Physicians' Academy for Cardiovascular Education

SGLT2 inhibition leads to early decongestion and clinical benefit in acute HF

Impact of empagliflozin on decongestion in acute heart failure: the EMPULSE trial

Literature - Biegus J, Voors AA, Collins SP, et al. - Eur Heart J. 2022 Oct 18;ehac530. doi: 10.1093/eurheartj/ehac530

Introduction and methods

Background

In patients with acute HF (AHF), residual congestion at hospital discharge contributes to readmission and predicts poor outcome [1]. Therefore, effective and safe decongestion remains the main goal of AHF therapy [2-4]. Although diuretics are the first-line treatment for AHF patients, their use be limited due to, among others, impaired kidney function or poor response to the particular diuretic [5]. As SGLT2i tend to facilitate decongestion in patients with chronic HF [6,7], the question is whether they can achieve the same decongestive efficacy in AHF.

Previously, the EMPULSE (EMPagliflozin in patients hospitalized with acUte heart faiLure who have been StabilizEd) trial showed that early treatment with the SGLT2i empagliflozin resulted in a statistically significant and clinically meaningful benefit within 90 days in hospitalized AHF patients compared with placebo [8,9].

Aim of the study

The aim of the study was to evaluate the effect of empagliflozin on several prespecified decongestion-related endpoints in the EMPULSE trial and to examine whether decongestion itself was associated with clinical benefit at day 90.

Methods

The EMPULSE trial was a multinational, multicenter, randomized, double-blind study in which 530 patients hospitalized for AHF were randomized, after initial stabilization, to treatment with empagliflozin 10 mg once daily or placebo for 90 days. Inclusion criteria were: hospital admission with primary diagnosis of AHF, treatment with minimum dose of 40 mg of intravenous furosemide or equivalent, dyspnea (exertional or at rest), and ≥2 of 4 signs of congestive HF. One of the key exclusion criteria was AHF primarily triggered by pulmonary embolism, CVA, or acute MI.

The primary endpoint of the EMPULSE trial was clinical benefit as measured by the stratified win ratio. The order and components of the primary endpoint were: time to all-cause death, number of HF events (including HF hospitalizations, urgent HF visits, and unplanned outpatient visits), time to first HF event, and ≥5-point difference in change from baseline in the Kansas City Cardiomyopathy Questionnaire – total symptom score at day 90.

Outcomes

For the current analysis, changes from baseline to days 15, 30, and 90 of treatment in the following decongestion-related endpoints were evaluated: weight loss, weight loss adjusted per mean daily loop diuretic dose, area under the curve (AUC) of change from baseline in log-transformed NT-proBNP level (over 30 days of treatment), hemoconcentration (measured as hematocrit changes), and clinical congestion score.

Main results

Changes in decongestion-related endpoints

Effect of body weight loss or hematocrit change on clinical benefit at day 90

Conclusion

In patients hospitalized for AHF, empagliflozin treatment initiated after initial in-hospital stabilization resulted in early (at day 15), clinically meaningful, and sustained (present at day 90) decongestion compared with placebo. The magnitude of the decongestion (as proxied by more body weight loss) was associated with a clinical benefit at day 90. According to the authors, their “findings suggest that empagliflozin added to standard therapy improves diuretic efficacy,” which becomes evident at day 15 and is sustained until day 90.

References

Show references

Find this article online at Eur Heart J.

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