Clinical and autonomic effects of ibopamine as adjunct to angiotensin-converting enzyme inhibitors in chronic heart failure.
BACKGROUND
The purpose of this study was to determine the additive value of ibopamine in heart failure patients who are treated with angiotensin-converting enzyme inhibitors. Ibopamine exerts hemodynamic and neurohumoral effects, and is beneficial in mild heart failure; however, its additive value in more advanced disease in unclear.


RESULTS
The study was a stand-alone, double-blind, randomized parallel group comparison of ibopamine (100 mg 3 times daily) and placebo in 59 patients with New York Heart Association functional class III-IV heart failure. Patients were clinically stable on drug treatment, including an angiotensin-converting enzyme inhibitor, and they were randomized to ibopamine (n = 29) or placebo (n = 30). Assessments were performed at baseline and after 3 months of treatment, and included measurement of peak oxygen consumption, plasma neurohormones, ambulatory arrhythmias, and heart rate variability. At baseline, the two groups were well matched, including age (mean, 63 years), left ventricular ejection fraction (0.23), and peak oxygen consumption (15.4 mL/min/kg). After 3 months, four patients had dropped out of the study because of progressive heart failure (ibopamine, n = 1; placebo, n = 3; not significant) and two because of side effects (n = 1/1). Exercise time and peak oxygen consumption were not significantly affected (exercise time: ibopamine, +54 [95% confidence interval, -12, 120] seconds; placebo, +19 [-42, 81] seconds; peak oxygen consumption: ibopamine, +0.3 [-0.5, 1,2] mL/min/kg; placebo, +0.2 [-0.7, 1.0] mL/min/kg). Plasma neurohormones and ventricular arrhythmias during ambulatory monitoring were also unaffected. In contrast, heart rate variability parameters, in particular those associated with vagal tone (rMMSD, high-frequency power), significantly increased after 3 months on ibopamine (P = .01 vs placebo).


CONCLUSIONS
In this group of patients with clinically stable moderate to severe chronic heart failure, only a marginal and statistically nonsignificant effect on clinical parameters was observed after 3 months of treatment with ibopamine. Heart rate variability parameters, however, were significantly affected by ibopamine, despite the absence of an effect on plasma neurohormones.
Department of Cardiology/Thoraxcenter, University Hospital Groningen, The Netherlands.
B M
BM
Szabó
D J
DJ
van Veldhuisen
P H
PH
van der Burgh
J
J
Kruik
A R
AR
Girbes
K I
KI
Lie
D000368:Aged; D000450:Aldosterone / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology*; D001784:Blood Gas Analysis; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002908:Chronic Disease; D003846:Deoxyepinephrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015716:Electrocardiography, Ambulatory; D005080:Exercise Test; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D010101:Oxygen Consumption / Q000502:physiology; D011863:Radioimmunoassay; D012083:Renin / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D002316:Cardiotonic Agents; D000450:Aldosterone; C023487:ibopamine; D012083:Renin; D003846:Deoxyepinephrine; D009638:Norepinephrine