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 tre atment lasting 16 weeks and withdrawal lasting 6 weeks tried to determine w hether stopping nitrates has an effect on left-ventricular end-systolic vol ume in patients with heart failure who were chronically treated with captop ril and diuretics. Patients and Methods: The study group comprised 29 patie nts with previous myocardial infarction, symptoms of mild-to-moderate heart failure, ejection fraction below 40%, no exercise-induced angina and no el ectrocardiographic signs of ischemia. After all patients had been treated w ith captopril (target dose: 25 mg twice daily), diuretics and the study dru g (target dose: 40 mg isosorbide dinitrate twice daily or placebo) for 16 w eeks, the study drug was withdrawn. The patients were then maintained on ca ptopril and diuretics at constant doses for a 6-week withdrawal period. Rad ionuclide ventriculography with right-heart catheterization was performed a t rest and during supine bicycle exercise after 16 weeks of double-blind tr eatment and at the end of the 6-week withdrawal peri od. Results: The chang es in resting parameters fo I towing the withdrawal of the study drug were not different between the groups. At comparable maximum workload (placebo g roup 68 +/- 15 W, nitrate group 68 +/- 20 W), nitrate withdrawal caused a d ecrease in ejection fraction (placebo withdrawal: +0.8 +/- 4.0%; nitrate wi thdrawal: -2.7 +/- 4.3%, p < 0.02) and increases in left-ventricular end-di astolic volume (-9 +/- 35 vs. 23 +/- 48 ml, p < 0.02) and end-systolic volu me (-9 +/- 33 vs. +24 +/- 47 ml, p < 0.01). Conclusion: The addition of nit rates to a baseline therapy with captopril and diuretics might reduce exerc ise-induced left-ventricular dilatation in patients with heart failure from coronary disease. Copyright (C) 2001 S. Karger AG. Basel.