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Effect of Early Empagliflozin in Acute Heart Failure
Quick Takes
- In a randomized trial of 60 patients with acute decompensated heart failure, 25 mg of empagliflozin started within 12 hours of hospitalization increased cumulative urine output by 25% compared to placebo in addition to standard diuretic therapy over 5 days.
- Dose of loop diuretic needed in the empagliflozin group was lower compared to placebo with a higher eGFR at day 30 of hospitalization and greater change in NYHA class.
- Uric acid levels were lower in the empagliflozin group.
Study Questions:
What is the effect of early initiation of a sodium-glucose cotransporter-2 (SGLT-2) inhibitor within the first 12 hours of presentation with acute decompensated heart failure (ADHF)?
Methods:
This was a randomized controlled trial of empagliflozin 25 mg daily versus placebo started within 12 hours of hospitalization for 5 days in addition to standard diuretic therapy. Adults with ADHF with a B-type natriuretic peptide (BNP) of >100 pg/mL or N-terminal pro-BNP (NT-proBNP) >300 pg/mL, with or without diabetes, were included. Primary outcomes included total urine output summed over 5 days. Secondary markers included worsening renal function (increase in creatinine of >0.3 mg/dL, doubling of creatinine of renal replacement therapy), trajectory of estimated glomerular filtration rate (eGFR), cystatin C, and changes in baseline kidney function.
Results:
A total of 60 patients were enrolled with a mean age of 75 ± 10 years and 38% were women. Overall, 21% had an ejection fraction <30% and mean eGFR at baseline was 60 mL/min/1.73 m2. Cumulative urine output over 5 days was greater in the empagliflozin group by 25% compared to placebo. Mean NT-proBNP showed a larger decline from baseline in the empagliflozin group. Dose of loop diuretics used was lower in the empagliflozin group. There was no change in eGFR between the two groups at day 5 but at day 30, patients in the placebo group had a lower eGFR than patients on empagliflozin. Other markers of renal dysfunction were no different between the two groups. Patients in the empagliflozin group had a greater change in NYHA class from baseline to day 5 and until hospital discharge. No significant adverse events occurred in the empagliflozin group. Uric acid levels were lower in the empagliflozin group.
Conclusions:
Use of empagliflozin 25 mg within 12 hours of hospitalized ADHF patients was associated with a 25% increase in cumulative urine output in 5 days with need for lesser loop diuretic. Empagliflozin use was associated with a larger decrease in NT-proBNP levels and improved NYHA class with a better eGFR at day 30 compared to placebo.
Perspective:
Decongestive therapy with diuretics forms the mainstay of therapy for patients hospitalized with ADHF. Despite several advances in neurohormonal blockade, no effective decongestive therapies have been identified apart from loop diuretics. Loop diuretics in turn are associated with several issues such as worsening renal function and gout. This randomized trial is the first to show that early addition of a SGLT-2 inhibitor within 12 hours of hospitalization helps lower the dose needed for loop diuretics while increasing the cumulative urine output. In addition, the study confirms previously noted renal protection offered by these agents in the acute setting as well with NYHA class too. Notably, uric acid levels were lower in the empagliflozin group, suggesting that these agents may be less likely to precipitate acute gouty attacks. While this study is small in size and does not report hard endpoints like mortality and hospitalization, it is notable that a large difference in urine output and NT-proBNP levels was seen with such a small number of patients.
Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers
Keywords: Creatinine, Cystatin C, Diabetes Mellitus, Diuresis, Diuretics, Glomerular Filtration Rate, Gout, Heart Failure, Kidney Diseases, Natriuretic Peptide, Brain, Patient Discharge, Renal Insufficiency, Chronic, Secondary Prevention, Sodium Potassium Chloride Symporter Inhibitors, Sodium-Glucose Transporter 2 Inhibitors, Stroke Volume, Uric Acid
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