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CLINICAL STUDIES

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

Arne S. Westheim, MD, PhD^*, Per Bostrøm, MD, Carl C. Christensen, MD^*, Hanni Parikka, MD, Einar O. Rykke, MD^* and Lauri Toivonen, MD

^* Department of Cardiology, Ullevál Hospital, Oslo, Norway
Södra Skolgatan 31, Malmö, Sweden
Division of Cardiology, Helsinki University Hospital, Helsinki, Finland

Manuscript received October 15, 1999; revised manuscript received June 17, 1999, accepted August 18, 1999.

Reprint requests and correspondence: Dr. Arne S. Westheim, Department of Cardiology, Ullevál Hospital, 0407 Oslo, Norway

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.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   ANP = atrial natriuretic peptide   CI = cardiac index   ECG = electrocardiogram   LV = left ventricular   NYHA = New York Heart Association   PCWP = pulmonary capillary wedge pressure

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