Efficacy and safety of dapagliflozin according to aetiology in heart failure with reduced ejection fraction: insights from the DAPA-HF trial

Butt, J. H. et al. (2021) Efficacy and safety of dapagliflozin according to aetiology in heart failure with reduced ejection fraction: insights from the DAPA-HF trial. European Journal of Heart Failure, 23(4), pp. 601-613. (doi: 10.1002/ejhf.2124) (PMID:33594755)

Abstract

Aims: We examined the efficacy and safety of dapagliflozin, compared with placebo, according to aetiology in patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in the Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure trial (DAPA‐HF). Methods and results: Aetiology was investigator‐reported and categorized as ischaemic or non‐ischaemic. The primary outcome was the composite of an episode of worsening HF or cardiovascular death. A total of 4,744 patients were randomised in DAPA‐HF, of whom 2,674 (56.4%) patients had an ischaemic aetiology. Participants with an ischaemic aetiology had a higher risk of cardiovascular mortality (hazard ratio [HR] 1.35 [95%CI 1.13‐1.63]), but lower risk of HF hospitalisation (0.83 [0.70‐0.98]) than non‐ischaemic patients. Compared with placebo, dapagliflozin reduced the risk of worsening HF or cardiovascular death to a similar extent in both patients with ischaemic and non‐ischaemic aetiology (HR 0.77 [95%CI 0.65‐0.92] and 0.71 [0.58‐0.87], respectively, P for interaction=0.55). Consistent benefits were observed for the components of the primary outcome and all‐cause mortality. Dapagliflozin, as compared with placebo, increased the proportion of patients with an improvement of KCCQ‐TSS of ≥5 points (P for interaction=0.32) and decreased the proportion with a deterioration in KCCQ‐TSS of ≥5 points (P for interaction=0.76), irrespective of aetiology. Study drug discontinuation and serious adverse events were similar according to treatment groups, irrespective of aetiology. Conclusions: Dapagliflozin reduced the risk of worsening HF and death, and improved symptoms, similarly in patients with ischaemic and non‐ischaemic aetiology. In addition, dapagliflozin was safe and well‐tolerated, irrespective of aetiology.

• Item Type: Articles
• Additional Information: The DAPA‐HF trial was funded by AstraZeneca. Prof. McMurray is supported by British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Butt, Mr Jawad and Docherty, Dr Kieran and Petrie, Professor Mark and McMurray, Professor John and Jhund, Professor Pardeep
• Authors: Butt, J. H., Nicolau, J. C., Verma, S., Docherty, K. F., Petrie, M. C., Inzucchi, S. E., Schou, M., Kosiborod, M. N., Langkilde, A. M., Martinez, F. A., Ponikowski, P., Sabatine, M. S., Sjöstrand, M., Solomon, S. D., Bengtsson, O., Jhund, P. S., McMurray, J., and Køber, L.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: European Journal of Heart Failure
• Publisher: Wiley
• ISSN: 1388-9842
• ISSN (Online): 1879-0844
• Published Online: 16 February 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in European Journal of Heart Failure 23(4): 601-613
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
303944		BHF Centre of Excellence	Rhian Touyz	British Heart Foundation (BHF)	RE/18/6/34217	CAMS - Cardiovascular Science