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CLINICAL RESEARCH: HEART FAILURE

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

Henry J. Dargie, MBChB^_*,_*, Per R. Hildebrandt, MD, Günter A.J. Riegger, MD, John J.V. McMurray, MD^_*, Stephen O. McMorn, PhD, Jeremy N. Roberts, MSc^||, Andrew Zambanini, MRCP and John P.H. Wilding, DM^¶

^_* Department of Cardiology, Western Infirmary, Glasgow, Scotland
Department of Cardiology, Frederiksberg Hospital, Fredriksberg, Denmark
Department of Cardiology, University of Regensberg, Regensberg, Germany
Cardiovascular and Metabolic Medicines Development Centre, GlaxoSmithKline, Harlow, England
^|| Biomedical Data Sciences, GlaxoSmithKline, Oakville, Canada
^¶ Clinical Sciences Centre, University Hospital Aintree, Liverpool, England.

Manuscript received November 11, 2005; revised manuscript received September 6, 2006, accepted October 12, 2006.

^_* Reprint requests and correspondence: Dr. Henry J. Dargie, Western Infirmary, CRI Department, Level 4, Glasgow, G11 6NT United Kingdom. (Email: H.Dargie{at}bio.gla.ac.uk).

Objectives: This study investigated the effects of rosiglitazone (RSG) on left ventricular ejection fraction (LVEF) in subjects with type 2 diabetes (T2DM) and pre-existing chronic heart failure (CHF) (New York Heart Association [NYHA] functional class I to II).

Background: Fluid retention is an important consideration in the use of thiazolidinediones in T2DM patients because it could exacerbate symptoms or precipitate decompensation in those with previously stable CHF.

Methods: A total of 224 patients with T2DM and NYHA functional class I to II CHF with LVEF 45% were randomized to a 52-week treatment with RSG (4 to 8 mg daily, n = 110) or placebo (PLB) (n = 114) in addition to background antidiabetes therapy. Treatment was uptitrated to achieve target fasting plasma glucose <126 mg/dl; CHF medications were adjusted as appropriate.

Results: The LVEF was similar in both groups at baseline (RSG 35.3 ± 6.2%, PLB 35.7 ± 7.8%) and after 52 weeks of treatment (mean difference 1.49%, p = 0.1). Glycemic control was significantly better in the RSG group (mean difference in hemoglobin A1c –0.65%, p < 0.0001). There were significantly more adjudicated events in the RSG group of new or worsening edema (RSG n = 28 [25.5%]; PLB n = 10 [8.8%]; p = 0.005) and increased CHF medication (RSG n = 36 [32.7%], PLB n = 20 [17.5%]; p = 0.037), but no significant difference between groups for other adjudicated end points. A similar proportion of patients withdrew from each treatment group because of adverse events.

Conclusions: After 52 weeks of treatment, RSG improved glycemic control but did not adversely affect LVEF in patients with T2DM and NYHA functional class I to II CHF. More fluid-related events occurred with RSG, although these generally did not lead to withdrawal from the study.

Abbreviations and Acronyms   BNP = brain natriuretic peptide   CHF = chronic heart failure   ECHO = echocardiogram/echocardiography   EE = efficacy evaluable   ITT = intent-to-treat with last observation carried forward   LVEDVI = left ventricular end-diastolic volume index   LVEF = left ventricular ejection fraction   LVESVI = left ventricular end-systolic volume index   LVMI = left ventricular mass index   NYHA = New York Heart Association   PLB = placebo   RSG = rosiglitazone   T2DM = type 2 diabetes mellitus

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