Spironolactone for heart failure with preserved ejection fraction

Bertram Pitt, Marc A. Pfeffer, Susan F. Assmann, Robin Boineau, Inder S. Anand, Brian Claggett, Nadine Clausell, Akshay S. Desai, Rafael Diaz, Jerome L. Fleg, Ivan Gordeev, Brian Harty, John F. Heitner, Christopher T. Kenwood, Eldrin F. Lewis, Eileen O'Meara, Jeffrey L. Probstfield, Tamaz Shaburishvili, Sanjiv J. Shah, Scott D. SolomonNancy K Sweitzer, Song Yang, Sonja M. McKinlay

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction. METHODS: In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive either spironolactone (15 to 45 mg daily) or placebo. The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. RESULTS: With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6%) and 351 of 1723 patients in the placebo group (20.4%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.77 to 1.04; P = 0.14). Of the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard ratio, 0.83; 95% CI, 0.69 to 0.99, P = 0.04). Neither total deaths nor hospitalizations for any reason were significantly reduced by spironolactone. Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of the rate of hyperkalemia (18.7%, vs. 9.1% in the placebo group) but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events, a serum creatinine level of 3.0 mg per deciliter (265 μmol per liter) or higher, or dialysis. CONCLUSIONS: In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure.

Original languageEnglish (US)
Pages (from-to)1383-1392
Number of pages10
JournalNew England Journal of Medicine
Volume370
Issue number15
DOIs
StatePublished - 2014
Externally publishedYes

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Spironolactone
Heart Failure
Hospitalization
Placebos
Stroke Volume
Heart Arrest
Cause of Death
Creatinine
Incidence
Confidence Intervals
Mineralocorticoid Receptor Antagonists
Hyperkalemia
Hypokalemia
Serum
Dialysis
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

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Pitt, B., Pfeffer, M. A., Assmann, S. F., Boineau, R., Anand, I. S., Claggett, B., ... McKinlay, S. M. (2014). Spironolactone for heart failure with preserved ejection fraction. New England Journal of Medicine, 370(15), 1383-1392. https://doi.org/10.1056/NEJMoa1313731

Spironolactone for heart failure with preserved ejection fraction. / Pitt, Bertram; Pfeffer, Marc A.; Assmann, Susan F.; Boineau, Robin; Anand, Inder S.; Claggett, Brian; Clausell, Nadine; Desai, Akshay S.; Diaz, Rafael; Fleg, Jerome L.; Gordeev, Ivan; Harty, Brian; Heitner, John F.; Kenwood, Christopher T.; Lewis, Eldrin F.; O'Meara, Eileen; Probstfield, Jeffrey L.; Shaburishvili, Tamaz; Shah, Sanjiv J.; Solomon, Scott D.; Sweitzer, Nancy K; Yang, Song; McKinlay, Sonja M.

In: New England Journal of Medicine, Vol. 370, No. 15, 2014, p. 1383-1392.

Research output: Contribution to journalArticle

Pitt, B, Pfeffer, MA, Assmann, SF, Boineau, R, Anand, IS, Claggett, B, Clausell, N, Desai, AS, Diaz, R, Fleg, JL, Gordeev, I, Harty, B, Heitner, JF, Kenwood, CT, Lewis, EF, O'Meara, E, Probstfield, JL, Shaburishvili, T, Shah, SJ, Solomon, SD, Sweitzer, NK, Yang, S & McKinlay, SM 2014, 'Spironolactone for heart failure with preserved ejection fraction', New England Journal of Medicine, vol. 370, no. 15, pp. 1383-1392. https://doi.org/10.1056/NEJMoa1313731
Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B et al. Spironolactone for heart failure with preserved ejection fraction. New England Journal of Medicine. 2014;370(15):1383-1392. https://doi.org/10.1056/NEJMoa1313731
Pitt, Bertram ; Pfeffer, Marc A. ; Assmann, Susan F. ; Boineau, Robin ; Anand, Inder S. ; Claggett, Brian ; Clausell, Nadine ; Desai, Akshay S. ; Diaz, Rafael ; Fleg, Jerome L. ; Gordeev, Ivan ; Harty, Brian ; Heitner, John F. ; Kenwood, Christopher T. ; Lewis, Eldrin F. ; O'Meara, Eileen ; Probstfield, Jeffrey L. ; Shaburishvili, Tamaz ; Shah, Sanjiv J. ; Solomon, Scott D. ; Sweitzer, Nancy K ; Yang, Song ; McKinlay, Sonja M. / Spironolactone for heart failure with preserved ejection fraction. In: New England Journal of Medicine. 2014 ; Vol. 370, No. 15. pp. 1383-1392.
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title = "Spironolactone for heart failure with preserved ejection fraction",
abstract = "BACKGROUND: Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction. METHODS: In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45{\%} or more to receive either spironolactone (15 to 45 mg daily) or placebo. The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. RESULTS: With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6{\%}) and 351 of 1723 patients in the placebo group (20.4{\%}) (hazard ratio, 0.89; 95{\%} confidence interval [CI], 0.77 to 1.04; P = 0.14). Of the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0{\%}] vs. 245 patients [14.2{\%}]; hazard ratio, 0.83; 95{\%} CI, 0.69 to 0.99, P = 0.04). Neither total deaths nor hospitalizations for any reason were significantly reduced by spironolactone. Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of the rate of hyperkalemia (18.7{\%}, vs. 9.1{\%} in the placebo group) but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events, a serum creatinine level of 3.0 mg per deciliter (265 μmol per liter) or higher, or dialysis. CONCLUSIONS: In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure.",
author = "Bertram Pitt and Pfeffer, {Marc A.} and Assmann, {Susan F.} and Robin Boineau and Anand, {Inder S.} and Brian Claggett and Nadine Clausell and Desai, {Akshay S.} and Rafael Diaz and Fleg, {Jerome L.} and Ivan Gordeev and Brian Harty and Heitner, {John F.} and Kenwood, {Christopher T.} and Lewis, {Eldrin F.} and Eileen O'Meara and Probstfield, {Jeffrey L.} and Tamaz Shaburishvili and Shah, {Sanjiv J.} and Solomon, {Scott D.} and Sweitzer, {Nancy K} and Song Yang and McKinlay, {Sonja M.}",
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T1 - Spironolactone for heart failure with preserved ejection fraction

AU - Pitt, Bertram

AU - Pfeffer, Marc A.

AU - Assmann, Susan F.

AU - Boineau, Robin

AU - Anand, Inder S.

AU - Claggett, Brian

AU - Clausell, Nadine

AU - Desai, Akshay S.

AU - Diaz, Rafael

AU - Fleg, Jerome L.

AU - Gordeev, Ivan

AU - Harty, Brian

AU - Heitner, John F.

AU - Kenwood, Christopher T.

AU - Lewis, Eldrin F.

AU - O'Meara, Eileen

AU - Probstfield, Jeffrey L.

AU - Shaburishvili, Tamaz

AU - Shah, Sanjiv J.

AU - Solomon, Scott D.

AU - Sweitzer, Nancy K

AU - Yang, Song

AU - McKinlay, Sonja M.

PY - 2014

Y1 - 2014

N2 - BACKGROUND: Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction. METHODS: In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive either spironolactone (15 to 45 mg daily) or placebo. The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. RESULTS: With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6%) and 351 of 1723 patients in the placebo group (20.4%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.77 to 1.04; P = 0.14). Of the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard ratio, 0.83; 95% CI, 0.69 to 0.99, P = 0.04). Neither total deaths nor hospitalizations for any reason were significantly reduced by spironolactone. Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of the rate of hyperkalemia (18.7%, vs. 9.1% in the placebo group) but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events, a serum creatinine level of 3.0 mg per deciliter (265 μmol per liter) or higher, or dialysis. CONCLUSIONS: In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure.

AB - BACKGROUND: Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction. METHODS: In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive either spironolactone (15 to 45 mg daily) or placebo. The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. RESULTS: With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6%) and 351 of 1723 patients in the placebo group (20.4%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.77 to 1.04; P = 0.14). Of the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard ratio, 0.83; 95% CI, 0.69 to 0.99, P = 0.04). Neither total deaths nor hospitalizations for any reason were significantly reduced by spironolactone. Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of the rate of hyperkalemia (18.7%, vs. 9.1% in the placebo group) but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events, a serum creatinine level of 3.0 mg per deciliter (265 μmol per liter) or higher, or dialysis. CONCLUSIONS: In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure.

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