Physicians' Academy for Cardiovascular Education

No need to stop SGLT2i therapy when early eGFR decrease occurs in HFrEF patients

Early changes in estimated glomerular filtration rate post-initiation of empagliflozin in EMPEROR-Reduced

Literature - Zannad F, Ferreira JP, Gregson J, et al. - Eur J Heart Fail. 2022 Jun 16 [Online ahead of print]. doi: 10.1002/ejhf.2578

Introduction and methods


In patients with HFrEF, SGLT2i treatment slows the rate of eGFR decline compared with placebo, starting from week 4 after treatment initiation [1-4]. However, SGLT2is may induce an initial eGFR decrease, possibly due to acute intraglomerular pressure reduction [5-9]. This decrease may tempt clinicians to stop or withhold the therapy, but is that justified?

Aim of the study

The authors aimed to describe the occurrence, characteristics, determinants, and prognostic significance of early eGFR changes in HFrEF patients who had been treated with empagliflozin or placebo in the EMPEROR-Reduced (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction) trial.


The EMPEROR-Reduced trial was a multinational, randomized, double-blind, parallel-group, placebo-controlled, event-driven, phase 3 study in which 3730 patients with chronic HF (NYHA functional class II–IV) and LVEF ≤40% were randomized to empagliflozin 10 mg daily or placebo, in addition to their usual therapy (including HF treatment) [10,11]. In this secondary analysis, 3547 patients (95%) were included who had received at least one dose of the study drug and for whom eGFR measurements at randomization and week 4 were available. Median follow-up duration was 16 months.

The researchers categorized the percent (%) eGFR change in the early post-initiation period (from randomization to week 4) into tertiles in each treatment group separately and used landmark analyses (with landmark at week 4) to study the associations of % eGFR change with outcomes.


The primary endpoint was the composite of adjudicated CV death and HF hospitalization (analyzed as time to first event). In addition, CV death, all-cause mortality, and a composite renal outcome (i.e., need for chronic dialysis or renal transplant; sustained eGFR decrease ≥40%; or sustained eGFR <10–15 mL/min per 1.73 m2, depending on baseline eGFR) were analyzed.

The prespecified safety assessment focused on the occurrence of acute kidney injury or acute renal failure, until 7 days following discontinuation of the study medication.

Main results

eGFR change at week 4

Association of early eGFR change with outcomes



HFrEF patients showed a mild eGFR decrease in the first 4 weeks after initiating empagliflozin treatment compared with placebo, but this was not associated with adverse CV or renal outcomes. The authors stress that clinicians should not be concerned about early eGFR changes following empagliflozin initiation. They do not recommend to routinely monitor eGFR in the first month and advise to leave this decision to the discretion of the treating physician.


Show references

Find this article online at Eur J Heart Fail.

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