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AIMS: To assess the effect of candoxatril, a novel neutral endopeptidase inhibitor, on exercise capacity, clinical status and quality of life in patients with mild to moderate chronic heart failure receiving angiotensin converting enzyme inhibition. METHODS AND RESULTS: Patients were recruited from 16 centres throughout the United Kingdom. Following a 4-week single-blind placebo 'run-in' phase of weekly exercise tests, patients underwent double-blind randomization to receive either candoxatril (100 mg twice daily) or placebo for the next 84 days. Patients were then reassessed every 28 days. Of 110 patients randomized, 56 received candoxatril and 54 placebo. Over the study period, the overall improvement in mean total exercise time in the candoxatril group in comparison to the placebo group was 34.1 s (P=0.02: 95% confidence interval: 5.1 to 63.0). There were no significant changes in functional class, clinical status or quality of life scores between the two groups. There was a trend for a small reduction in blood pressure in the candoxatril group. CONCLUSION: Candoxatril confers an improvement in exercise capacity in patients with chronic heart failure who are receiving maintenance angiotensin converting enzyme inhibitor therapy.

Original publication




Journal article


Eur heart j

Publication Date





1808 - 1813


Aged, Angiotensin-Converting Enzyme Inhibitors, Blood Pressure, Double-Blind Method, Exercise Test, Exercise Tolerance, Female, Heart Failure, Humans, Indans, Male, Middle Aged, Neprilysin, Propionates, Protease Inhibitors, Time Factors