LACK OF EFFECT OF NITRATES ON EXERCISE TOLERANCE IN PATIENTS WITH MILD-TO-MODERATE HEART-FAILURE CAUSED BY CORONARY-DISEASE ALREADY TREATEDWITH CAPTOPRIL

Objective-To test the hypothesis that the addition of nitrates improve s exercise tolerance in patients with heart failure caused by coronary artery disease already treated with an angiotensin converting enzyme inhibitor and diuretics.Design-Randomised, double blind, placebo contr olled, 16 week treatment periods. Setting-Outpatient clinic at a unive rsity hospital. Patients-54 patients with previous myocardial infarcti on, symptoms of mild to moderate heart failure, left ventricular eject ion fraction below 40%, no exercise-induced angina or electrocardiogra phic signs of ischaemia. Four patients in the nitrate group (n = 24) a nd one patient of the placebo group (n = 25) were withdrawn from the s tudy. Intervention-After the patients had been on constant doses of ca ptopril and diuretics for at least 2 weeks, they were randomised to re ceive a target dose of 40 mg isosorbide dinitrate twice daily or place bo in addition to the continuation of captopril and diuretics. Measure ments-Bicycle exercise tests with measurement of gas exchange were car ried 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. Resu lts-The increase in peak oxygen uptake from before randomisation tende d 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. Conclusion-The addition of nitrates to a baseline treat ment consisting of captopril and diuretics did not improve exercise to lerance.