Schulze PC, Bogoviku J, Westphal J, et al. Effects of Early Empagliflozin Initiation on Diuresis and Kidney Function in Patients With Acute Decompensated Heart Failure (EMPAG-HF). Circulation. 2022 Jul 26;146(4):289-298. doi: 10.1161/CIRCULATIONAHA.122.059038. Epub 2022 Jun 29. (Original study)

BACKGROUND: Effective diuretic regimens using loop diuretics in patients with acute decompensated heart failure are often limited by the development of worsening kidney function. Sodium-glucose cotransporter-2 inhibitors induce glucosuria and sodium excretion with nephroprotective effects in patients with stable heart failure but their role in acute decompensated heart failure is unclear.

METHODS: In this single-center, prospective, double-blind, placebo-controlled, randomized study, we randomly assigned patients with acute decompensated heart failure to empagliflozin 25 mg daily or placebo in addition to standard decongestive treatments that included loop diuretics. The primary end point was cumulative urine output over 5 days. Secondary end points included diuretic efficiency, dynamics in markers of kidney function and injury, and NT-proBNP (N-terminal pro-B-type natriuretic peptide).

RESULTS: Sixty patients were randomized within 12 hours of hospitalization for acute decompensated heart failure. Addition of empagliflozin daily to standard medical treatment of acute decompensated heart failure resulted in a 25% increase in cumulative urine output over 5 days (median 10.8 versus 8.7 L mL in placebo, group difference estimation 2.2 L [95% CI, 8.4 to 3.6]; P=0.003). Empagliflozin increased diuretic efficiency compared with placebo (14.1 mL urine per milligram furosemide equivalent [95% CI, 0.6-27.7]; P=0.041) without affecting markers of renal function (estimated glomerular filtration rate, 51±19 versus 54±17 mL/min per 1.73 m²; P=0.599) or injury (total urinary protein, 492±845 versus 503±847 mg/g creatinine; P=0.975; and urinary a1-microglobulin, 55.4±38.6 versus 31.3±33.6 mg/g creatinine; P=0.066) with more pronounced decrease in NT-proBNP in the empagliflozin group compared with placebo (-1861 versus -727.2 pg/mL after 5 days; quotient in slope, 0.89 [95% CI, 0.83-0.95]; P<0.001). There were no differences in the incidence of safety events between groups.

CONCLUSIONS: Early addition of empagliflozin to standard diuretic therapy increases urine output without affecting renal function in patients with acute decompensated heart failure.

REGISTRATION: URL: https://www.

CLINICALTRIALS: gov; Unique identifier: NCT04049045.

Discipline Area Score
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Cardiology 6 / 7
Nephrology 6 / 7
Internal Medicine 6 / 7
Comments from MORE raters

Cardiology rater

SGLT2I would be effective meds for acute decompensated HF with or without DM. The meds might cause additional diuresis to control congestive HF. If it would be enough to stabilize HF and diuresis, we would choose this as an early initiation.

Cardiology rater

As a Consultant in Internal Medicine, this article will very much impact my current practice if a few more studies come up with consistent results. This is a very well conducted RCT.

General Internal Medicine-Primary Care(US) rater

As an academic hospitalist, this article has tremendous relevance and is very exciting. As noted by the authors, this is the first really novel treatment for CHF to come along in a while. The potential impact of being able to improve CHF care while minimizing side effects and AKI has a huge impact. The limitations of the study are noted and addressed by the authors. The small sample size is somewhat concerning, but the parameters for the study were tight and the results still reached statistical significance. I feel this will spur more and larger studies regarding early use of SGLT2 inhibitors in acute CHF. Another major concern, at least currently, is the cost of the drugs, but this is somewhat of a barrier also for entresto and practitioners have found some creative workarounds for it. I am hopeful that more and larger trials substantiate the findings here.

Internal Medicine rater

Why didn't patients' weight change with more fluid loss?

Nephrology rater

This article will produce a new era for treating patients with acute decompensated heart failure.
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