Efficacy and safety of dapagliflozin according to frailty in patients with heart failure: a prespecified analysis of the DELIVER trial

Butt, J. H. et al. (2022) Efficacy and safety of dapagliflozin according to frailty in patients with heart failure: a prespecified analysis of the DELIVER trial. Circulation, 146(16), pp. 1210-1224. (doi: 10.1161/CIRCULATIONAHA.122.061754) (PMID:36029465) (PMCID:PMC9815819)

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Background: Frailty is increasing in prevalence and because frail patients are often perceived to have a less favorable benefit/risk profile, they may be less likely to receive new pharmacological treatments. We investigated the efficacy and tolerability of dapagliflozin according to frailty status in patients with heart failure and mildly reduced and preserved ejection fraction randomized in DELIVER. Methods: Frailty was measured using the Rockwood cumulative deficit approach. The primary endpoint was time to a first worsening heart failure event or cardiovascular death. Results: Of the 6263 patients randomized, a Frailty Index (FI) was calculable in 6258. In total, 2,354 (37.6%) patients had class 1 frailty (FI <0.210, i.e., not frail), 2,413 (38.6%) were in class 2 (FI 0.211-0.310, i.e., more frail), and 1,491 (23.8%) had class 3 frailty (FI >0.311, i.e., most frail). Greater frailty was associated with a higher rate of the primary endpoint (per 100 person years): FI class 1, 6.3 (95% CI 5.7-7.1); class 2, 8.3 (7.5-9.1); and class 3, 13.4 (12.1-14.7), P<0.001. The effect of dapagliflozin (as a hazard ratio) on the primary endpoint from FI class 1 to 3 was: 0.85 (95% CI, 0.68-1.06); 0.89 (0.74-1.08); and 0.74 (0.61-0.91), respectively (Pinteraction=0.40). Although frailer patients had worse KCCQ scores at baseline, the improvement with dapagliflozin was greater than in less frail patients: placebo-corrected improvement in KCCQ-OSS at 4 months FI class 1, 0.3 (95% CI -0.9 to 1.4); class 2, 1.5 (0.3-2.7); and class 3, 3.4 (1.7-5.1) [Pinteraction=0.021]. Adverse reactions and treatment discontinuation, while more frequent in frailer patients, were not more common with dapagliflozin than placebo, irrespective of frailty class. Conclusions: In DELIVER, frailty was common and associated with worse outcomes. The benefit of dapagliflozin was consistent across the range of frailty studied. The improvement in health-related quality of life with dapagliflozin occurred early and was greater in patients with greater frailty.

Item Type:Articles
Additional Information:The DELIVER trial was funded by AstraZeneca. Profs McMurray and Jhund are supported by a British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217.
Glasgow Author(s) Enlighten ID:Butt, Mr Jawad and Jhund, Professor Pardeep and McMurray, Professor John
Authors: Butt, J. H., Jhund, P. S., Belohlávek, J., de Boer, R. A., Chiang, C.-E., Desai, A. S., Drożdzż, J., Hernandez, A. F., Inzucchi, S. E., Katova, T., Kitakaze, M., Kosiborod, M. N., Lam, C. S.P., Langkilde, A. M., Lindholm, D., Bachus, E., Martinez, F., Merkely, B., Petersson, M., Saraiva, J. F. K., Shah, S. J., Vaduganathan, M., Vardeny, O., Wilderäng, U., Claggett, B. L., Solomon, S. D., 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 (Online):1524-4539
Published Online:27 August 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Circulation 146(16): 1210-1224
Publisher Policy:Reproduced under a Creative Commons License

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