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 |
|
Related Article
-
Fluid Retention With Thiazolidinediones: Does the Mechanism Influence the Outcome?
- JoAnn Lindenfeld and Frederick A. Masoudi
J. Am. Coll. Cardiol. 2007 49: 1705-1707.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
C. A. Bourg and B. B. Phillips
Rosiglitazone, Myocardial Ischemic Risk, and Recent Regulatory Actions
Ann. Pharmacother.,
February 1, 2012;
46(2):
282 - 289.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Boussageon, T. Bejan-Angoulvant, M. Saadatian-Elahi, S. Lafont, C. Bergeonneau, B. Kassai, S. Erpeldinger, J. M. Wright, F. Gueyffier, and C. Cornu
Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials
BMJ,
July 26, 2011;
343(jul26_1):
d4169 - d4169.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Goltsman, X. Wang, E. R. LaVallie, E. A. DiBlasio-Smith, E. Ovcharenko, A. Hoffman, Z. Abassi, G. Z. Feuerstein, and J. Winaver
Effects of Chronic Rosiglitazone Treatment on Renal Handling of Salt and Water in Rats With Volume-Overload Congestive Heart Failure
Circ Heart Fail,
May 1, 2011;
4(3):
345 - 354.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Singh, Y. K. Loke, and C. D. Furberg
Long-term use of thiazolidinediones and the associated risk of pneumonia or lower respiratory tract infection: systematic review and meta-analysis
Thorax,
May 1, 2011;
66(5):
383 - 388.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Home
Safety of PPAR Agonists
Diabetes Care,
May 1, 2011;
34(Supplement_2):
S215 - S219.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Jamieson
32 Diabetes mellitus
Oxford Textbook of Heart Failure,
January 1, 2011;
1(1):
med-9780199577729-chapter - med-9780199577729-chapter.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
D. K. McGuire, S. M. Abdullah, R. See, P. G. Snell, J. McGavock, L. S. Szczepaniak, C. R. Ayers, M. H. Drazner, A. Khera, and J. A. de Lemos
Randomized comparison of the effects of rosiglitazone vs. placebo on peak integrated cardiovascular performance, cardiac structure, and function
Eur. Heart J.,
September 2, 2010;
31(18):
2262 - 2270.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. MacDonald, D. T. Eurich, S. R. Majumdar, J. D. Lewsey, S. Bhagra, P. S. Jhund, M. C. Petrie, J. J. V. McMurray, J. R. Petrie, and F. A. McAlister
Treatment of Type 2 Diabetes and Outcomes in Patients With Heart Failure: A Nested Case-Control Study From the U.K. General Practice Research Database
Diabetes Care,
June 1, 2010;
33(6):
1213 - 1218.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Kaul, A. F. Bolger, D. Herrington, R. P. Giugliano, and R. H. Eckel
Thiazolidinedione Drugs and Cardiovascular Risks: A Science Advisory From the American Heart Association and American College of Cardiology Foundation
J. Am. Coll. Cardiol.,
April 27, 2010;
55(17):
1885 - 1894.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Kaul, A. F. Bolger, D. Herrington, R. P. Giugliano, and R. H. Eckel
Thiazolidinedione Drugs and Cardiovascular Risks: A Science Advisory From the American Heart Association and American College of Cardiology Foundation
Circulation,
April 27, 2010;
121(16):
1868 - 1877.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Komajda, J. J.V. McMurray, H. Beck-Nielsen, R. Gomis, M. Hanefeld, S. J. Pocock, P. S. Curtis, N. P. Jones, and P. D. Home
Heart failure events with rosiglitazone in type 2 diabetes: data from the RECORD clinical trial
Eur. Heart J.,
April 1, 2010;
31(7):
824 - 831.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. B. Horwich and G. C. Fonarow
Glucose, Obesity, Metabolic Syndrome, and Diabetes: Relevance to Incidence of Heart Failure
J. Am. Coll. Cardiol.,
January 26, 2010;
55(4):
283 - 293.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. T. Bloomgarden
The 6th Annual World Congress on the Insulin Resistance Syndrome
Diabetes Care,
October 1, 2009;
32(10):
e114 - e121.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. S. Chaggar, S. M. Shaw, and S. G. Williams
Review article: Thiazolidinediones and heart failure
Diabetes and Vascular Disease Research,
July 1, 2009;
6(3):
146 - 152.
[Abstract]
[PDF]
|
|
|
|
|
|
|
H Kaneda, T Shiono, Y Miyashita, S Takahashi, Y Taketani, H Domae, J Matsumi, S Mizuno, Y Minami, K Sugitatsu, et al.
Efficacy and safety of pioglitazone in patients with ST elevation myocardial infarction treated with primary stent implantation
Heart,
July 1, 2009;
95(13):
1079 - 1084.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K M Goode, J John, A S Rigby, E S Kilpatrick, S L Atkin, T Bragadeesh, A L Clark, and J G F Cleland
Elevated glycated haemoglobin is a strong predictor of mortality in patients with left ventricular systolic dysfunction who are not receiving treatment for diabetes mellitus
Heart,
June 1, 2009;
95(11):
917 - 923.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. K Mcguire, R. See, S. M Abdullah, P. G Snell, J. M Mcgavock, C. R Ayers, and L. S Szczepaniak
The effect of rosiglitazone on integrated cardiovascular performance, cardiac structure, function and myocardial triglyceride: trial design and rationale
Diabetes and Vascular Disease Research,
January 1, 2009;
6(1):
43 - 50.
[Abstract]
[PDF]
|
|
|
|
|
|
|
H. Von Bibra, M. Diamant, P. G Scheffer, T. Siegmund, and P.-M. Schumm-Draeger
Rosiglitazone, but not glimepiride, improves myocardial diastolic function in association with reduction in oxidative stress in type 2 diabetic patients without overt heart disease
Diabetes and Vascular Disease Research,
November 1, 2008;
5(4):
310 - 318.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. H Wu
Cardiotoxic drugs: clinical monitoring and decision making
Heart,
November 1, 2008;
94(11):
1503 - 1509.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Odom, B. Williamson, and L. Carter
Rosiglitazone and pioglitazone in the treatment of diabetes mellitus
Am. J. Health Syst. Pharm.,
October 1, 2008;
65(19):
1846 - 1850.
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Khanderia, R. Pop-Busui, and K. A Eagle
Thiazolidinediones in Type 2 Diabetes: A Cardiology Perspective
Ann. Pharmacother.,
October 1, 2008;
42(10):
1466 - 1474.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. MacDonald, M. C. Petrie, N. M. Hawkins, J. R. Petrie, M. Fisher, R. McKelvie, D. Aguilar, H. Krum, and J. J.V. McMurray
Diabetes, left ventricular systolic dysfunction, and chronic heart failure
Eur. Heart J.,
May 2, 2008;
29(10):
1224 - 1240.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
The DREAM Trial Investigators
Effects of Ramipril and Rosiglitazone on Cardiovascular and Renal Outcomes in People With Impaired Glucose Tolerance or Impaired Fasting Glucose: Results of the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial
Diabetes Care,
May 1, 2008;
31(5):
1007 - 1014.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Lingegowda
Review: evidence for major benefits and harms of antidiabetic agents for diabetes with heart failure is limited
Evid. Based Med.,
February 1, 2008;
13(1):
9 - 9.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. N. DeMaria, J. J. Bax, O. Ben-Yehuda, P. Clopton, G. K. Feld, G. S. Ginsburg, B. H. Greenberg, J. D. Knoke, W. Y.W. Lew, J. A.C. Lima, et al.
Highlights of the Year in JACC 2007
J. Am. Coll. Cardiol.,
January 29, 2008;
51(4):
490 - 512.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. K. McGuire and S. E. Inzucchi
New Drugs for the Treatment of Diabetes Mellitus: Part I: Thiazolidinediones and Their Evolving Cardiovascular Implications
Circulation,
January 22, 2008;
117(3):
440 - 449.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Erdmann and R. G. Wilcox
Weighing up the cardiovascular benefits of thiazolidinedione therapy: the impact of increased risk of heart failure
Eur. Heart J.,
January 1, 2008;
29(1):
12 - 20.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Stroup
Thiazolidinedione-induced edema in patients with heart failure
Am. J. Health Syst. Pharm.,
December 1, 2007;
64(23):
2426 - 2430.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Lewanczuk and P. W. Armstrong
Physiologic Straws in the Wind: In Which Direction Do They Bend?
J. Am. Coll. Cardiol.,
November 20, 2007;
50(21):
2059 - 2060.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. E. Gilbert
Rosiglitazone: Opening Pandora's Black Box?
Clin. J. Am. Soc. Nephrol.,
November 1, 2007;
2(6):
1329 - 1331.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Singh, Y. K. Loke, and C. D. Furberg
Long-term Risk of Cardiovascular Events With Rosiglitazone: A Meta-analysis
JAMA,
September 12, 2007;
298(10):
1189 - 1195.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Ashrafian, M. P. Frenneaux, and L. H. Opie
Metabolic Mechanisms in Heart Failure
Circulation,
July 24, 2007;
116(4):
434 - 448.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Lindenfeld and F. A. Masoudi
Fluid Retention With Thiazolidinediones: Does the Mechanism Influence the Outcome?
J. Am. Coll. Cardiol.,
April 24, 2007;
49(16):
1705 - 1707.
[Full Text]
[PDF]
|
|
|
|
