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 alpha2 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.