Autonomic and hemodynamic effects of a new selective dopamine agonist, CHF1035, in patients with chronic heart failure

Dopamine agonists have been studied in chronic heart failure, but earlier r eports with non-selective compounds demonstrated unfavourable long-term eff ects. CHF 1035 is an orally active, new selective dopamine agonist, primari ly activating DA(2)- and alpha (2) receptors, thereby inhibiting norepineph rine release, which may be beneficial in heart failure. We conducted a doub le-blind, placebo-controlled comparison of CHF 1035 (10 mg/day, n = 20) and placebo (n = 9) in patients with mild to moderate chronic heart failure (l eft ventricular ejection fraction <0.45). Patients were clinically stable o n diuretics and angiotensin converting enzyme inhibitors. Both acute and ch ronic assessments were made, including plasma neurohormones and 24-hr Holte r monitoring for heart rate variability analysis. CHF1035 was generally wel l tolerated during the study. After 10 days, there were no significant chan ges between the groups regarding heart rate and blood pressure. Compared to placebo, plasma norepinephrine levels decrease on CHF1035, both in the fir st 4 hours and after 10 days (p < 0.05 between groups). Other neurohormones (natriuretic peptides, renin, aldosteron and endothelin) were not signific antly affected. Heart rate variability parameters generally increased on CH F1035, but were unaffected by placebo (p < 0.05 between groups). Short-term treatment with the selective dopaminergic agonist CHF1035 is well tolerate d, reduces plasma norepinephrine concentrations and increases heart rate va riability in mild chronic heart failure.