Renal effects of empagliflozin in patients hospitalized for acute heart failure: from the EMPULSE trial

Abstract

The sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin improved clinical outcomes in patients hospitalized for acute heart failure. In patients with chronic heart failure, SGLT2 inhibitors cause an early decline in estimated glomerular filtration rate (eGFR) followed by a slower eGFR decline over time than placebo. However, the effects of SGLT2 inhibitors on renal function during a hospital admission for acute heart failure remain largely unknown.

October 2022 at a glance: focus on clinical trials

“…Similarly, in the EMPULSE trial, including patients hospitalized for acute HF with an eGFR >20 ml/min/1.73 m 2 , empagliflozin caused an initial decline in eGFR of –2 ml/min/1.73 m 2 at day 15 compared to placebo that was no longer evident at day 90. The clinical benefit of empagliflozin was independent of baseline eGFR 14 …”

“…The clinical benefit of empagliflozin was independent of baseline eGFR. 14 Liver dysfunction is a marker of more severe HF and an independent predictor of poor prognosis. 15 In the Dapagliflozin And Prevention of Adverse outcomes in Heart Failure (DAPA-HF) trial, patients with the highest bilirubin tertile had more severe HFrEF…”

Inhibiting the proximal nephron in acute heart failure – emerging data on kidney safety and efficacy

“…In this post-hoc analysis of the EMPULSE trial, in which 530 patients with AHF were randomized to either placebo or empagliflozin 10 mg, the kidney safety of empagliflozin was assessed. 3 It is important to remember that the patients in the EMPULSE trial were randomized within a median of 3 days after the AHF admission, while still being in the hospital, which is faster as in the SOLOIST-WHF trial (median of 2 days after discharge of the AHF hospitalization). 4 This thus implies a patient population at risk for changes in creatinine by having AHF, but also having undergone in-hospital treatment with loop diuretics.…”

“…Both the reassuring safety analyses from the EMPULSE and ADVOR trials generate the hope that these agents could potentially be combined from a kidney safety perspective. 3,5 Furthermore, the heart failure syndrome is an excellent example were true treatment successes are achieved when agents are combined targeting different pathophysiologic mechanisms. From a more pragmatic standpoint, taking into account the design of the ADVOR, EMPULSE, SOLOIST-WHF and the different SGLT2 inhibitors trials in chronic heart failure, SGLT2 inhibitor naïve patients with AHF could first be treated with acetazolamide (on top of high-dose loop diuretics) for 3 days (treatment phase of ADVOR trial) to efficiently achieve decongestion and shorten length of stay.…”

“…Keeping in mind these important renal physiologic aspects, in this issue of the Journal the analysis from Voors and colleagues offer much welcomed information on the safety of SGLT2 inhibitors in AHF. In this post‐hoc analysis of the EMPULSE trial, in which 530 patients with AHF were randomized to either placebo or empagliflozin 10 mg, the kidney safety of empagliflozin was assessed 3 . It is important to remember that the patients in the EMPULSE trial were randomized within a median of 3 days after the AHF admission, while still being in the hospital, which is faster as in the SOLOIST‐WHF trial (median of 2 days after discharge of the AHF hospitalization) 4 .…”