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

Autor: Adamson C; BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK., Cowan LM; BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK., de Boer RA; Department of Cardiology, University Medical Center and University of Groningen, Groningen, The Netherlands., Diez M; Division of Cardiology, Institute Cardiovascular de Buenos Aires, Buenos Aires, Argentina., Drożdż J; Department Cardiology, Medical University of Lodz, Lodz, Poland., Dukát A; Fifth Department of Internal Medicine, Comenius University in Bratislava, Bratislava, Slovakia., Inzucchi SE; Section of Endocrinology, Yale School of Medicine, New Haven, CT, USA., Køber L; Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Kosiborod MN; Saint Luke's Mid America Heart Institute, University of Missouri, Kansas City, MO, USA.; The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia., Ljungman CEA; Institute of Medicine, Department of Molecular and Clinical Medicine/Cardiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Martinez FA; Universidad Nacional de Córdoba, Córdoba, Argentina., Ponikowski P; Center for Heart Diseases, University Hospital, Wroclaw Medical University, Wroclaw, Poland., Sabatine MS; TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA., Lindholm D; Late Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Bengtsson O; Late Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Boulton DW; Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Gaithersburg, MD, USA., Greasley PJ; Early Research and Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Langkilde AM; Late Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Sjöstrand M; Late Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Solomon SD; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA., McMurray JJV; BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK., Jhund PS; BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
Jazyk: angličtina
Zdroj: European journal of heart failure [Eur J Heart Fail] 2022 Oct; Vol. 24 (10), pp. 1856-1868. Date of Electronic Publication: 2022 Aug 22.
DOI: 10.1002/ejhf.2649
Abstrakt: Aims: Reflecting both increased venous pressure and reduced cardiac output, abnormal liver tests are common in patients with severe heart failure and are associated with 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 (SGLT2) inhibitors and examine change in liver tests with SGLT2 inhibitor treatment.
Methods and Results: We explored these objectives in the Dapagliflozin And Prevention of Adverse outcomes in Heart Failure (DAPA-HF) trial, 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 left ventricular ejection fraction, higher N-terminal pro-B-type natriuretic peptide [NT-proBNP] and worse New York Heart Association class), had a greater burden of atrial fibrillation but less diabetes. Higher bilirubin (T3 vs. T1) was associated with worse outcomes even after adjustment for other predictive variables, including NT-proBNP and troponin T (adjusted hazard ratio for the primary outcome 1.73 [95% confidence interval 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.
Clinical Trial Registration: ClinicalTrials.gov NCT03036124.
(© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)
Databáze: MEDLINE
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