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CLINICAL STUDIES

The effects of moxonidine, a novel imidazoline, on plasma norepinephrine in patients with congestive heart failure

Karl Swedberg, MD, PhD, FACC^*, Claes-H.åkan Bergh, MD, PhD, Kenneth Dickstein, MD^c, John McNay, MD^{* c}, Mitchell Steinberg, MD, PhD Moxonidine Investigators

^* Department of Medicine, Sahlgrenska University Hospital/Östra, Göteborg, Sweden
Department of Cardiology, Sahlgrenska University Hospital/Sahlgrenska, Göteborg, Sweden
^c the Department of Cardiology, Central Hospital in Rogaland, Stavanger, Norway
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana, USA

Manuscript received June 3, 1999; revised manuscript received September 10, 1999, accepted October 25, 1999.

Reprint requests and correspondence: Dr. Karl Swedberg, Department of Medicine, Göteborg University, Sahlgrenska University Hospital/Östra, S-416 85 Göteborg, Sweden
Karl.Swedberg{at}hjl.gu.se

OBJECTIVE

To evaluate the dose response relationship of moxonidine on plasma concentration of norepinephrine during acute and chronic administration in patients with congestive heart failure (CHF).

BACKGROUND

Sympathetic activation is increased in heart failure. Moxonidine is an imidazoline ligand acting on the central nervous system (CNS) receptors to decrease sympathetic activation.

METHODS

Ninety-seven patients with heart failure and New York Heart Association class II–III symptoms and ejection fraction <40% were randomized to placebo or one of three target doses of moxonidine, 0.1, 0.2 or 0.3 mg administered twice daily. An initial dose of moxonidine 0.1 mg twice a day (b.i.d.) was followed by weekly increments of 0.1 mg b.i.d. until target dose. The second and third study days occurred after four weeks (at target dose) and after 12 weeks, respectively. At each study day, repeated blood samples were drawn.

RESULTS

There was a significant dose-related decrease of systolic blood pressure across all three study days. Heart rate decreased significantly on study day 3 in a dose-related manner. The acute 2 h decrease in plasma norepinephrine in response to all three doses of moxonidine was significantly different compared with placebo after four and 12 weeks. There was a significant linear relation between dose and plasma norepinephrine after four and 12 weeks in both 2 h peak and the time averaged effect (>8 h). The number of adverse events was similar in the moxonidine and placebo groups.

CONCLUSIONS

The increased sympathetic activation in CHF can be reduced by moxonidine through CNS inhibition.

Abbreviations and Acronyms   ACE = angiotensin converting enzyme   b.i.d. = twice a day   CHF = congestive heart failure   CNS = central nervous system   GLM = general linear model   HPLC = high performance liquid chromatography   NYHA = New York Heart Association   SD = standard deviation   SE = standard error of the mean

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