluated for noninferiority
Drug/Procedures Used:
Following a 4-week run-in period on placebo, patients were randomized in a double-blind manner to rosiglitazone (4-8 mg/d; n = 110) or placebo (n = 114). Treatment was to continue for 52 weeks. All patients also received background standard antidiabetic and HF therapy.
Principal Findings:
At baseline, mean LVEF was approximately 35% in both groups. New York Heart Association (NYHA) class II was present in 59% of patients. Mean HbA1c was 7.8% and mean fasting plasma glucose was 163 mg/dl.
The primary endpoint of change in LVEF was noninferior for the comparison of rosiglitazone with placebo (adjusted mean difference from placebo at 52 weeks 1.49%, 95% confidence interval, -0.32 to 3.30, p = 0.1). The absolute change from baseline in LVEF was 2.5% in the rosiglitazone group and 1.1% in the placebo group.
Change in other echocardiographic measures was also similar between groups, including LV end-diastolic volume index, LV end-systolic volume index, LV mass index, and cardiac index. Glycemic control at 52 weeks as assessed by HbA1c was significantly better in the rosiglitazone group compared with placebo (mean difference in HbA1c 0.65%, p < 0.0001). Increase in weight at 52 weeks was greater in the rosiglitazone group (+1.3 kg) than in the placebo group (-0.3 kg).
Among the clinical events, new or worsening edema occurred more frequently in the rosiglitazone group (25.5% vs. 8.8%, p = 0.005) as did need for an increase in CHF medication (32.7 vs. 17.5%, p = 0.037). There was no significant difference in cardiovascular hospitalization (19.1% vs. 13.2%, p = 0.47) or definite or possible worsening of CHF. Death occurred in 7.7% of the rosiglitazone group and 4.8% of the placebo group (p = 0.48).
Interpretation:
Among patients with type 2 diabetes and pre-existing CHF, treatment with rosiglitazone was noninferior to placebo for the effect on change in LVEF at 52 weeks.
While there was no change in LVEF or other echocardiographic parameters, the clinical event of new or worsening edema was increased in the rosiglitazone group. Additionally, increase in weight was greater with rosiglitazone. Conversely, glycemic control was better with rosiglitazone.
Thiazolidinediones have previously been shown to be associated with increased edema in other trials. While most of the excess in edema in the present study was able to be managed with diuretics in the present trial and did not lead to an increase in study withdraw, the authors note that patients with impaired CHF who are treated with rosiglitazone should be closely monitored for worsening symptoms of CHF.
References:
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.
Keywords: Blood Glucose, Diabetes Mellitus, Type 2, Diuretics, Heart Failure, Stroke Volume, Edema, Hypoglycemic Agents, Confidence Intervals, Hospitalization, Fasting, Thiazolidinediones
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