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

16 JULY 2019

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

Shweta Bansal, MD; Kristina Munoz, BS; Sonja Brune, MSN; Steven Bailey, MD; Anand Prasad, MD; Chakradhar Velagapudi, PhD

Background: Resistance to loop diuretics occurs frequently in patients with acute decompensated heart failure (1), and secondary hyperaldosteronism plays a major role (2). Aldosterone antagonists are a standard of care in heart failure but are commonly used at low, nonnatriuretic doses to avoid hyperkalemia (3, 4).

Objective: To examine whether the addition of high-dose spironolactone could be safe and effective in selected patients with acute decompensated heart failure.

Methods: We did a prospective, single-center, nonrandomized trial with informed consent, institutional review board approval, and prior registration (ClinicalTrials.gov: NCT02823626). Eligible patients were recently hospitalized for heart failure with reduced or preserved ejection fraction and at least 1 symptom (dyspnea, orthopnea, or peripheral swelling) and 1 sign (rales, edema, or radiographic pulmonary edema) of hypervolemia. We excluded patients with acute coronary syndrome, active infection, end-stage liver disease, an estimated glomerular filtration rate less than 30 mL/min/1.73 m2, or a serum potassium level of 5.5 mmol/L or higher; pregnant patients; and those receiving spironolactone at a dosage higher than 25 mg/d. We weighed patients in their hospital gowns every day using the same scale, and we asked them to indicate their dyspnea level on a 7-point Likert scale.

We identified consecutive patients who lost less than 0.5 kg weight per day despite receiving intravenous furosemide at a dosage of at least 160 mg/d (with at least 1 dose >80 mg) and patients who, at 48 hours after admission and regardless of diuretic dose, lost less than 0.5 kg per day or had no change in dyspnea. For these patients, we added spironolactone, 100 mg/d (and patiromer, 8.4 g/d, if the serum potassium level was >4.3 mmol/L without potassium supplements). For patients already receiving spironolactone, 25 mg/d, we increased the dosage to 100 mg/d. The next day, we increased the dosage to 200 mg/d if participants lost less than 0.5 kg per day and had an increase in serum creatinine level of less than 26.52 µmol/L (0.30 mg/dL).

Results: Of the 316 patients who were potential study participants, 180 responded to loop diuretics before the study team could determine their eligibility (usually because of emergency overnight admissions), 89 met exclusion criteria, and 47 enrolled in the study. Of these, 20 met criteria for high-dose spironolactone and one subsequently withdrew because of mechanical ventilation. The Table describes baseline characteristics.

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