Effects of chronic nitrate therapy on left-ventricular volume in patients with heart failure secondary to coronary disease already treated with captopril: a withdrawal study.
OBJECTIVE
This randomized, double-blind, placebo-controlled study with treatment lasting 16 weeks and withdrawal lasting 6 weeks tried to determine whether stopping nitrates has an effect on left-ventricular end-systolic volume in patients with heart failure who were chronically treated with captopril and diuretics.


METHODS
The study group comprised 29 patients with previous myocardial infarction, symptoms of mild-to-moderate heart failure, ejection fraction below 40%, no exercise-induced angina and no electrocardiographic signs of ischemia. After all patients had been treated with captopril (target dose: 25 mg twice daily), diuretics and the study drug (target dose: 40 mg isosorbide dinitrate twice daily or placebo) for 16 weeks, the study drug was withdrawn. The patients were then maintained on captopril and diuretics at constant doses for a 6-week withdrawal period. Radionuclide ventriculography with right-heart catheterization was performed at rest and during supine bicycle exercise after 16 weeks of double-blind treatment and at the end of the 6-week withdrawal period.


RESULTS
The changes in resting parameters following the withdrawal of the study drug were not different between the groups. At comparable maximum workload (placebo group 68 +/- 15 W, nitrate group 68 +/- 20 W), nitrate withdrawal caused a decrease in ejection fraction (placebo withdrawal: +0.8 +/- 4.0%; nitrate withdrawal: -2.7 +/- 4.3%, p < 0.02) and increases in left-ventricular end-diastolic volume (-9 +/- 35 vs. 23 +/- 48 ml, p < 0.02) and end-systolic volume (-9 +/- 33 vs. +24 +/- 47 ml; p < 0.01).


CONCLUSIONS
The addition of nitrates to a baseline therapy with captopril and diuretics might reduce exercise-induced left-ventricular dilatation in patients with heart failure from coronary disease.
Wieshammer
S
S
Department of Internal Medicine, University of Ulm, Germany.
Hetzel
M
M
Hetzel
J
J
Henze
E
E
Hombach
V
V
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002216:Captopril / Q000627:therapeutic use; D003327:Coronary Disease / Q000188:drug therapy* / Q000401:mortality; D004232:Diuretics / Q000627:therapeutic use; D004311:Double-Blind Method; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality; D013375:Substance Withdrawal Syndrome / Q000209:etiology; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D014665:Vasodilator Agents; D002216:Captopril; D007548:Isosorbide Dinitrate