Effect of dapagliflozin on outpatient worsening of patients with heart failure and reduced ejection fraction: a prespecified analysis of DAPA-HF

Docherty, K. F. et al. (2020) Effect of dapagliflozin on outpatient worsening of patients with heart failure and reduced ejection fraction: a prespecified analysis of DAPA-HF. Circulation, 142(17), pp. 1623-1632. (doi: 10.1161/CIRCULATIONAHA.120.047480) (PMID:32883108) (PMCID:PMC7580857)

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Background: In the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF), dapagliflozin, added to guideline-recommended therapies, reduced the risk of mortality and HF hospitalization. We examined the frequency and significance of episodes of outpatient heart failure-worsening, requiring augmentation of oral therapy, and the effects of dapagliflozin on these additional events. Methods: Patients in New York Heart Association (NYHA) functional class II-IV, with a left ventricular ejection fraction ≤40%, and elevation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) were eligible. The primary outcome was the composite of an episode of worsening heart failure (HF hospitalization or urgent HF visit requiring intravenous [IV] therapy) or cardiovascular (CV) death, whichever occurred first. An additional prespecified exploratory outcome was the primary outcome plus worsening HF symptoms/signs leading to initiation of new, or augmentation of existing, oral treatment. Results: Overall, 36% more patients experienced the expanded, compared with the primary, composite outcome. In the placebo group, 684/2371 (28.8%) patients, and 527/2373 (22.2%) participants in the dapagliflozin group, experienced the expanded outcome (HR 0.73, 0.65-0.82; P<0.0001); each component of the composite was reduced significantly by dapagliflozin. Over the median follow-up of 18.2 months, the number of patients needed to treat (NNT) with dapagliflozin to prevent one experiencing an episode of fatal or non-fatal worsening was 16. Among the 4744 randomized patients, the first episode of worsening was outpatient augmentation of treatment in 407 participants (8.6%), an urgent HF visit with IV therapy in 20 (0.4%), HF hospitalization in 489 (10.3%) and CV death in 295 (6.2%) patients. The adjusted risk of death from any cause (compared with no event) following an outpatient worsening was HR 2.67 (95%CI 2.03-3.52), after an urgent HF visit 3.00 (1.39-6.48) and after a HF hospitalization 6.21 (5.07-7.62). Conclusions: In DAPA-HF, outpatient episodes of HF worsening were common, of prognostic importance and reduced by dapagliflozin.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Docherty, Dr Kieran and Jhund, Professor Pardeep and Kober, Professor Lars and McMurray, Professor John
Authors: Docherty, K. F., Jhund, P. S., Anand, I., Bengttson, O., Böhm, M., de Boer, R. A., DeMets, D. L., Desai, A. S., Drozdz, J., Howlett, J., Inzucchi, S. E., Johanson, P., Katova, T., Køber, L., Kosiborod, M. N., Langkilde, A. M., Lindholm, D., Martinez, F. A., Merkely, B., Nicolau, J. C., O'Meara, E., Ponikowski, P., Sjöstrand, M., Tereshchenko, S., Solomon, S. D., Verma, S., 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:04 September 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Circulation 142(17): 1623-1632
Publisher Policy:Reproduced under a Creative Commons licence

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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