Short-term hemodynamic effects of β-blockers influence survival of patients with decompensated cirrhosis

J Hepatol. 2020 Oct;73(4):829-841. doi: 10.1016/j.jhep.2020.03.048. Epub 2020 Apr 13.

Abstract

Background & aims: Whether the effect of β-blockers on arterial pressure and/or cardiac function may offset the benefit of reducing portal pressure in advanced cirrhosis is controversial. Herein, we aimed to evaluate the systemic and splanchnic hemodynamic effects of β-blockers in decompensated vs. compensated cirrhosis and to investigate the influence of systemic hemodynamic changes on survival times in decompensated cirrhosis.

Methods: Patients with cirrhosis and high-risk esophageal varices, without previous bleeding, were consecutively included and grouped according to the presence or absence of decompensation (ascites with or without overt encephalopathy). Systemic and hepatic hemodynamic measurements were performed before starting β-blockers and again after 1 to 3 months of treatment (short-term).

Results: Four hundred and three patients were included (190 decompensated and 213 compensated). At baseline, decompensated patients had higher portal pressure than compensated patients and were more hyperdynamic, with higher cardiac output (CO) and lower arterial pressure. Under β-blockers, decompensated patients had lower portal pressure decrease (10 ± 18% vs. 15 ± 12%; p <0.05) and had greater reductions in heart rate (p <0.001) and CO (17 ± 15% vs. 10 ± 21%; p <0.01). Among patients with decompensated cirrhosis, those who died had a greater decrease in CO with β-blockers than survivors (21 ± 14% vs. 15 ± 16%; p <0.05) and CO under β-blockers independently predicted death by competing-risk regression analysis, with good diagnostic accuracy (C-index 0.74; 95% CI 0.66-0.83). Death risk was higher in decompensated patients with CO <5 L/min vs. CO ≥5 L/min (subdistribution hazard ratio 0.44; 95% CI 0.25-0.77; p = 0.004).

Conclusions: In patients with high-risk varices treated to prevent first bleeding, the systemic hemodynamic response to β-blockers is greater and the portal pressure decrease is smaller in those with decompensated cirrhosis. The short-term effect of β-blockers on CO might adversely influence survival in decompensated cirrhosis.

Lay summary: β-blockers are often used to reduce the risk of variceal bleeding in patients with cirrhosis. However, it is not known whether the effect of β-blockers on arterial pressure and/or cardiac function may offset the benefit of reducing portal pressure. Herein, we show that in patients with decompensated cirrhosis the potentially detrimental systemic effects of β-blockers are greater than in compensated patients, while the beneficial pressure lowering effects are reduced. The short-term effect of β-blockers on cardiac output may adversely influence survival in patients with decompensated cirrhosis.

Keywords: Beta blockers; Cirrhotic cardiomyopathy; Hyperdynamic circulation; Portal hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Disease Progression
  • Esophageal and Gastric Varices / etiology*
  • Esophageal and Gastric Varices / physiopathology
  • Female
  • Follow-Up Studies
  • Hemodynamics / drug effects*
  • Humans
  • Hypertension, Portal / drug therapy*
  • Hypertension, Portal / etiology
  • Hypertension, Portal / physiopathology
  • Liver / physiopathology*
  • Liver Cirrhosis / complications*
  • Liver Cirrhosis / mortality
  • Liver Cirrhosis / physiopathology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Survival Rate / trends
  • Time Factors

Substances

  • Adrenergic beta-Antagonists