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

Abstract

Dopamine agonists have been studied in chronic heart failure, but earlier reports with non-selective compounds demonstrated unfavourable long-term effects. CHF 1035 is an orally active, new selective dopamine agonist, primarily activating DA₂ ⁻ and α₂ receptors, thereby inhibiting norepinephrine release, which may be beneficial in heart failure. We conducted a double-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 (left ventricular ejection fraction <0.45). Patients were clinically stable on diuretics and angiotensin converting enzyme inhibitors. Both acute and chronic assessments were made, including plasma neurohormones and 24-hr Holter monitoring for heart rate variability analysis. CHF1035 was generally well tolerated during the study. After 10 days, there were no significant changes between the groups regarding heart rate and blood pressure. Compared to placebo, plasma norepinephrine levels decreased on CHF1035, both in the first 4 hours and after 10 days (p < 0.05 between groups). Other neurohormones (natriuretic peptides, renin, aldosteron and endothelin) were not significantly affected. Heart rate variability parameters generally increased on CHF1035, but were unaffected by placebo (p < 0.05 between groups). Short-term treatment with the selective dopaminergic agonist CHF1035 is well tolerated, reduces plasma norepinephrine concentrations and increases heart rate variability in mild chronic heart failure.