Liver tests and outcomes in heart failure with reduced ejection fraction: findings from DAPA-HF

Adamson, C. et al. (2022) Liver tests and outcomes in heart failure with reduced ejection fraction: findings from DAPA-HF. European Journal of Heart Failure, 24(10), pp. 1856-1868. (doi: 10.1002/ejhf.2649) (PMID:36054568) (PMCID:PMC9805158)

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Aims: Reflecting both increased venous pressure and reduced cardiac output, abnormal liver tests are common in patients with severe heart failure and are associated adverse clinical outcomes. We aimed to investigate the prognostic significance of abnormal liver tests in ambulatory patients with heart failure with reduced ejection fraction (HFrEF), explore any treatment interaction between bilirubin and sodium-glucose cotransporter 2 inhibitors (SGLT2i) and examine change in liver tests with SGLT2i treatment. Methods and Results: We explored these objectives in the Dapagliflozin And Prevention of Adverse outcomes in Heart Failure trial (DAPA-HF), with focus on bilirubin. We calculated the incidence of cardiovascular death or worsening heart failure by bilirubin tertile. Secondary cardiovascular outcomes were examined, along with the change in liver tests at the end-of-study visit. Baseline bilirubin was available in 4720 patients (99.5%). Participants in the highest bilirubin tertile (T3) have more severe HFrEF (lower LVEF, higher NT-proBNP and worse NYHA class), had a greater burden of atrial fibrillation but less diabetes. Higher bilirubin (T3 versus T1) was associated with worse outcomes even after adjustment for other predictive variables, including NT-proBNP and troponin-T: adjusted HR for the primary outcome 1.73 (95% confidence interval [CI] 1.37-2.17, P<0.001); and 1.52 (1.12-2.07; P=0.01) for cardiovascular death. Baseline bilirubin did not modify the benefits of dapagliflozin. During follow up, dapagliflozin had no effect on liver tests. Conclusion: Bilirubin concentration was an independent predictor of worse outcomes but did not modify the benefits of dapagliflozin in HFrEF. Dapagliflozin was not associated with change in liver tests.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Adamson, Dr Carly and Jhund, Professor Pardeep and McMurray, Professor John and Kober, Professor Lars
Authors: Adamson, C., Cowan, L. M., de Boer, R. A., Diez, M., Drożdż, J., Dukát, A., Inzucchi, S. E., Køber, L., Kosiborod, M. N., Ljungman, C. E.A., Martinez, F. A., Ponikowski, P., Sabatine, M. S., Lindholm, D., Bengtsson, O., Boulton, D. W., Greasley, P. J., Langkilde, A. M., Sjöstrand, M., Solomon, S. D., McMurray, J. J.V., and Jhund, P. S.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:European Journal of Heart Failure
ISSN (Online):1879-0844
Published Online:06 August 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in European Journal of Heart Failure 24(10): 1856-1868
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