Physicians' Academy for Cardiovascular Education

SGLT2i improves CV outcomes in patients with HFmrEF or HFpEF regardless of kidney function

Dapagliflozin and Kidney Outcomes in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Prespecified Analysis of the DELIVER Randomized Clinical Trial

Literature - Mc Causland FR, Claggett BL, Vaduganathan M, et al. - JAMA Cardiol. 2023;8(1):56-65. doi: 10.1001/jamacardio.2022.4210.

Introduction and methods


CKD affects approximately 50% of patients with HFmrEF or HFpEF [1]. The presence of CKD increases the risk of CV death and hospitalization [2]. Recently, it was demonstrated that SGLT2i treatment with empagliflozin slowed the rate of kidney function decline in patients with HFmrEF and HFpEF [3]. The DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial previously reported that the SGLT2i dapagliflozin reduced the risk of CV death or worsening HF events among patients with HFmrEF or HFpEF [4].

Aim of the study

The current prespecified analysis of the DELIVER trail evaluated whether the effects of dapagliflozin vary according to baseline kidney function, and whether dapagliflozin reduces the rate of estimated glomerular filtration rate (eGFR) decline and kidney outcomes.


The DELIVER trail was an international, prospective, randomized, double-blind, placebo-controlled trial with 6263 patients with symptomatic HFmrEF/HFpEF (NYHA class II–IV HF symptoms, LVEF >40%, elevated NT-proBNP levels). Patients were randomly assigned to receive dapagliflozin at a dose of 10 mg once daily (3131 patients) or placebo (3132 patients). For the current analysis, data from 6262 patients with mean eGFR measurements were available.


The primary outcome was CV death or worsening of HF. Prespecified analyses included assessment whether baseline kidney function (eGFR of <45mL/min/1.73m², ≥45 to <60mL/min/1.73m², ≥60mL/min/1.73m² and eGFR as a continuous variable) modified the effect of dapagliflozin on the primary outcome. Prespecified exploratory outcomes were a change in eGFR and a post hoc composite kidney outcome (≥ 50% decline in eGFR from baseline; first eGFR <15 mL/min/1.73 m²; end-stage kidney disease; death from kidney causes). Safety outcomes were serious adverse events and adverse events that led to discontinuation of treatment.

Main results


This prespecified analysis of the DELIVER trial demonstrated that dapagliflozin reduced the risk of CV death or worsening of HF in patients with HFmrEF or HFpEF regardless of baseline kidney function. The incidence of the kidney composite outcome was low in the dapagliflozin group and in the placebo group, and dapagliflozin did not further reduce this incidence. Dapagliflozin slowed the long-term rate of decline in eGFR compared to placebo. SGLT2i treatment with dapagliflozin has beneficial effects on both cardiovascular outcomes as well as kidney function in patients with HFmrEF or HFpEF.


Show references

Find this article online at JAMA Cardiol.

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