"Nitrates in Patients with Heart Failure and Preserved Ejection Fraction (NEAT-HFpEF Trial)".The New England Journal of Medicine. 2015. 373(24):2314-2324.
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Does isosorbide mononitrate improve daily activity in patients with heart failure and a preserved ejection fraction?
Isosorbide mononitrate did not improve the daily activity level, submaximal exercise capacity, quality-of-life scores, or NT-proBNP levels, and actually decreased daily activity levels in patients with heart failure and a preserved ejection fraction.
Heart failure with preserved ejection fraction (HFpEF) often involves exercise intolerance. Nitrates may theoretically alleviate this issue by attenuating pulmonary congestion; however, effectiveness of nitrates in HFpEF is unproven. The NEAT-HFpEF trial showed that isosorbide mononitrate did not improve activity tolerance in HFpEF patients and might actually reduce daily activity.
The findings from NEAT-HFpEF suggest caution when considering isosorbide mononitrate for activity tolerance in HFpEF. No explicit guidelines were provided by the trial.
Multicenter, double-blind, crossover, randomized, placebo-controlled trial.
- **N** = 110 patients with HFpEF - **Interventions**: Isosorbide mononitrate (30 mg to 120 mg once daily) vs placebo - **Setting**: 20 US sites - **Enrollment**: April 7, 2014, to October 30, 2014 - **Mean follow-up**: 6 weeks per treatment phase - **Analysis**: Intention-to-treat - **Primary outcome**: Average daily activity level assessed by accelerometry during 120-mg phase
#### Inclusion Criteria - Heart failure diagnosis - Age ≥50 years - Ejection fraction ≥50% - Objective evidence of heart failure (hospitalization for heart failure, elevated left ventricular end diastolic or pulmonary capillary wedge pressure, elevated NT-proBNP or BNP levels, or echocardiographic evidence of diastolic dysfunction) - Heart failure symptoms as the primary reason for limited activity
#### Exclusion Criteria - Systolic blood pressure <110 mm Hg or >180 mm Hg - Adverse reaction or current use of long-term nitrate or phosphodiesterase type 5 inhibitor therapy
#### Baseline Characteristics - Mean age 69 years, 57% female - Majority were white and obese - Majority had controlled blood pressure and multiple coexisting illnesses - Most patients were on multiple cardiovascular medications - Mean ejection fraction was 63% ### Interventions - Isosorbide mononitrate - dose-escalation regimen 30 mg to 120 mg once daily for 6 weeks. - Placebo for 6 weeks. - Crossover design, so patients received both treatments sequentially with washout period.
#### Primary Outcome - No significant improvement in average daily activity levels during the 120-mg phase of isosorbide mononitrate vs placebo.
- Decrease in hours of activity per day with isosorbide mononitrate. - No significant difference in 6-minute walk distance, quality-of-life scores, or NT-proBNP levels compared to placebo. ### Criticisms - Rapid dose escalation of isosorbide mononitrate may have limited assessment of tolerability. - Absence of longer-term outcomes assessment. - No improvement in exercise tolerance and reduction of daily activity levels limits applicability.
National Heart, Lung, and Blood Institute (NHLBI) grants.
Full article and supplementary materials available at NEJM.org.