BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
Department of Cardiology, University Medical Center and University of Groningen, Groningen, The Netherlands.
Eur J Heart Fail. 2022 Oct;24(10):1856-1868. doi: 10.1002/ejhf.2649. Epub 2022 Aug 22.
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.
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.
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.
ClinicalTrials.gov NCT03036124.
异常的肝功能检查在严重心力衰竭患者中很常见，反映了静脉压升高和心输出量降低，与不良临床结局相关。我们旨在研究射血分数降低的心力衰竭（HFrEF）患者中异常肝功能检查的预后意义，探索胆红素与钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂之间的任何治疗相互作用，并检查 SGLT2 抑制剂治疗对肝功能检查的变化。
我们在达格列净和心力衰竭预防（DAPA-HF）试验中探索了这些目标，重点关注胆红素。我们按胆红素三分位计算心血管死亡或心力衰竭恶化的发生率。检查了次要心血管结局，并在研究结束时检查了肝功能检查的变化。4720 名患者（99.5%）有基线胆红素。胆红素最高三分位组（T3）的患者 HFrEF 更严重（左心室射血分数更低，N 末端 B 型利钠肽前体[NT-proBNP]更高，纽约心脏协会[NYHA]心功能分级更差），心房颤动负担更大，但糖尿病更少。即使在调整其他预测变量（包括 NT-proBNP 和肌钙蛋白 T）后，胆红素升高（T3 与 T1 相比）也与更差的结局相关（主要结局的调整后危险比为 1.73[95%置信区间 1.37-2.17]，p<0.001；心血管死亡的 1.52[1.12-2.07]，p=0.01）。基线胆红素并未改变达格列净的获益。随访期间，达格列净对肝功能检查没有影响。
胆红素浓度是预后更差的独立预测因素，但并未改变 HFrEF 患者中达格列净的获益。达格列净与肝功能检查的变化无关。
ClinicalTrials.gov NCT03036124。
