Clinical Question

Should nitrates be prescribed for patients who have heart failure with preserved ejection fraction?

Bottom Line

Patients who have heart failure with preserved ejection fraction had decreased levels of activity and more adverse events when they were receiving isosorbide mononitrate than when they were taking a placebo. Moreover, activity levels decreased with increases in the dose of the drug, suggesting a strong correlation. However, almost 90% of the patients in this study were white, which may limit its generalizability. (Level of Evidence = 1b)

Synopsis

Previous studies note that up to 50% of patients who have heart failure with preserved ejection fraction receive nitrates, but the effectiveness of this therapy has not been extensively studied in this population. In the current trial, investigators enrolled patients with a diagnosis of heart failure with preserved ejection fraction who had limited activity levels because of the symptoms of heart failure (dyspnea, chest pain, or fatigue). The patients (N = 110) were randomized to receive 30 mg of isosorbide mononitrate tablets or matching placebo tablets for six weeks, followed by the other therapy (crossover) for another six weeks. For each six-week period, patients took no study drug for the first two weeks, one tablet for the third week, two tablets for the fourth week, and four tablets for the remaining weeks.

All patients wore accelerometers to measure their movement. One accelerometer unit indicates a cumulative 15 minutes of activity. The patients in the study had a mean age of 69 years and a New York Heart Association functional class of II or III; 90% were white. Analysis was by intention to treat. When comparing the group receiving 120 mg of isosorbide mononitrate with the matching placebo group, there was a trend toward decreased daily activity in the treatment group (−381 accelerometer units; 95% confidence interval, −780 to 17; P = .06), as well as a statistically significant decrease in hours of daily activity (−0.30 hours; 95% confidence interval, −0.55 to −0.05; P = .02). Furthermore, there was a dose-dependent decrease in daily activity in the patients receiving the active drug. No significant differences were detected in exercise capacity (as measured by the six-minute walk test) or quality-of-life scores, but more patients experienced adverse events (including worsening heart failure and syncope) during the isosorbide mononitrate phase of the trial than during the placebo phase.

Study design: Crossover trial (randomized)

Funding source: Government

Allocation: Concealed

Setting: Outpatient (primary care)

Reference: RedfieldMMAnstromKJLevineJAet alNHLBI Heart Failure Clinical Research NetworkIsosorbide mononitrate in heart failure with preserved ejection fraction. N Engl J Med2015; 373( 24): 2314– 2324.