Lack of effect of nitrates on exercise tolerance in patients with mild to moderate heart failure caused by coronary disease already treated with captopril.
OBJECTIVE
To test the hypothesis that the addition of nitrates improves exercise tolerance in patients with heart failure caused by coronary artery disease already treated with an angiotensin converting enzyme inhibitor and diuretics.


METHODS
Randomised, double blind, placebo controlled, 16 week treatment periods.


METHODS
Outpatient clinic at a university hospital.


METHODS
54 patients with previous myocardial infarction, symptoms of mild to moderate heart failure, left ventricular ejection fraction below 40%, no exercise-induced angina or electrocardiographic signs of ischaemia. Four patients in the nitrate group (n = 24) and one patient of the placebo group (n = 25) were withdrawn from the study.


METHODS
After the patients had been on constant doses of captopril and diuretics for at least 2 weeks, they were randomised to receive a target dose of 40 mg isosorbide dinitrate twice daily or placebo in addition to the continuation of captopril and diuretics.


METHODS
Bicycle exercise tests with measurement of gas exchange were carried out before randomisation and after 1, 6, 12, and 16 weeks of the double blind treatment. The change in peak oxygen uptake from control to week 16 was prospectively defined as the main outcome measure.


RESULTS
The increase in peak oxygen uptake from before randomisation tended to be greater in the placebo group (before randomisation 17.4 (3.4) ml/min/kg) than in the nitrate group (before randomisation 17.1 (3.5) ml/min/kg) after 12 weeks (mean increase 1.1 (2.7) v 0.0 (2.7) ml/min/kg, p < 0.12) and 16 weeks (1.7 (3.0) v 0.3 (2.6) ml/min/kg, p < 0.14) of treatment.


CONCLUSIONS
The addition of nitrates to a baseline treatment consisting of captopril and diuretics did not improve exercise tolerance.
Department of Cardiology, University of Ulm, Germany.
S
S
Wieshammer
M
M
Hetzel
J
J
Hetzel
M
M
Kochs
V
V
Hombach
D000328:Adult; D000368:Aged; D001794:Blood Pressure; D002216:Captopril / Q000627:therapeutic use*; D002303:Cardiac Output, Low / Q000209:etiology / Q000503:physiopathology*; D003327:Coronary Disease / Q000150:complications / Q000188:drug therapy*; D004232:Diuretics / Q000627:therapeutic use; D004311:Double-Blind Method; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D006339:Heart Rate; D006801:Humans; D007548:Isosorbide Dinitrate / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011659:Pulmonary Gas Exchange
D004232:Diuretics; D002216:Captopril; D007548:Isosorbide Dinitrate