Efficacy and safety of spironolactone in acute heart failure: The ATHENA-HF randomized clinical trial

National Heart Lung and Blood Institute Heart Failure Clinical Research Network

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

IMPORTANCE: Persistent congestion is associated with worse outcomes in acute heart failure (AHF). Mineralocorticoid receptor antagonists administered at high doses may relieve congestion, overcome diuretic resistance, and mitigate the effects of adverse neurohormonal activation in AHF. OBJECTIVE: To assess the effect of high-dose spironolactone and usual care on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels compared with usual care alone. DESIGN, SETTING, AND PARTICIPANTS: This double-blind and placebo (or low-dose)-controlled randomized clinical trial was conducted in 22 US acute care hospitals among patients with AHF who were previously receiving no or low-dose (12.5 mg or 25 mg daily) spironolactone and had NT-proBNP levels of 1000 pg/mL or more or B-type natriuretic peptide levels of 250 pg/mL or more, regardless of ejection fraction. INTERVENTIONS: High-dose spironolactone (100 mg) vs placebo or 25 mg spironolactone (usual care) daily for 96 hours MAIN OUTCOMES AND MEASURES: The primary end point was the change in NT-proBNP levels from baseline to 96 hours. Secondary end points included the clinical congestion score, dyspnea assessment, net urine output, and net weight change. Safety end points included hyperkalemia and changes in renal function. RESULTS: A total of 360 patients were randomized, of whom the median age was 65 years, 129 (36%) were women, 200 (55.5%) were white, 151 (42%) were black, 8 (2%) were Hispanic or Latino, 9 (2.5%) were of other race/ethnicity, and the median left ventricular ejection fraction was 34%. Baseline median (interquartile range) NT-proBNP levels were 4601 (2697-9596) pg/mL among the group treated with high-dose spironolactone and 3753 (1968-7633) pg/mL among the group who received usual care. There was no significant difference in the log NT-proBNP reduction between the 2 groups (−0.55 [95% CI, −0.92 to −0.18] with high-dose spironolactone and −0.49 [95% CI, −0.98 to −0.14] with usual care, P = .57). None of the secondary end point or day-30 all-cause mortality or heart failure hospitalization rate differed between the 2 groups. The changes in serum potassium and estimated glomerular filtration rate at 24, 48, 72, and 96 hours. were similar between the 2 groups. CONCLUSIONS AND RELEVANCE: Adding treatment with high-dose spironolactone to usual care for patients with AHF for 96 hours was well tolerated but did not improve the primary or secondary efficacy end points. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02235077.

Original languageEnglish (US)
Pages (from-to)950-958
Number of pages9
JournalJAMA Cardiology
Volume2
Issue number9
DOIs
StatePublished - Sep 1 2017

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Spironolactone
Brain Natriuretic Peptide
Randomized Controlled Trials
Heart Failure
Safety
Hispanic Americans
Placebos
Mineralocorticoid Receptor Antagonists
Hyperkalemia
Glomerular Filtration Rate
Diuretics
Stroke Volume
Dyspnea
Patient Care
Potassium
Hospitalization
Urine
Kidney
Weights and Measures
Mortality

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

National Heart Lung and Blood Institute Heart Failure Clinical Research Network (2017). Efficacy and safety of spironolactone in acute heart failure: The ATHENA-HF randomized clinical trial. JAMA Cardiology, 2(9), 950-958. https://doi.org/10.1001/jamacardio.2017.2198

Efficacy and safety of spironolactone in acute heart failure : The ATHENA-HF randomized clinical trial. / National Heart Lung and Blood Institute Heart Failure Clinical Research Network.

In: JAMA Cardiology, Vol. 2, No. 9, 01.09.2017, p. 950-958.

Research output: Contribution to journalArticle

National Heart Lung and Blood Institute Heart Failure Clinical Research Network 2017, 'Efficacy and safety of spironolactone in acute heart failure: The ATHENA-HF randomized clinical trial', JAMA Cardiology, vol. 2, no. 9, pp. 950-958. https://doi.org/10.1001/jamacardio.2017.2198
National Heart Lung and Blood Institute Heart Failure Clinical Research Network. Efficacy and safety of spironolactone in acute heart failure: The ATHENA-HF randomized clinical trial. JAMA Cardiology. 2017 Sep 1;2(9):950-958. https://doi.org/10.1001/jamacardio.2017.2198
National Heart Lung and Blood Institute Heart Failure Clinical Research Network. / Efficacy and safety of spironolactone in acute heart failure : The ATHENA-HF randomized clinical trial. In: JAMA Cardiology. 2017 ; Vol. 2, No. 9. pp. 950-958.
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abstract = "IMPORTANCE: Persistent congestion is associated with worse outcomes in acute heart failure (AHF). Mineralocorticoid receptor antagonists administered at high doses may relieve congestion, overcome diuretic resistance, and mitigate the effects of adverse neurohormonal activation in AHF. OBJECTIVE: To assess the effect of high-dose spironolactone and usual care on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels compared with usual care alone. DESIGN, SETTING, AND PARTICIPANTS: This double-blind and placebo (or low-dose)-controlled randomized clinical trial was conducted in 22 US acute care hospitals among patients with AHF who were previously receiving no or low-dose (12.5 mg or 25 mg daily) spironolactone and had NT-proBNP levels of 1000 pg/mL or more or B-type natriuretic peptide levels of 250 pg/mL or more, regardless of ejection fraction. INTERVENTIONS: High-dose spironolactone (100 mg) vs placebo or 25 mg spironolactone (usual care) daily for 96 hours MAIN OUTCOMES AND MEASURES: The primary end point was the change in NT-proBNP levels from baseline to 96 hours. Secondary end points included the clinical congestion score, dyspnea assessment, net urine output, and net weight change. Safety end points included hyperkalemia and changes in renal function. RESULTS: A total of 360 patients were randomized, of whom the median age was 65 years, 129 (36{\%}) were women, 200 (55.5{\%}) were white, 151 (42{\%}) were black, 8 (2{\%}) were Hispanic or Latino, 9 (2.5{\%}) were of other race/ethnicity, and the median left ventricular ejection fraction was 34{\%}. Baseline median (interquartile range) NT-proBNP levels were 4601 (2697-9596) pg/mL among the group treated with high-dose spironolactone and 3753 (1968-7633) pg/mL among the group who received usual care. There was no significant difference in the log NT-proBNP reduction between the 2 groups (−0.55 [95{\%} CI, −0.92 to −0.18] with high-dose spironolactone and −0.49 [95{\%} CI, −0.98 to −0.14] with usual care, P = .57). None of the secondary end point or day-30 all-cause mortality or heart failure hospitalization rate differed between the 2 groups. The changes in serum potassium and estimated glomerular filtration rate at 24, 48, 72, and 96 hours. were similar between the 2 groups. CONCLUSIONS AND RELEVANCE: Adding treatment with high-dose spironolactone to usual care for patients with AHF for 96 hours was well tolerated but did not improve the primary or secondary efficacy end points. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02235077.",
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T1 - Efficacy and safety of spironolactone in acute heart failure

T2 - The ATHENA-HF randomized clinical trial

AU - National Heart Lung and Blood Institute Heart Failure Clinical Research Network

AU - Butler, Javed

AU - Anstrom, Kevin J.

AU - Felker, G. Michael

AU - Givertz, Michael M.

AU - Kalogeropoulos, Andreas P.

AU - Konstam, Marvin A.

AU - Mann, Douglas L.

AU - Margulies, Kenneth B.

AU - McNulty, Steven E.

AU - Mentz, Robert J.

AU - Redfield, Margaret May

AU - Tang, W. H.Wilson

AU - Whellan, David J.

AU - Shah, Monica

AU - Desvigne-Nickens, Patrice

AU - Hernandez, Adrian F.

AU - Braunwald, Eugene

PY - 2017/9/1

Y1 - 2017/9/1

N2 - IMPORTANCE: Persistent congestion is associated with worse outcomes in acute heart failure (AHF). Mineralocorticoid receptor antagonists administered at high doses may relieve congestion, overcome diuretic resistance, and mitigate the effects of adverse neurohormonal activation in AHF. OBJECTIVE: To assess the effect of high-dose spironolactone and usual care on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels compared with usual care alone. DESIGN, SETTING, AND PARTICIPANTS: This double-blind and placebo (or low-dose)-controlled randomized clinical trial was conducted in 22 US acute care hospitals among patients with AHF who were previously receiving no or low-dose (12.5 mg or 25 mg daily) spironolactone and had NT-proBNP levels of 1000 pg/mL or more or B-type natriuretic peptide levels of 250 pg/mL or more, regardless of ejection fraction. INTERVENTIONS: High-dose spironolactone (100 mg) vs placebo or 25 mg spironolactone (usual care) daily for 96 hours MAIN OUTCOMES AND MEASURES: The primary end point was the change in NT-proBNP levels from baseline to 96 hours. Secondary end points included the clinical congestion score, dyspnea assessment, net urine output, and net weight change. Safety end points included hyperkalemia and changes in renal function. RESULTS: A total of 360 patients were randomized, of whom the median age was 65 years, 129 (36%) were women, 200 (55.5%) were white, 151 (42%) were black, 8 (2%) were Hispanic or Latino, 9 (2.5%) were of other race/ethnicity, and the median left ventricular ejection fraction was 34%. Baseline median (interquartile range) NT-proBNP levels were 4601 (2697-9596) pg/mL among the group treated with high-dose spironolactone and 3753 (1968-7633) pg/mL among the group who received usual care. There was no significant difference in the log NT-proBNP reduction between the 2 groups (−0.55 [95% CI, −0.92 to −0.18] with high-dose spironolactone and −0.49 [95% CI, −0.98 to −0.14] with usual care, P = .57). None of the secondary end point or day-30 all-cause mortality or heart failure hospitalization rate differed between the 2 groups. The changes in serum potassium and estimated glomerular filtration rate at 24, 48, 72, and 96 hours. were similar between the 2 groups. CONCLUSIONS AND RELEVANCE: Adding treatment with high-dose spironolactone to usual care for patients with AHF for 96 hours was well tolerated but did not improve the primary or secondary efficacy end points. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02235077.

AB - IMPORTANCE: Persistent congestion is associated with worse outcomes in acute heart failure (AHF). Mineralocorticoid receptor antagonists administered at high doses may relieve congestion, overcome diuretic resistance, and mitigate the effects of adverse neurohormonal activation in AHF. OBJECTIVE: To assess the effect of high-dose spironolactone and usual care on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels compared with usual care alone. DESIGN, SETTING, AND PARTICIPANTS: This double-blind and placebo (or low-dose)-controlled randomized clinical trial was conducted in 22 US acute care hospitals among patients with AHF who were previously receiving no or low-dose (12.5 mg or 25 mg daily) spironolactone and had NT-proBNP levels of 1000 pg/mL or more or B-type natriuretic peptide levels of 250 pg/mL or more, regardless of ejection fraction. INTERVENTIONS: High-dose spironolactone (100 mg) vs placebo or 25 mg spironolactone (usual care) daily for 96 hours MAIN OUTCOMES AND MEASURES: The primary end point was the change in NT-proBNP levels from baseline to 96 hours. Secondary end points included the clinical congestion score, dyspnea assessment, net urine output, and net weight change. Safety end points included hyperkalemia and changes in renal function. RESULTS: A total of 360 patients were randomized, of whom the median age was 65 years, 129 (36%) were women, 200 (55.5%) were white, 151 (42%) were black, 8 (2%) were Hispanic or Latino, 9 (2.5%) were of other race/ethnicity, and the median left ventricular ejection fraction was 34%. Baseline median (interquartile range) NT-proBNP levels were 4601 (2697-9596) pg/mL among the group treated with high-dose spironolactone and 3753 (1968-7633) pg/mL among the group who received usual care. There was no significant difference in the log NT-proBNP reduction between the 2 groups (−0.55 [95% CI, −0.92 to −0.18] with high-dose spironolactone and −0.49 [95% CI, −0.98 to −0.14] with usual care, P = .57). None of the secondary end point or day-30 all-cause mortality or heart failure hospitalization rate differed between the 2 groups. The changes in serum potassium and estimated glomerular filtration rate at 24, 48, 72, and 96 hours. were similar between the 2 groups. CONCLUSIONS AND RELEVANCE: Adding treatment with high-dose spironolactone to usual care for patients with AHF for 96 hours was well tolerated but did not improve the primary or secondary efficacy end points. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02235077.

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