Author + information
- Received March 7, 1994
- Revision received January 5, 1995
- Accepted January 9, 1995
- Published online May 1, 1995.
- Joanna M. Good, MB, MRCPa,
- Michael Peters, MD, FRCRa,
- Martin Wilkins, MD, MRCPa,
- Neville Jackson, MD, MRCP*,
- Celia M. Oakley, MD, FRCP, FACC, FESCa and
- John G.F. Cleland, MD, FRCP, FESC, FACCa,1,†
- ↵†Present address and address for correspondence: Dr. John G. F. Cleland, Medical Research Council Clinical Research Initiative in Heart Failure, West Medical Building, University Avenue, Glasgow University, Glasgow, Scotland, United Kingdom G12 8QQ.
Objectives. Our primary objective was to compare the effects of three different doses of candoxatrilat with the effects of placebo on urinary volume in patients with moderately severe heart failure. The effects of candoxatrilat on urinary composition, neuroendocrine indexes and renal hemodynamic function were also studied.
Background. Candoxatrilat, a neutral endopeptidase inhibitor, reduces degradation of atrial natriuretic peptide and provokes diuresis in patients with mild heart failure, but the renal effects have not been studied in patients with moderately severe heart failure in a placebo-controlled study.
Methods. In a double-blind crossover trial, the effects of intravenous boluses of saline vehicle (placebo) and 50, 100 and 200 mg of candoxatrilat were compared on separate days in 12 patients with heart failure. Urinary output and composition were measured for 8 h. Renal blood flow and glomerular filtration rate were determined by radionuclide techniques. Blood was withdrawn for the measurement of hormones before and 3 h after dosing.
Results. All doses of candoxatrilat increased urinary volume (e.g., [mean ± SEM] 263 ± 53 to 490 ± 82 ml for saline solution and the 200-mg dose, respectively, p < 0.01) and sodium content (14 ± 4 to 37 ± 11 mmol, p < 0.001) in the 1st 4 h after dosing. Plasma atrial natriuretic peptide increased (140 ± 26 to 279 ± 37 pg/ml, p < 0.01), whereas aldosterone decreased (178 ± 41 to 125 ± 35 pg/ml, p < 0.01), and renin activity was unchanged (10 ± 2 to 12 ± 3 ng/ml per h).
Conclusions. Candoxatrilat given acutely causes diuresis, even in patients with moderately severe heart failure.
↵1 Dr. Cleland is supported by the British Heart Foundation, London.
Pfizer Central Research provided the trial medication and the financial support for Dr. Good.
- Received March 7, 1994.
- Revision received January 5, 1995.
- Accepted January 9, 1995.
- American College of Cardiology