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 Solomon; Nancy K Sweitzer; Song Yang; Sonja M McKinlay; TOPCAT Investigators

doi:10.1056/NEJMoa1313731

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, TOPCAT Investigators

Research output: Contribution to journal › Article › peer-review

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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. (Funded by the National Heart, Lung, and Blood Institute; TOPCAT ClinicalTrials.gov number, NCT00094302.).

Original language	English (US)
Pages (from-to)	1383-92
Number of pages	10
Journal	The New England journal of medicine
Volume	370
Issue number	15
DOIs	https://doi.org/10.1056/NEJMoa1313731
State	Published - Apr 10 2014
Externally published	Yes

Keywords

Aged
Aged, 80 and over
Cardiovascular Diseases
Double-Blind Method
Female
Follow-Up Studies
Heart Failure
Hospitalization
Humans
Incidence
Kaplan-Meier Estimate
Male
Middle Aged
Mineralocorticoid Receptor Antagonists
Spironolactone
Stroke Volume
Treatment Failure

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10.1056/NEJMoa1313731

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Pitt, B., Pfeffer, M. A., Assmann, S. F., Boineau, R., Anand, I. S., Claggett, B., Clausell, N., Desai, A. S., Diaz, R., Fleg, J. L., Gordeev, I., Harty, B., Heitner, J. F., Kenwood, C. T., Lewis, E. F., O'Meara, E., Probstfield, J. L., Shaburishvili, T., Shah, S. J., ... TOPCAT Investigators (2014). Spironolactone for heart failure with preserved ejection fraction. The New England journal of medicine, 370(15), 1383-92. https://doi.org/10.1056/NEJMoa1313731

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 & TOPCAT Investigators 2014, 'Spironolactone for heart failure with preserved ejection fraction', The New England journal of medicine, vol. 370, no. 15, pp. 1383-92. https://doi.org/10.1056/NEJMoa1313731

@article{45648301e2b440149f3988f52f5c08bc,

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. (Funded by the National Heart, Lung, and Blood Institute; TOPCAT ClinicalTrials.gov number, NCT00094302.).",

keywords = "Aged, Aged, 80 and over, Cardiovascular Diseases, Double-Blind Method, Female, Follow-Up Studies, Heart Failure, Hospitalization, Humans, Incidence, Kaplan-Meier Estimate, Male, Middle Aged, Mineralocorticoid Receptor Antagonists, Spironolactone, Stroke Volume, Treatment 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} and {TOPCAT Investigators}",

year = "2014",

month = apr,

day = "10",

doi = "10.1056/NEJMoa1313731",

language = "English (US)",

volume = "370",

pages = "1383--92",

journal = "The New England journal of medicine",

issn = "0028-4793",

publisher = "Massachussetts Medical Society",

number = "15",

}

TY - JOUR

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

AU - TOPCAT Investigators

PY - 2014/4/10

Y1 - 2014/4/10

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. (Funded by the National Heart, Lung, and Blood Institute; TOPCAT ClinicalTrials.gov number, NCT00094302.).

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. (Funded by the National Heart, Lung, and Blood Institute; TOPCAT ClinicalTrials.gov number, NCT00094302.).

KW - Aged

KW - Aged, 80 and over

KW - Cardiovascular Diseases

KW - Double-Blind Method

KW - Female

KW - Follow-Up Studies

KW - Heart Failure

KW - Hospitalization

KW - Humans

KW - Incidence

KW - Kaplan-Meier Estimate

KW - Male

KW - Middle Aged

KW - Mineralocorticoid Receptor Antagonists

KW - Spironolactone

KW - Stroke Volume

KW - Treatment Failure

U2 - 10.1056/NEJMoa1313731

DO - 10.1056/NEJMoa1313731

M3 - Article

C2 - 24716680

SN - 0028-4793

VL - 370

SP - 1383

EP - 1392

JO - The New England journal of medicine

JF - The New England journal of medicine

IS - 15

ER -

Spironolactone for heart failure with preserved ejection fraction

Abstract

Keywords

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