Systemic arterial blood pressure determines the therapeutic window of non-selective beta blockers in decompensated cirrhosis

Aliment Pharmacol Ther. 2019 Sep;50(6):696-706. doi: 10.1111/apt.15439. Epub 2019 Aug 2.

Abstract

Background: The safety of non-selective β-blockers in patients with advanced cirrhosis has been questioned in recent years. It was hypothesised that there is a particular therapeutic window. However, the specific limits still need to be determined.

Aim: To evaluate potential limits of the therapeutic window of non-selective β-blocker therapy in patients with cirrhosis and ascites METHODS: The impact of non-selective β-blockers on 28-day transplant-free survival was analysed in a cohort of 624 consecutive patients with decompensated cirrhosis and ascites. Three potential limits were investigated: spontaneous bacterial peritonitis, acute-on-chronic liver failure, mean arterial blood pressure ≤ 82 and < 65 mm Hg.

Results: Treatment with non-selective β-blockers was associated with a higher 28-day transplant-free survival in the overall cohort (hazard ratio: 0.621; P = .035) as well as in patients with acute-on-chronic liver failure (hazard ratio: 0.578; P = .031) and those with spontaneous bacterial peritonitis (hazard ratio: 0.594; P = .073). In contrast, survival benefits were markedly attenuated in patients with a mean arterial blood pressure ≤ 82 mm Hg and completely lost in those with mean arterial blood pressure < 65 mm Hg (P = .536). In spontaneous bacterial peritonitis patients with a mean arterial blood pressure < 65 mm Hg non-selective β-blocker treatment was associated with renal impairment. Of note, among those with a mean arterial blood pressure ≥ 65 mm Hg non-selective β-blocker intake was consistently associated with superior transplant-free survival (hazard ratio: 0.582; P = .029) irrespective of the presence of spontaneous bacterial peritonitis (hazard ratio: 0.435; P = .028) or acute-on-chronic liver failure (hazard ratio: 0.480 P = .034).

Conclusions: Ascites, acute-on-chronic liver failure and spontaneous bacterial peritonitis do not limit the safe use of non-selective β-blockers in patients with cirrhosis. Mean arterial blood pressure might represent a better indicator to determine the therapeutic window of non-selective β-blocker treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-On-Chronic Liver Failure / drug therapy
  • Acute-On-Chronic Liver Failure / physiopathology
  • Adrenergic beta-Antagonists / administration & dosage*
  • Adult
  • Aged
  • Arterial Pressure*
  • Bacterial Infections / drug therapy
  • Bacterial Infections / physiopathology
  • Female
  • Humans
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / physiopathology
  • Male
  • Middle Aged
  • Peritonitis / drug therapy
  • Peritonitis / physiopathology

Substances

  • Adrenergic beta-Antagonists