Placebo-controlled comparison of candoxatril, an orally active neutral endopeptidase inhibitor, and captopril in patients with chronic heart failure.
OBJECTIVE
To compare the effects on exercise capacity of the neutral endopeptidase inhibitor candoxatril, and the angiotensin converting enzyme inhibitor captopril, in patients with mild to moderate heart failure.


METHODS
In this multi-centre double-blind placebo controlled study, 60 patients with NYHA Class I-III heart failure were randomised to candoxatril 200 mg b.d. (n = 22), captopril 25-50 mg b.d. (n = 23) or placebo (n = 15). Treadmill exercise tests were carried out weekly during a 5-week single-blind placebo run-in phase until a stable baseline was achieved, and repeated at 4 weekly intervals during the 12-week double-blind treatment phase.


RESULTS
Nine patients withdrew from the study--four candoxatril and five captopril. The placebo-adjusted increase in exercise duration after 12 weeks was 56 s (95% CI, -26 to +137 s; P = 0.12) with candoxatril and 37 s (-43 to + 117 s; P = 0.29) with captopril.


CONCLUSIONS
Both candoxatril and captopril were well tolerated and treadmill exercise duration appeared to increase during 12 weeks of therapy but this did not achieve statistical significance. This study tentatively suggests that in patients with heart failure, neutral endopeptidase inhibition may provide similar symptomatic benefits to angiotensin converting enzyme inhibition.
Northridge
D B
DB
Department of Cardiology, Western General Hospital, Edinburgh, UK.
Currie
P F
PF
Newby
D E
DE
McMurray
J J
JJ
Ford
M
M
Boon
N A
NA
Dargie
H J
HJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D002216:Captopril / Q000494:pharmacology* / Q000627:therapeutic use; D004311:Double-Blind Method; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D007189:Indans / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011422:Propionates / Q000494:pharmacology* / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D007189:Indans; D011422:Propionates; D011480:Protease Inhibitors; D002216:Captopril; C062766:candoxatril