Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction

Frederick A. Masoudi, MD, MSPH, FACC, FAHA reviewing Redfield MM et al. N Engl J Med 2015 Nov 8.

The NEAT trial suggests that nitrates adversely affect activity levels in these patients.

In patients with heart failure and preserved left ventricular ejection fraction (HF-pEF), effective approaches to improving outcomes have been elusive. Oral nitrates appear to improve activity tolerance in HF patients with reduced ejection fraction, but their effect in patients with HF-pEF is not known. Researchers conducted this multicenter, blinded, placebo-controlled crossover trial to assess the effect of oral nitrates on exercise tolerance in 110 patients with HF-pEF (mean age 69 years; 57% women) from 20 U.S. sites. All had a left ventricular ejection fraction ≥50%, objective evidence of heart failure, and reported impaired activity due to symptoms of dyspnea, fatigue, or chest pain. Patients were randomized to receive 6 weeks of placebo or isosorbide mononitrate (titrated from 30 mg to 120 mg daily) with crossover to the other treatment for another 6 weeks.

Patients receiving maximal-dose isosorbide had a nonsignificantly lower daily activity level (as measured with an accelerometer) compared with those receiving placebo (381 arbitrary activity units lower than the 9303 units with placebo; P=0.06). Hours of activity per day were significantly lower with isosorbide (-0.3 hours). Those treated with isosorbide at any dose were significantly less physically active (-439 units; P=0.02). Activity progressively decreased with increasing doses of nitrates but not placebo. Blood pressure was lower with treatment, and secondary endpoints, including 6-minute walk distance, health status, and N-terminal pro–brain natriuretic peptide levels, showed no between-group differences.

Citation(s):

Redfield MM et al. Isosorbide mononitrate in heart failure with preserved ejection fraction. N Engl J Med 2015 Nov 8; [e-pub].