Liver tests and outcomes in heart failure with reduced ejection fraction: findings from DAPA‐HF. (22nd August 2022)

• Record Type: Journal Article
• Authors: Adamson, Carly; Cowan, Lorna M.; de Boer, Rudolf A.; Diez, Mirta; Drożdż, Jarosław; Dukát, Andre; Inzucchi, Silvio E.; Køber, Lars; Kosiborod, Mikhail N.; Ljungman, Charlotta E.A.; Martinez, Felipe A.; Ponikowski, Piotr; Sabatine, Marc S.; Lindholm, Daniel; Bengtsson, Olof; Boulton, David W.; Greasley, Peter J.; Langkilde, Anna Maria; Sjöstrand, Mikaela; Solomon, Scott D.; McMurray, John J.V.; Jhund, Pardeep S.
• Is Part Of: European journal of heart failure. Volume 24:Number 10(2022)
• Page Start: 1856
• Page End: 1868
• Publication Date: 2022-08-22
• Subjects: Heart failure -- Dapagliflozin -- SGLT2 inhibitor -- Hepatic function -- Bilirubin -- Alkaline phosphatase; Heart failure -- Periodicals; Heart Failure -- Periodicals; Insuffisance cardiaque -- Périodiques; Heart failure; Periodicals; 616.129005
• DOI: 10.1002/ejhf.2649
• Languages: English
• ISSNs: 1388-9842

Abstract

ABSTRACT: 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. Abstract : Summary of key findings in analysis of liver tests in DAPA‐HF. Using restricted cubic splines to model risk of the primary outcome by baseline bilirubin level as a continuous variable shows an essentially linear relationship, with higher bilirubin associated with increased risk. Forest plot for each outcome demonstrates the benefit of dapagliflozin is not modified by baseline bilirubin tertile. Bilirubin adds incremental information about risk of the primary outcome after adjustment for known prognostic markers (high‐sensitivity troponin T [hs‐TnT] and N‐terminal pro‐B‐type natriuretic peptide [NT‐proBNP]). CI, confidence interval; HR, hazard ratio.