The effects of chronic, sustained-release moxonidine therapy on clinical and neurohumoral status in patients with heart failure

Aims: Congestive heart failure (CHF) is characterized by elevated plasma no repinephrine (PNE) associated with a poor prognosis. Moxonidine selectively stimulates medullary imidazoline receptors which centrally inhibit sympath etic outflow and potently suppress levels of circulating PNE. This study wa s designed to evaluate the effects of central sympathetic inhibition on cli nical and neurohumoral status in patients with CHF. Methods and results: Th is study evaluated 25 patients (age = 69 +/- 7 years, 20 males) with sympto matic CHF (NYHA II-III), stabilized on standard therapy. The mean ejection fraction was 28 +/- 7% at baseline. Patients were titrated in a double-blin d fashion to 11 weeks of oral therapy with placebo (n = 9) or sustained-rel ease (SR) moxonidine 0.9 mg bid (n = 16). Clinical and neurohumoral status were evaluated at baseline, on chronic therapy at the target dose, and duri ng cessation of therapy. All patients completed the trial and reached the t arget dose. Dry mouth, symptomatic hypotension, and asthenia were more freq uent in the moxonidine SR-treated group. PNE was substantially reduced afte r 6 weeks at the maximum dose (0.9 mg bid) by 50% vs, placebo (P < 0.0005). A reduction in 24-h mean heart rate (P < 0.01) was correlated to the reduc tion in PNE (r = 0.70, P < 0.05). A 36% increase in the standard deviation of normal-to-normal intervals (SDNN) was observed in the moxonidine SR grou p vs, a 2% decrease for placebo (P = 0.06); for the root mean square of suc cessive differences (rMSSD), there was a 21% increase for moxonidine SR vs. a 19% decrease for placebo (P < 0.05). Abrupt cessation of chronic therapy resulted in substantial increases in PNE, blood pressure, and heart rate. Conclusions: Chronic therapy with a sustained-release formulation of moxoni dine in patients with CHF was well tolerated, with substantial and sustaine d reductions in PNE. The tachyarrhythmias were attenuated, with evidence of improved autonomic tone. Due to the observed effects following moxonidine discontinuation, tapering of therapy is recommended. (C) 2000 Elsevier Scie nce Ireland Ltd. All rights reserved.