Acute hemodynamic and neurohumoral effects of moxonidine in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

Elevated plasma norepinephrine (PNE) has been shown to be an important pred ictor of morbidity and mortality in patients with congestive heart failure (CHF). Moxonidine selectively stimulates imidazoline receptors located in t he medulla, which centrally inhibit sympathetic outflow. PNE is suppressed and peripheral vasodilation reduces systemic blood pressure. This study eva luated the acute neurohumoral and hemodynamic effects of a single dose of o ral moxonidine in 32 patients (22 men, mean +/- SD age 66 +/- 10 years) wit h CHF. All patients were in New York Heart Association functional class III and stabilized on chronic therapy with diuretics, digitalis, and angiotens in-converting enzyme inhibitors. The mean PNE concentration was 509 +/- 304 pg/ml at baseline. Patients underwent invasive hemodynamic monitoring afte r double-blind randomization to either placebo (n = 12), moxonidine 0.4 mg (n = 9), or moxonidine 0.6 mg (n = 11). Moxonidine produced a dose-dependen t, vasodilator response compared with placebo. Analysis of the rime-average d change from baseline over 6 hours demonstrated that moxonidine 0.6 mg cau sed significant reductions in mean systemic arterial pressure (p < 0.0001), mean pulmonary arterial pressure (p < 0.005), systemic vascular resistance (p < 0.05), pulmonary vascular resistance (p < 0.01), and heart rate (p < 0.05). Stroke volume was unchanged. PNE was reduced substantially (-180 pg/ ml at 4 hours, p < 0.005) and the reduction was highly correlated with the baseline level (r = -0.968). Moxonidine was well tolerated in this single-d ose study and resulted in a modest, dose-dependent, vasodilator response, w ith substantial reductions in systemic and pulmonary arterial blood pressur e, Trials designed to evaluate the clinical efficacy of chronic moxonidine therapy in CHF added to conventional therapy would be appropriate. (C) 1999 by Excerpta Medica, Inc.