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

Abstract

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. Patients and 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and the study drug (target dose: 40 mg isosorbide dinitrate twice daily or placebo) for 16 weeks, the study drug was withdrawn.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). Conclusion: 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.