High-Dose Spironolactone When Patients With Acute Decompensated Heart Failure Are Resistant to Loop Diuretics

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Clinical Question

In patients with heart failure exacerbations that don't respond to loop diuretics for >48 hours, does the addition of high-dose spironolactone improve diuresis?

Bottom Line

In this single-center pilot study, the addition of high-dose spironolactone (100mg to 200mg daily) significantly improved diuresis in loop diuretic resistant patients.

Major Points

In 2016, the ATHENA-HF found that the addition of high-dose spironolactone (100mg daily) to standard care for 96 hours did not significantly improve NT-proBNP level or overall diuresis. However, this study was criticized for including patients who responded to loop diuretics and not stratifying patients into high risk and low risk cohorts. This pilot study looked only at high risk patients who were clinically found to be resistant to loop diuretics and found that their addition in this setting significantly improved diuresis. While results are preliminary, these results are promising and suggest the need for a large randomized controlled trial.




  • Single center, un-blinded, non-randomized, prospective trial
  • N=47
    • Loop responsive: 27
    • Loop resistant: 20
  • Setting: 1 center in the United States
  • Mean follow-up: duration of hospitalization
  • Analysis: Intention-to-treat
  • Primary outcome: weight loss


Inclusion Criteria

  • Recent hospitalization for heart failure with reduced or preserved ejection fraction
  • Lost less than 0.5kg per day after receiving at least 160mg per day of furosemide
  • Lost less than 0.5kg per day and had no change in Likert dyspnea score after receiving any dose of loop diuretic

Exclusion Criteria

  • Potassium 5.5 or greater
  • eGFR 30 or less
  • Active infection
  • Acute coronary syndrome
  • Prescribed spironolactone at dose higher than 25mg per day

Baseline Characteristics

  • Mean age: 62
  • Percent male: 60%
  • Race
    • Non-hispanic white: 35%
    • Non-hispanic black: 15%
    • Hispanic: 50%
  • NYHA:
    • III/IV: 100%
    • II/I: 0%
  • Comorbidities
    • Chronic kidney disease (eGFR <60): 65%
    • Coronary artery disease: 55%
    • Hypertension: 75%
    • Diabetes: 45%


  • All eligible participants were screened for loop sensitivity:

    • 180 immediately excluded for responding to loop diuretics immediately
    • 42 eligible patients refused to enroll in study
    • 27 eligible patients did not meet criteria for high-dose spironolactone therapy
    • 20 eligible patients met criteria for high-dose spironolactone therapy
  • Eligible patients who met criteria for high-dose spironolactone therapy were given 100mg spironolactone daily until symptom resolution.
  • Eligible patients who lost <0.5kg and had Cr increase of <0.3 on 100mg spironolactone were given 200mg daily daily until symptom resolution.
  • There was no control group.


Primary Outcomes


Secondary Outcomes

Likert dyspnea score improved by >3 by day 4
14 of 19 (73.7%)
Potassium >5.5 after initiation of high-dose spironolactone therapy
0 of 19 (0.0%)
Creatinine rise >0.3 after initiation of high-dose spironolactone therapy
2 of 19 (12.5%)

Subgroup Analysis


Adverse Events


This paper is an observational study and is limited by its small size, lack of a control group, and being unblinded. A randomized controlled trial is necessary to assess the wider application of this study's results.


There were no significant conflicts of interest reported by the authors.

Further Reading

1. https://annals.org/aim/fullarticle/2738163/high-dose-spironolactone-when-patients-acute-decompensated-heart-failure-resistant

2. https://jamanetwork.com/journals/jamacardiology/fullarticle/10.1001/jamacardio.2017.2198