Dapagliflozin and diuretic use in patients with heart failure and reduced ejection fraction in DAPA-HF

Jackson, A. M. et al. (2020) Dapagliflozin and diuretic use in patients with heart failure and reduced ejection fraction in DAPA-HF. Circulation, 142(11), pp. 1040-1054. (doi: 10.1161/CIRCULATIONAHA.120.047077) (PMID:32673497) (PMCID:PMC7664959)

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Abstract

Background: In the DAPA-HF trial, the SGLT2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. We examined efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy following randomization to dapagliflozin or placebo. Methods: We examined the effects of study treatment in the following subgroups: no diuretic, diuretic dose equivalent to furosemide <40mg daily, 40mg daily and >40mg daily at baseline. We examined the primary composite endpoint of cardiovascular (CV) death or a worsening HF event, its components, all-cause death and symptoms. Results: Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on <40mg, 1365 (29.6%) on 40 mg and 1204 (26.1%) of patients were taking >40 mg. Compared with placebo, dapagliflozin reduced the risk of the primary endpoint across each of these subgroups: hazard ratio [HR]: 0.57 (95% CI 0.36-0.92), 0.83 (0.63-1.10), 0.77 (0.60-0.99) and 0.78 (0.63-0.97), respectively (P-interaction 0.61). The HR in patients taking any diuretic was 0.78 (0.68-0.90). Improvement in symptoms and treatment toleration was consistent across the diuretic subgroups. Diuretic dose did not change in most patients during follow-up and mean diuretic dose did not differ between the dapagliflozin and placebo group after randomization. Conclusions: The efficacy and safety of dapagliflozin was consistent across the diuretic subgroups examined in DAPA-HF. Clinical Trial Registration: DAPA-HF: ClinicalTrials.gov Identifier NCT03036124

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Docherty, Dr Kieran and Jackson, Dr Alice and Jhund, Dr Pardeep and Dewan, Dr Pooja and McMurray, Professor John and Kober, Professor Lars
Authors: Jackson, A. M., Dewan, P., Anand, I. S., Bělohlávek, J., Bengtsson, O., de Boer, R. A., Böhm, M., Boulton, D. W., Chopra, V. K., Demets, D. L., Docherty, K. F., Dukát, A., Greasley, P. J., Howlett, J. G., Inzucchi, S. E., Katova, T., Køber, L., Kosiborod, M. N., Langkilde, A. M., Lindholm, D., Ljungman, C. E.A., Martinez, F. A., O'Meara, E., Sabatine, M. S., Sjöstrand, M., Solomon, S. D., Tereshchenko, S., Verma, S., Jhund, P. S., and McMurray, J. J.V.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Circulation
Publisher:American Heart Association
ISSN:0009-7322
ISSN (Online):1524-4539
Published Online:16 July 2020
Copyright Holders:Copyright © 2020 American Heart Association, Inc.
First Published:First published in Circulation 142(11):1040–1054
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
301144The epidemiology of peripartum cardiomyopathy in a Western European country: An analysis of the Scottish population 1990-2016Pardeep JhundBritish Heart Foundation (BHF)FS/18/14/33330Institute of Cardiovascular & Medical Sciences
303944BHF Centre of ExcellenceRhian TouyzBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science