Hemodynamic and neuroendocrine effects for candoxatril and frusemide in mild stable chronic heart failure

• Published in: Journal of the American College of Cardiology Vol. 34; no. 6; pp. 1794 - 1801
• Main Authors: Westheim, Arne S., Bostrøm, Per, Christensen, Carl C., Parikka, Hanni, Rykke, Einar O., Toivonen, Lauri
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.11.1999; Elsevier Science
• Subjects: Adolescent; Adult; Aged; Aldosterone - blood; Antihypertensive Agents - pharmacology; Antihypertensive Agents - therapeutic use; Biological and medical sciences; Cardiotonic agents; Cardiovascular system; Chronic Disease; Diuretics - pharmacology; Diuretics - therapeutic use; Double-Blind Method; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Exercise Test; Furosemide - pharmacology; Heart Failure - drug therapy; Heart Failure - physiopathology; Hemodynamics - drug effects; Humans; Indans - pharmacology; Indans - therapeutic use; Medical sciences; Middle Aged; Neprilysin - antagonists & inhibitors; Pharmacology. Drug treatments; Propionates - pharmacology; Propionates - therapeutic use; Pulmonary Wedge Pressure - drug effects; Renin - blood; NYHA; ACE; ANP; CI; ECG; PCWP; LV; Human; Heart failure; Sulfanilamide derivatives; Sulfonamide; Enzyme; Treatment efficiency; Enzyme inhibitor; Cardiovascular disease; Atrial natriuretic peptide; Aldosterone; Furosemide; Diuretic; Peptidases; Chemotherapy; Chronic; Renin; Treatment; Heart disease; Candoxatril; Hydrolases; Aspartic endopeptidases; Hemodynamics
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/S0735-1097(99)00435-0

OBJECTIVES The study aimed to assess the hemodynamic and neuroendocrine effects of candoxatril and frusemide compared with placebo in patients with mild chronic heart failure. BACKGROUND Candoxatril is an atriopeptidase inhibitor. It increases circulating levels of atrial natriuretic peptide leading to natriuresis and diuresis, which alleviate the symptoms of a failing heart. METHODS This was a multicenter, randomized, double-blind study. Forty-seven patients with mild stable chronic heart failure received candoxatril 400 mg/day, frusemide 40 mg/day or placebo for up to six weeks. Cardiac indices were determined at rest and during exercise, and blood samples were taken for laboratory analysis. Assessments were performed at baseline (day 0) and after six weeks (day 42). RESULTS In comparison with placebo, both drugs significantly reduced mean pulmonary capillary wedge pressure following the first dose administration. Only candoxatril significantly reduced pulmonary capillary wedge pressure during exercise on day 0, while both drugs significantly reduced this parameter on day 42. Changes in the remaining hemodynamic parameters were comparable for both drugs relative to placebo. Frusemide significantly increased mean plasma renin activity (days 0 and 42), and the mean aldosterone concentration (day 42) in comparison with placebo, whereas candoxatril caused no significant changes in any of the hormonal parameters assessed. CONCLUSIONS These results show that candoxatril, 400 mg/day, has a similar hemodynamic profile to frusemide, 40 mg/day, but it does not induce adverse neuroendocrine effects. Candoxatril therefore appears to offer a clinically significant advantage over frusemide, providing an alternative therapeutic approach to the treatment of patients with mild stable chronic heart failure.