Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, TX, USA.
Eur J Heart Fail. 2020 Sep;22(9):1662-1671. doi: 10.1002/ejhf.1853. Epub 2020 May 14.
The prevalence of liver function abnormalities is common in patients with heart failure (HF) with reduced ejection fraction (HFrEF). We assessed the impact of liver function on prognosis and the effect of sacubitril/valsartan on measures of liver function in patients with HFrEF.
The PARADIGM-HF trial was a randomized, double-blind, active treatment-controlled trial. We included 8232 HFrEF patients with available measures of liver function, including transaminases, alkaline phosphatase (ALP) and bilirubin; the primary endpoint was a composite of HF hospitalization and cardiovascular (CV) death. At screening, 11.6% of study patients had total bilirubin above the upper limit of normal (20.5 μmol/L) and 9.2% had ALP above the upper limit of normal (123 IU/L). Although ALP and albumin were associated with an increased risk of outcomes, among conventional test of liver function, total bilirubin was the strongest predictor for the primary endpoint [hazard ratio (HR) 1.10; 95% confidence interval (CI) 1.04-1.15; P < 0.001], HF hospitalization (HR 1.14; 95% CI 1.07-1.22; P < 0.001); CV death (HR 1.07; 95% CI 1.00-1.14; P = 0.040), and all-cause death (HR 1.08; 95% CI 1.02-1.14; P = 0.009). All conventional measures of liver function were significantly improved in the sacubitril/valsartan group compared with the enalapril group after randomization (between-group reduction: total bilirubin 2.4%, 95% CI 0.7-4.2%, P = 0.007; aspartate aminotransferase 7.9%, 95% CI 6.7-9.0%, P < 0.001; alanine aminotransferase 7.7%; 95% CI 6.2-9.3%, P < 0.001; ALP 5.4%, 95% CI 4.4-6.4%, P < 0.001).
Total bilirubin was a significant and independent predictor of CV death or HF hospitalization and all-cause mortality in patients with HFrEF enrolled in PARADIGM-HF. Sacubitril/valsartan improved measures of liver function compared with enalapril.
肝功能异常在射血分数降低的心力衰竭（HFrEF）患者中很常见。我们评估了肝功能对预后的影响以及沙库巴曲缬沙坦对 HFrEF 患者肝功能指标的影响。
PARADIGM-HF 试验是一项随机、双盲、阳性药物对照试验。我们纳入了 8232 例 HFrEF 患者，这些患者有肝功能的检测结果，包括转氨酶、碱性磷酸酶（ALP）和胆红素；主要终点是心力衰竭住院和心血管（CV）死亡的复合终点。在筛查时，研究患者中有 11.6%的总胆红素高于正常值上限（20.5μmol/L），9.2%的 ALP 高于正常值上限（123IU/L）。尽管 ALP 和白蛋白与不良结局风险增加相关，但在常规肝功能检测中，总胆红素是预测主要终点的最强指标[风险比（HR）1.10；95%置信区间（CI）1.04-1.15；P<0.001]、心力衰竭住院（HR 1.14；95%CI 1.07-1.22；P<0.001）；CV 死亡（HR 1.07；95%CI 1.00-1.14；P=0.040）和全因死亡（HR 1.08；95%CI 1.02-1.14；P=0.009）。与依那普利组相比，随机分组后沙库巴曲缬沙坦组所有常规肝功能指标均显著改善（组间差值：总胆红素 2.4%，95%CI 0.7-4.2%，P=0.007；天冬氨酸氨基转移酶 7.9%，95%CI 6.7-9.0%，P<0.001；丙氨酸氨基转移酶 7.7%，95%CI 6.2-9.3%，P<0.001；ALP 5.4%，95%CI 4.4-6.4%，P<0.001）。
总胆红素是 PARADIGM-HF 中纳入的射血分数降低心力衰竭患者 CV 死亡或心力衰竭住院和全因死亡率的显著且独立的预测因子。与依那普利相比，沙库巴曲缬沙坦改善了肝功能指标。
