Physicians' Academy for Cardiovascular Education

Effects of SGLT2i on renal function in patients hospitalized for acute HF

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

Literature - Voors AA, Damman K, Teerlink JR, et al - Eur J Heart Fail. 2022 Sep 6. doi: 10.1002/ejhf.2681.

Introduction and methods

Background

The EMPULSE trial showed that treatment with the SGLT2i empagliflozin for 90 days results in a statistically significant clinical benefit in patients hospitalized for acute HF, compared with placebo [1]. In patients with chronic HF, SGLT2i cause a decrease in eGFR of 2-4 ml/min per 1.73 m2 in the first weeks of treatment, followed by a slower decline in eGFR over time, compared with placebo [2-7]. However, the effect of SGLT2i on renal function is largely unknown in patients hospitalized for acute HF.

Aim of the study

The aim of this post hoc analysis of data from the EMPULSE trial of patients hospitalized for acute HF was twofold. First, the study examined the effect of empagliflozin on renal function, sodium and potassium levels and the occurrence of renal and urinary adverse events. Second, the study examined whether renal function at baseline affected the clinical benefit of empagliflozin.

Methods

The researchers conducted a post hoc analysis of data from the EMPULSE trial. This multicenter, double-blind, placebo-controlled phase 3 trial included 530 adults hospitalized for acute HF (de novo or decompensated chronic HF), with or without DM2 and regardless of ejection fraction. Participants were randomized (1:1) between once daily empagliflozin 10 mg (n=265) or placebo (n=265) for 90 days as early as possible after clinical stabilization, but no earlier than 24 hours and no later than 5 days after admission. Inclusion criteria were dyspnea on exertion or at rest and at least 2 of the following findings: congestion on chest radiograph, rales on auscultation of the lungs, clinically relevant edema or increased jugular venous pressure. Patients with an eGFR<20 ml/min per 1.73 m2 were excluded from participation. Renal function (eGFR) and sodium and potassium levels were measured at baseline and on days 15, 30 and 90 of treatment. Patients were divided into the following 3 subgroups based on eGFR at baseline: <45, ≥45 and <60, and >60 ml/min per 1.73 m2.

Outcomes

The researchers evaluated the effect of empagliflozin on eGFR and sodium and potassium levels over time and the influence of eGFR at baseline on the primary outcome. The primary outcome was clinical benefit, defined as a hierarchical composite of (i) time death from any cause, (ii) number of HF events, (iii) time to first HF event or (iv) a difference in KCCQ-TSS of 5 or more points from baseline to day 90 of treatment. Clinical benefit was assessed using a win ratio. Renal and urinary adverse events were also assessed.

Main results

Renal function

Sodium and potassium levels

Renal and urinary adverse events

Conclusion

This post hoc analysis of data from the EMPULSE trial showed that in patients hospitalized for acute HF, treatment with empagliflozin resulted in a modest, not statistically significant decline in renal function after 15 days, compared with placebo. After 90 days, this difference had virtually disappeared. The clinical benefit of empagliflozin was independent of renal function at baseline and the frequency of renal and urinary adverse events was similar in both groups.

References

Show references

Find this article online at Eur J Heart Fail.

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