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Spironolactone in Acute Heart Failure Patients With Renal Dysfunction and Risk Factors for Diuretic Resistance: From the ATHENA-HF Trial.

ABSTRACT: BACKGROUND:Acute heart failure (HF) patients with renal insufficiency and risk factors for diuretic resistance may be most likely to derive incremental improvement in congestion with the addition of spironolactone. METHODS:The Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure (ATHENA-HF) trial randomized 360 acute HF patients with reduced or preserved ejection fraction to spironolactone 100 mg daily or usual care for 96 hours. The current analysis assessed the effects of study therapy within tertiles of baseline estimated glomerular filtration rate (eGFR) and subgroups at heightened risk for diuretic resistance. RESULTS:Across eGFR tertiles, there was no incremental benefit of high-dose spironolactone on any efficacy endpoint, including changes in log N-terminal pro-B-type natriuretic peptide and signs and symptoms of congestion (all P for interaction ? 0.06). High-dose spironolactone had no significant effect on N-terminal pro-B-type natriuretic peptide reduction regardless of blood pressure, diabetes mellitus status, and loop diuretic dose (all P for interaction ? 0.38). In-hospital changes in serum potassium and creatinine were similar between treatment groups for all GFR tertiles (all P for interaction ? 0.18). Rates of inpatient worsening HF, 30-day worsening HF, and 60-day all-cause mortality were numerically higher among patients with lower baseline eGFR, but relative effects of study treatment did not differ with renal function (all P for interaction ? 0.27). CONCLUSIONS:High-dose spironolactone did not improve congestion over usual care among patients with acute HF, irrespective of renal function and risk factors for diuretic resistance. In-hospital initiation or continuation of spironolactone was safe during the inpatient stay, even when administered at high doses to patients with moderate renal dysfunction.

SUBMITTER: Greene SJ

PROVIDER: S-EPMC6685766 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Spironolactone in Acute Heart Failure Patients With Renal Dysfunction and Risk Factors for Diuretic Resistance: From the ATHENA-HF Trial.

Greene Stephen J SJ Felker G Michael GM Giczewska Anna A Kalogeropoulos Andreas P AP Ambrosy Andrew P AP Chakraborty Hrishikesh H DeVore Adam D AD Fudim Marat M McNulty Steven E SE Mentz Robert J RJ Vaduganathan Muthiah M Hernandez Adrian F AF Butler Javed J

The Canadian journal of cardiology 20190207 9

<h4>Background</h4>Acute heart failure (HF) patients with renal insufficiency and risk factors for diuretic resistance may be most likely to derive incremental improvement in congestion with the addition of spironolactone.<h4>Methods</h4>The Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure (ATHENA-HF) trial randomized 360 acute HF patients with reduced or preserved ejection fraction to spironolactone 100 mg daily or usual care for 96 hours. The current analys ...[more]

PMID: 31230825

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Project description:ImportancePersistent 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.ObjectiveTo 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 participantsThis 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.InterventionsHigh-dose spironolactone (100 mg) vs placebo or 25 mg spironolactone (usual care) daily for 96 hours.Main outcomes and measuresThe 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.ResultsA 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 relevanceAdding 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 registrationclinicaltrials.gov Identifier: NCT02235077.

Project description:BackgroundLoop diuretics are common therapy for emergency department (ED) patients with acute heart failure (AHF). Diuretic resistance (DR) is a term used to describe blunted natriuretic response to loop diuretics. It would be important to detect DR prior to it becoming clinically apparent, so early interventions can be initiated. However, several definitions have been proposed, and it is not clear if they identify similar patients. We compared these definitions and described the clinical characteristics of patients who fulfilled them.MethodsTo qualify for this secondary analysis of 1033 ED patients with AHF, all patients needed to receive intravenous diuretics in the ED and have urine available within 24 h of their ED evaluation. A poor diuretic response, suggesting DR, was characterized by (1) a fractional sodium excretion (FeNa) of less than 0.2%; (2) spot urinary sodium of less than 50 meq/L; and (3) a urinary Na/K ratio <1.0. McNemar's test was used to compare the different cohorts identified by the three definitions. Secondary analyses evaluated associations between each DR definition and hospital length of stay (LOS), ED revisits and rehospitalizations for AHF, and mortality using the Wilcoxon rank-sum tests and linear regression or Pearson chi-square test and logistic regression, as appropriate.ResultsThe median age of the 187 patients was 64, and 50% were African-American. There were 5.9% of patients with a FeNa less than 0.2%, 17.1% had urinary sodium less than 50 meq/L, and 10.7% had a urinary Na/K ratio <1.0. The three definitions identified significantly different patients with very little overlap (p < 0.02 for all comparisons). There were 37 (19.8%) patients who were readmitted to the ED or hospital or died within 30 days of ED evaluation. Patients with spot urinary sodium less than 50 meq/L were more likely to be readmitted (p = 0.03).ConclusionsThe patient proportion with poor natriuresis and DR varies depending on the definition used. Early ED therapy would be impacted at different rates if clinical decisions are made based on these definitions. These findings need to be further explored in a prospective ED-based study.Trial registrationClinicalTrials.gov, NCT00508638.

Dataset Information

Spironolactone in Acute Heart Failure Patients With Renal Dysfunction and Risk Factors for Diuretic Resistance: From the ATHENA-HF Trial.

Publications

Spironolactone in Acute Heart Failure Patients With Renal Dysfunction and Risk Factors for Diuretic Resistance: From the ATHENA-HF Trial.

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