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Hemodynamic and neuroendocrine effects for candoxatril and frusemide in mild stable chronic heart failure
A S Westheim1, P Bostrøm, C C Christensen
1Department of Cardiology, Ullevál Hospital, Oslo, Norway.
Insights
Candoxatril and frusemide improved hemodynamics in chronic heart failure. Candoxatril offers a similar hemodynamic benefit to frusemide without adverse neuroendocrine effects, presenting a potential alternative therapy.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Candoxatril is an atriopeptidase inhibitor that elevates atrial natriuretic peptide levels.
- This elevation promotes natriuresis and diuresis, aiding in the management of heart failure symptoms.
Purpose of the Study:
- To compare the hemodynamic and neuroendocrine effects of candoxatril and frusemide against a placebo in patients with mild chronic heart failure.
Main Methods:
- A multicenter, randomized, double-blind study involving 47 patients with mild stable chronic heart failure.
- Patients received candoxatril (400 mg/day), frusemide (40 mg/day), or placebo for six weeks.
- Hemodynamic parameters were assessed at rest and during exercise at baseline and after six weeks.
Main Results:
- Both candoxatril and frusemide significantly reduced pulmonary capillary wedge pressure compared to placebo after the first dose.
- Candoxatril uniquely reduced pulmonary capillary wedge pressure during exercise on day 0.
- Frusemide increased plasma renin activity and aldosterone, while candoxatril did not alter these neuroendocrine markers.
Conclusions:
- Candoxatril (400 mg/day) demonstrates a hemodynamic profile comparable to frusemide (40 mg/day) in mild chronic heart failure.
- Unlike frusemide, candoxatril does not induce adverse neuroendocrine effects.
- Candoxatril presents a promising alternative therapeutic option for patients with mild stable chronic heart failure.
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.