Nitrates are commonly prescribed to enhance activity tolerance in patients with heart failure and a preserved ejection fraction. We compared the effect of isosorbide mononitrate or placebo on daily activity in such patients.
In this multicenter, double-blind, crossover study, 110 patients with heart failure and a preserved ejection fraction were randomly assigned to a 6-week dose-escalation regimen of isosorbide mononitrate (from 30 mg to 60 mg to 120 mg once daily) or placebo, with subsequent crossover to the other group for 6 weeks. The primary end point was the daily activity level, quantified as the average daily accelerometer units during the 120-mg phase, as assessed by patient-worn accelerometers. Secondary end points included hours of activity per day during the 120-mg phase, daily accelerometer units during all three dose regimens, quality-of-life scores, 6-minute walk distance, and levels of N-terminal pro–brain natriuretic peptide (NT-proBNP).
In the group receiving the 120-mg dose of isosorbide mononitrate, as compared with the placebo group, there was a nonsignificant trend toward lower daily activity (−381 accelerometer units; 95% confidence interval [CI], −780 to 17; P = 0.06) and a significant decrease in hours of activity per day (−0.30 hours; 95% CI, −0.55 to −0.05; P = 0.02). During all dose regimens, activity in the isosorbide mononitrate group was lower than that in the placebo group (−439 accelerometer units; 95% CI, −792 to −86; P = 0.02). Activity levels decreased progressively and significantly with increased doses of isosorbide mononitrate (but not placebo). There were no significant between-group differences in the 6-minute walk distance, quality-of-life scores, or NT-proBNP levels.
Patients with heart failure and a preserved ejection fraction who received isosorbide mononitrate were less active and did not have better quality of life or submaximal exercise capacity than did patients who received placebo.