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Effects of SGLT2 inhibitor on clinical outcomes in acute decompensated HF patients

Literature - Damman K, Beusekamp JC, Boorsma EM et al., - Eur J Heart Fail. 2020, doi: 10.1002/ejhf.1713.

Introduction and methods

The DAPA-HF study recently showed that the SGLT2 inhibitor dapagliflozin reduced the risk of HF hospitalization and CV death in patients with established chronic HF with reduced ejection fraction (HFrEF), with and without diabetes [1]. The beneficial effects can partly be explained by the diuretic/natriuretic effects of SGLT2 inhibitors, but other mechanisms such as direct cardiometabolic and renal enhancing effects have also been proposed [2-4]. Unlike chronic HF, there is no established therapy for acute HF to improve clinical outcomes [5]. Acute (decompensated) HF has a post-discharge mortality and rehospitalization risk of 20-30% in the first 3 to 6 months. Many patients are discharged with residual congestion, despite treatment with loop diuretics [6]. Worsening renal function and renal failure are common in patients with acute HF and are related to an impaired outcome when the diuretic response is poor [7,8]. Until now, no data on the effects of SGLT2 inhibitors were available in patients with acute HF.

EMPA-RESPONSE-AHF was an investigator initiated, randomized, placebo-controlled, double-blind, parallel group, multicenter pilot study in patients admitted for acute (decompensated) HF. A total of 80 acute HF patients (with and without T2DM) were randomized in a 1:1 ratio within 24h of presentation to the hospital to receive either empagliflozin 10 mg/day or matched placebo for 30 days. Acute HF was defined as all of the following: dyspnea at rest or minimal exertion, signs of congestion, BNP ≥350 pg/mL or NT-proBNP ≥2000 pg/mL and treated with loop diuretics at screening. Mean age was 76 years, 33% were female, 47% had de novo acute HF, mean LVEF was 36%, and median NT-proBNP was 5236 pg/mL. One third of patients had T2DM. Patients were followed until day 60.

Primary endpoints were change in dyspnea visual analogue scale(VAS) from baseline to day 4, diuretic response (defined as weight kg/[(total intravenous dose)/40mg]+[(total oral dose)/80mg)] furosemide or equivalent loop diuretic dose) through day 4, length of hospital stay, and percentage change in NT-proBNP from baseline to day 4. Secondary endpoints were worsening HF, all-cause death and/or HF readmission through day 30 and day 60 as part of safety assessment.

Main results

  • No significant differences between the empagliflozin and placebo group were found in primary outcomes including change in VAS dyspnea, diuretic response (weight loss per 40 mg furosemide), reduction in NT-proBNP, and length of hospital stay.
  • A significant reduction was observed in the combined secondary endpoint of in-hospital worsening HF, death and/or hospital readmission at day 60 in the empagliflozin group in comparison with the placebo group (4 [10%] vs. 13 [33%], P=0.014).
  • In a subset of patients of whom data on urinary output and net fluid loss were available, patients on empagliflozin had greater cumulative urine output until day 4 compared with patients on placebo (difference 3449 mL, 95%CI 578–6321 mL, P=0.02, n=28) and net fluid loss was greater in patients on empagliflozin compared to patients on placebo (difference 2701 mL, 95%CI -586 to 8988 mL, P=0.10, n=25).
  • A significant lower number of CV adverse event (AEs) were observed in the empagliflozin group compared with placebo (9 vs. 17 events, P=0.046). No difference in total and serious AEs were seen between the two groups.


This randomized pilot study showed that the SGLT2 inhibitor empagliflozin did not improve dyspnea, NT-proBNP, diuretic response and length of hospital stay in patients with acute (decompensated) HF. However, empagliflozin was associated with a greater urinary output and a reduction in a combined outcome of worsening HF, death and/or rehospitalization for HF at 60 days. Empagliflozin use in patients with acute (decompensated) HF is safe and was well tolerated. Large randomized clinical trials are needed to study the role of SGLT2 inhibitors in patients with acute HF.


1. McMurray JJ, Solomon SD, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Belohlavek J, Bohm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukat A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CE, Merkely B, Nicolau JC, O’Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DL DM, Docherty KF, Jhund PS, Bengtsson O, Sjostrand M, Langkilde AM; DAPA-HF Trial Committees and Investigators. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med 2019;381:1995–2008.

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Find this article online on Eur J Heart Fail.

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Schedule25 May 2024