Carvedilol for portal hypertension in cirrhosis: systematic review with meta-analysis

Abstract

ObjectiveTo assess the clinical and haemodynamic effects of carvedilol for patients with cirrhosis and portal hypertension.DesignA systematic review and meta-analysis.Data sourcesWe searched PubMed, Cochrane library databases, EMBASE and the Science Citation Index Expanded through December 2015. Only randomised controlled trials (RCTs) were included.Outcome measureWe calculated clinical outcomes (all-cause mortality, bleeding-related mortality, upper gastrointestinal bleeding) as well as haemodynamic outcomes (hepatic venous pressure (HVPG) reduction, haemodynamic response rate, post-treatment arterial blood pressure (mean arterial pressure; MAP) and adverse events).Results12 RCTs were included. In 7 trials that looked at haemodynamic outcomes compared carvedilol versus propranolol, showing that carvedilol was associated with a greater reduction (%) of HVPG within 6 months (mean difference −8.49, 95% CI −12.36 to −4.63) without a greater reduction in MAP than propranolol. In 3 trials investigating differences in clinical outcomes between carvedilol versus endoscopic variceal band ligation (EVL), no significant differences in mortality or variceal bleeding were demonstrated. 1 trial compared clinical outcomes between carvedilol versus nadolol plus isosorbide-5-mononitrate (ISMN), and showed that no significant difference in mortality or bleeding had been found. 1 trial comparing carvedilol versus nebivolol showed a greater reduction in HVPG after 14 days follow-up in the carvedilol group.ConclusionsCarvedilol may be more effective in decreasing HVPG than propranolol or nebivolol and it may be as effective as EVL or nadolol plus ISMN in preventing variceal bleeding. However, the overall quality of evidence is low. Further large-scale randomised studies are required before we can make firm conclusions.Trial registration numberCRD42015020542.

EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis

“…Carvedilol, an NSBB with intrinsic anti-alpha-1 receptor activity, has been associated with a greater reduction in portal pressure than the traditional NSBBs and has therefore become a valuable alternative. 180 Its beneficial action on alpha-1 receptors reduces both porto-collateral and intrahepatic resistance, however, this is at the cost of more profound effects on systemic arterial pressure, particularly in decompensated patients. The problem with all the recommendations mentioned so far is that they are based on high quality RCTs that usually excluded patients with more advanced cirrhosis, while major controversy has arisen in recent years regarding the use and safety of NSBBs in patients with advanced disease, particularly in those with refractory ascites and/or SBP.…”

Carvedilol use is associated with improved survival in patients with liver cirrhosis and ascites

“…Carvedilol, an NSBB with intrinsic anti-alpha 1 receptor activity, has been associated with a greater reduction in portal pressure than the traditional beta blocker, propranolol [9]. In a meta-analysis, the proportion of patients achieving target haemodynamic response was higher with carvedilol than propranolol [9]. Additionally, the use of carvedilol has been shown to reduce portal pressure in those who initially failed to respond to propranolol.…”

Carvedilol for prevention of variceal bleeding: a systematic review and meta analysis

“…The efficacy of carvedilol has been explored in a previous systematic review [33], but this incorporated a limited number of trials and focused mainly on surrogate outcomes related to variceal bleeding. Compared to this meta-analysis, we identified a beneficial effect of carvedilol against EVL on mortality.…”