Isosorbide mononitrate in heart failure with preserved ejection fraction

Margaret May Redfield, Kevin J. Anstrom, James A. Levine, Gabe A. Koepp, Barry A Borlaug, Horng Haur 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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)2314-2324
Number of pages11
JournalNew England Journal of Medicine
Volume373
Issue number24
DOIs
StatePublished - Dec 10 2015

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isosorbide-5-mononitrate
Heart Failure
Placebos
Brain Natriuretic Peptide
Quality of Life
Confidence Intervals
Double-Blind Method
Nitrates
Cross-Over Studies
Exercise

ASJC Scopus subject areas

  • Medicine(all)

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Isosorbide mononitrate in heart failure with preserved ejection fraction. / Redfield, Margaret May; Anstrom, Kevin J.; Levine, James A.; Koepp, Gabe A.; Borlaug, Barry A; Chen, Horng Haur; LeWinter, Martin M.; Joseph, Susan M.; Shah, Sanjiv J.; Semigran, Marc J.; Felker, G. Michael; Cole, Robert T.; Reeves, Gordon R.; Tedford, Ryan J.; Tang, W. H Wilson; McNulty, Steven E.; Velazquez, Eric J.; Shah, Monica R.; Braunwald, Eugene.

In: New England Journal of Medicine, Vol. 373, No. 24, 10.12.2015, p. 2314-2324.

Research output: Contribution to journalArticle

Redfield, MM, Anstrom, KJ, Levine, JA, Koepp, GA, Borlaug, BA, Chen, HH, LeWinter, MM, Joseph, SM, Shah, SJ, Semigran, MJ, Felker, GM, Cole, RT, Reeves, GR, Tedford, RJ, Tang, WHW, McNulty, SE, Velazquez, EJ, Shah, MR & Braunwald, E 2015, 'Isosorbide mononitrate in heart failure with preserved ejection fraction', New England Journal of Medicine, vol. 373, no. 24, pp. 2314-2324. https://doi.org/10.1056/NEJMoa1510774
Redfield, Margaret May ; Anstrom, Kevin J. ; Levine, James A. ; Koepp, Gabe A. ; Borlaug, Barry A ; Chen, Horng Haur ; LeWinter, Martin M. ; Joseph, Susan M. ; Shah, Sanjiv J. ; Semigran, Marc J. ; Felker, G. Michael ; Cole, Robert T. ; Reeves, Gordon R. ; Tedford, Ryan J. ; Tang, W. H Wilson ; McNulty, Steven E. ; Velazquez, Eric J. ; Shah, Monica R. ; Braunwald, Eugene. / Isosorbide mononitrate in heart failure with preserved ejection fraction. In: New England Journal of Medicine. 2015 ; Vol. 373, No. 24. pp. 2314-2324.
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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.",
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T1 - Isosorbide mononitrate in heart failure with preserved ejection fraction

AU - Redfield, Margaret May

AU - Anstrom, Kevin J.

AU - Levine, James A.

AU - Koepp, Gabe A.

AU - Borlaug, Barry A

AU - Chen, Horng Haur

AU - LeWinter, Martin M.

AU - Joseph, Susan M.

AU - Shah, Sanjiv J.

AU - Semigran, Marc J.

AU - Felker, G. Michael

AU - Cole, Robert T.

AU - Reeves, Gordon R.

AU - Tedford, Ryan J.

AU - Tang, W. H Wilson

AU - McNulty, Steven E.

AU - Velazquez, Eric J.

AU - Shah, Monica R.

AU - Braunwald, Eugene

PY - 2015/12/10

Y1 - 2015/12/10

N2 - 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.

AB - 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.

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