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

OBJECTIVE To evaluate the dose response relationship of moxonidine on plasm a concentration of norepinephrine during acute and chronic administration i n 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) recept ors to decrease sympathetic activation. METHODS Ninety-seven patients with heart failure and New York Heart Associa tion class II-III symptoms and ejection fraction <40% were randomized to pl acebo or one of three target doses of moxonidine, 0.1, 0.2 or 0.3 mg admini stered 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. Th e second and third study days occurred after four weeks (at target dose) an d after 12 weeks, respectively. At each study day, repeated blood samples w ere drawn. RESULTS There was a significant dose-related decrease of systolic blood pre ssure across all three study days. Heart rate decreased significantly on st udy day 3 in a dose-related manner. The acute 2 h decrease in plasma norepi nephrine in response to all three doses of moxonidine was significantly dif ferent compared with placebo after four and 12 weeks. There was a significa nt 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 m oxonidine through CNS inhibition. (J Am Coll Cardiol 2000;35:398-404) (C) 2 000 by the American College of Cardiology.