2. Academic Validation
  3. Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction

Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction

  • N Engl J Med. 2015 Dec 10;373(24):2314-24. doi: 10.1056/NEJMoa1510774.
Margaret M Redfield 1,  Kevin J Anstrom,  James A Levine,  Gabe A Koepp,  Barry A Borlaug,  Horng H Chen,  Martin M LeWinter,  Susan M Joseph,  Sanjiv J Shah,  Marc J Semigran,  G Michael Felker,  Robert T Cole,  Gordon R Reeves,  Ryan J Tedford,  W H Wilson Tang,  Steven E McNulty,  Eric J Velazquez,  Monica R Shah,  Eugene Braunwald,  NHLBI Heart Failure Clinical Research Network
Affiliations

Affiliation

  • 1 From the Mayo Clinic, Rochester, MN (M.M.R., B.A.B., H.H.C.); Duke Clinical Research Institute (K.J.A., S.E.M., E.J.V.) and Duke University Medical Center (G.M.F.) - both in Durham, NC; Mayo Clinic, Scottsdale, AZ (J.A.L., G.A.K.); University of Vermont Medical Center, Burlington (M.M.L.); Washington University School of Medicine, St. Louis (S.M.J.); Northwestern University, Chicago (S.J.S.); Massachusetts General Hospital (M.J.S.) and Harvard Medical School (E.B.) - both in Boston; Emory University, Atlanta (R.T.C.); Thomas Jefferson University, Philadelphia (G.R.R.); Johns Hopkins University School of Medicine, Baltimore (R.J.T.), and the National Heart, Lung, and Blood Institute, Bethesda (M.R.S.) - both in Maryland; and the Cleveland Clinic Foundation, Cleveland (W.H.W.T.).
PMID: 26549714 DOI: 10.1056/NEJMoa1510774
Abstract

Background: 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.

Methods: 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).

Results: 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.

Conclusions: 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. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT02053493.).

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