Effect of isosorbide-5-mononitrate on exercise performance and clinical status in patients with congestive heart failure. Results of the Nitrates in Congestive Heart Failure (NICE) Study.

BACKGROUND AND AIMS: Nitrate therapy improves hemodynamics in patients with heart failure, but the chronic effects of oral nitrates on exercise performance and clinical status have not been well studied.

METHODS

Oral isosorbide-5-mononitrate (ISMN) (50 mg once daily) or placebo was administered to 136 patients (NYHA Class 2-3) treated for heart failure, all receiving captopril and most also furosemide. Endpoints were treadmill exercise time at 12 weeks by modified Naughton protocol (primary), with an additional 12-week follow-up period. Secondary endpoints included left ventricular dimensions, ejection fraction, cardiothoracic ratio, functional class, quality of life, hospitalizations and plasma norepinephrine and atrial natriuretic peptide in a four-center substudy.

RESULTS

Intention-to-treat analysis showed that mean change in treadmill exercise duration tended to be greater in patients receiving ISMN than placebo (treatment difference +42 s, 95% CI -5, +90 s at 12 weeks and +21 s, 95% CI -25, +74 s after 24 weeks) (NS). Treatment difference was greater in the prespecified subgroup with ejection fraction 31-40% (+55 s, 95% CI -11, +136 s at 12 weeks and +65 s, 95% CI +3, +147 s) (p = 0.035) at 24 weeks. No deleterious effects (i.e. hypotension) were observed with ISMN, although headache was reported in 19% of the active treatment group (p = 0.0001).

CONCLUSIONS

ISMN added to captopril increased treadmill exercise time in patients with heart failure and a lesser reduction in baseline ejection fraction, although for the group as a whole, the increase in treadmill time was not significant.