Nitrate’s Effect on Activity Tolerance in Heart Failure With Preserved Ejection Fraction - NEAT-HFpEF

Description:

The goal of the trial was to evaluate treatment with a long-acting nitrate compared with placebo among patients with heart failure with preserved ejection fraction (HFpEF).

Contribution to the Literature: The NEAT-HFpEF trial failed to show that long-acting nitrates in HFpEF improved exercise tolerance.

Study Design

  • Randomized
  • Parallel
  • Double-blind
  • Placebo
  • Crossover

Patients with HFpEF were randomized to a long-acting nitrate (n = 51) versus placebo (n = 59). Study medication (isosorbide mononitrate or placebo) was up-titrated to 120 mg over a 6-week period. After a 2-week washout period, subjects crossed over to the opposite treatment assignment with up-titration for 6 weeks.

  • Total number of enrollees: 110
  • Duration of follow-up: 12 weeks
  • Mean patient age: 69 years
  • Percentage female: 57%
  • Percentage diabetics: 36%

Inclusion criteria:

  • Patients ≥50 years of age with New York Heart Association (NYHA) class II-IV symptoms and left ventricular EF (LVEF) ≥50%
  • HF symptoms are the primary factor for exercise intolerance

At least one of the following:

  • HF hospitalization
  • Elevated B-type natriuretic peptide (BNP) or NT-proBNP
  • Elevated rest of exercise pulmonary artery wedge pressure on right heart catheterization
  • Diastolic dysfunction on echocardiography

Other salient features/characteristics:

  • Chronic kidney disease: 54%
  • Mean systolic blood pressure: 132 mm Hg
  • Mean LVEF: 63%

Exclusion criteria:

  • Systolic blood pressure <110 mm Hg
  • Adverse reaction or current use of a long-acting nitrate
  • Phosphodiesterase type-5 inhibitor therapy

Principal Findings:

The primary outcome, average daily accelerometer units (ADAU), was nonsignificantly less for the 120 mg long-acting nitrate dose compared with placebo (-381 ADAU, p = 0.06).

Secondary outcomes:

  • Hours active/day: -0.3 hours for long-acting nitrate vs. placebo (p = 0.02)
  • Six-minute walk: 0.57 m for long-acting nitrate vs. placebo (p = 0.91)
  • Discontinuation of study medication: 16 patients in the long-acting nitrate group vs. 9 patients in the placebo group

Interpretation:

Among individuals with HF due to pEF, long-acting nitrates failed to improve exercise tolerance compared with placebo. More patients in the long-acting nitrate group discontinued study medication due to side effects. Optimal treatment of HF due to pEF remains challenging and poorly defined.

References:

Redfield MM, Anstrom KJ, Levine JA, et al. Isosorbide mononitrate in heart failure with preserved ejection fraction. N Engl J Med 2015;Nov 8:[Epub ahead of print].

Presented by Dr. Margaret M. Redfield at the American Heart Association Scientific Sessions, Orlando, FL, November 8, 2015.

Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Exercise

Keywords: Exercise Tolerance, Heart Failure, Isosorbide Dinitrate, Nitrates, Nitrogen Oxides, Stroke Volume, Walking, AHA Annual Scientific Sessions


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