Double-blind placebo-controlled study of ibopamine and digoxin in patients with mild to moderate heart failure: results of the Dutch Ibopamine Multicenter Trial (DIMT)

Department of Cardiology/Thoraxcenter, University Hospital, Groningen, The Netherlands.

OBJECTIVES. This study was conducted to determine the efficacy and safety of long-term treatment with the orally active dopamine agonist ibopamine in patients with mild to moderate chronic congestive heart failure and to compare the results with those of treatment with digoxin and placebo. BACKGROUND. Ibopamine and digoxin are drugs that exert hemodynamic and neurohumoral effects. Because there is accumulating evidence that progression of disease in chronic heart failure is related not only to hemodynamic but also to neurohumoral factors, both drugs might be expected to have a favorable long-term effect. METHODS. We studied 161 patients with mild to moderate chronic heart failure (80% in New York Heart Association functional class II and 20% in class III), who were treated with ibopamine (n = 53), digoxin (n = 55) or placebo (n = 53) for 6 months. Background therapy consisted of furosemide (0 to 80 mg); all other drugs for heart failure were excluded. Clinical assessments were made at baseline and after 1, 3 and 6 months. RESULTS. Of the 161 patients, 128 (80%) completed the study. Compared with placebo, digoxin but not ibopamine significantly increased exercise time after 6 months (p = 0.008 by intention to treat analysis). Ibopamine was only effective in patients with relatively preserved left ventricular function, as it significantly increased exercise time in this subgroup (for patients with a left ventricular ejection fraction > 0.30; p = 0.018 vs. placebo). No patient receiving digoxin withdrew from the study because of progression of heart failure, compared with six patients receiving ibopamine and two receiving placebo. At 6 months, plasma norepinephrine was decreased with digoxin and ibopamine therapy (-106 and -13 pg/ml, respectively) but increased with placebo administration (+62 pg/ml) (both p < 0.05 vs. placebo). Plasma aldosterone was unaffected, but renin was decreased by both agents after 6 months (p < 0.05 vs. placebo). Total mortality and ambulatory arrhythmias were not significantly affected by the two drugs. CONCLUSIONS. Ibopamine and digoxin both inhibit neurohumoral activation in patients with mild to moderate chronic heart failure. However, the clinical effects of these drugs are different and appear to be related to the degree of left ventricular dysfunction.

This article has been cited by other articles:

				S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, D. M. Mancini, K. Michl, et al. 2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation J. Am. Coll. Cardiol., April 14, 2009; 53(15): e1 - e90. [Full Text] [PDF]

				M. Jessup, W. T. Abraham, D. E. Casey, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. A. Konstam, D. M. Mancini, P. S. Rahko, M. A. Silver, et al. 2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation J. Am. Coll. Cardiol., April 14, 2009; 53(15): 1343 - 1382. [Full Text] [PDF]

				2009 WRITING GROUP TO REVIEW NEW EVIDENCE AND UPDA, M. Jessup, W. T. Abraham, D. E. Casey, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. A. Konstam, D. M. Mancini, P. S. Rahko, et al. 2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in Collaboration With the International Society for Heart and Lung Transplantation Circulation, April 14, 2009; 119(14): 1977 - 2016. [Full Text] [PDF]

				2005 WRITING COMMITTEE MEMBERS, S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, D. M. Mancini, et al. 2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in Collaboration With the International Society for Heart and Lung Transplantation Circulation, April 14, 2009; 119(14): e391 - e479. [Full Text] [PDF]

				A. Ahmed Digoxin and Reduction in Mortality and Hospitalization in Geriatric Heart Failure: Importance of Low Doses and Low Serum Concentrations J Gerontol A Biol Sci Med Sci, March 1, 2007; 62(3): 323 - 329. [Abstract] [Full Text] [PDF]

				S. H. Rahimtoola Digitalis Therapy for Patients in Clinical Heart Failure Circulation, June 22, 2004; 109(24): 2942 - 2946. [Full Text] [PDF]

				M. Gheorghiade, K. F. Adams Jr, and W. S. Colucci Digoxin in the Management of Cardiovascular Disorders Circulation, June 22, 2004; 109(24): 2959 - 2964. [Full Text] [PDF]

				S. S. Rathore, J. P. Curtis, Y. Wang, M. R. Bristow, and H. M. Krumholz Association of Serum Digoxin Concentration and Outcomes in Patients With Heart Failure JAMA, February 19, 2003; 289(7): 871 - 878. [Abstract] [Full Text] [PDF]

				K. F. Adams Jr, M. Gheorghiade, B. F. Uretsky, J. H. Patterson, T. A. Schwartz, and J. B. Young Clinical benefits of low serum digoxin concentrations in heart failure J. Am. Coll. Cardiol., March 20, 2002; 39(6): 946 - 953. [Abstract] [Full Text] [PDF]

				D. J. van Veldhuisen, S. Genth-Zotz, J. Brouwer, F. Boomsma, T. Netzer, A. J. Man in 't Veld, Y. M. Pinto, K. I. Lie, and H. J. G. M. Crijns High- versus low-dose ACE inhibition in chronic heart failure: A double-blind, placebo-controlled study of imidapril J. Am. Coll. Cardiol., December 1, 1998; 32(7): 1811 - 1818. [Abstract] [Full Text] [PDF]

				M. Gheorghiade and R. O. Bonow Chronic Heart Failure in the United States : A Manifestation of Coronary Artery Disease Circulation, January 27, 1998; 97(3): 282 - 289. [Full Text] [PDF]

				M. Gheorghiade, V. B. Hall, G. Jacobsen, M. Alam, H. Rosman, and S. Goldstein Effects of Increasing Maintenance Dose of Digoxin on Left Ventricular Function and Neurohormones in Patients With Chronic Heart Failure Treated With Diuretics and Angiotensin-Converting Enzyme Inhibitors Circulation, October 1, 1995; 92(7): 1801 - 1807. [Abstract] [Full Text]