Efficacy of dapagliflozin on renal function and outcomes in patients with heart failure with reduced ejection fraction: results of DAPA-HF

Jhund, P. S. et al. (2021) Efficacy of dapagliflozin on renal function and outcomes in patients with heart failure with reduced ejection fraction: results of DAPA-HF. Circulation, 143(4), pp. 289-309. (doi: 10.1161/CIRCULATIONAHA.120.050391) (PMID:33040613) (PMCID:PMC7834909)

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Abstract

Background: Many patients with heart failure and reduced ejection fraction (HFrEF) have chronic kidney disease (CKD) which complicates pharmacological management and is associated with worse outcomes. We assessed the safety and efficacy of dapagliflozin in patients with HFrEF, according to baseline kidney function, in the Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). We also examined the effect of dapagliflozin on kidney function after randomization. Many patients with heart failure and reduced ejection fraction (HFrEF) have chronic kidney disease (CKD) which complicates pharmacological management and is associated with worse outcomes. We assessed the safety and efficacy of dapagliflozin in patients with HFrEF, according to baseline kidney function, in the Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). We also examined the effect of dapagliflozin on kidney function after randomization. Methods: HFrEF patients with or without type 2 diabetes and an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73m 2 were enrolled in DAPA-HF. We calculated the incidence of the primary outcome (CV death or worsening HF) according to eGFR category at baseline (<60 and ≥60 ml/min/1.73m 2 ) as well as using eGFR at baseline as a continuous measure. Secondary cardiovascular outcomes and a pre-specified composite renal outcome (≥ 50% sustained decline eGFR, end stage renal disease (ESRD) or renal death) were also examined, along with decline in eGFR over time. Results: Of 4742 with a baseline eGFR, 1926 (41%) had eGFR <60 ml/min/1.73m 2 . The effect of dapagliflozin on the primary and secondary outcomes did not differ by eGFR category or examining eGFR as a continuous measurement. The hazard ratio (95% confidence interval (CI)) for the primary endpoint in patients with CKD was 0.71 (0.59, 0.86) vs. 0.77 (0.64, 0.93) in those with an eGFR ≥60 ml/min/1.73m 2 (interaction p=0.54). The composite renal outcome was not reduced by dapagliflozin (HR=0.71, 95% CI 0.44, 1.16; p=0.17) but the rate of decline in eGFR between day 14 and 720 was less with dapagliflozin, -1.09 (-1.41, -0.78) vs. placebo -2.87 (-3.19, -2.55) ml/min/1.73m 2 per year (p<0.001). This was observed in those with and without type 2 diabetes (p for interaction=0.92) Conclusions: Baseline kidney function did not modify the benefits of dapagliflozin on morbidity and mortality in HFrEF and dapagliflozin slowed the rate of decline in eGFR, including in patients without diabetes. Clinical Trial Registration: https://clinicaltrials.gov Unique Identifier: NCT03036124

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Docherty, Dr Kieran and McMurray, Professor John and Jhund, Dr Pardeep and Kober, Professor Lars
Authors: Jhund, P. S., Solomon, S. D., Docherty, K. F., Heerspink, H. J.L., Anand, I. S., Böhm, M., Chopra, V., de Boer, R. A., Desai, A. S., Ge, J., Kitakaze, M., Merkely, B., O'Meara, E., Schou, M., Tereshchenko, S., Verma, S., Vinh, P. N., Inzucchi, S. E., Køber, L., Kosiborod, M. N., Martinez, F. A., Ponikowski, P., Sabatine, M. S., Bengtsson, O., Langkilde, A. M., Sjöstrand, M., and McMurray, J. J.V.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Circulation
Publisher:American Heart Association
ISSN:0009-7322
ISSN (Online):1524-4539
Published Online:12 October 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Circulation 143(4): 289-309
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceRhian TouyzBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science