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Carvedilol for portal hypertension in cirrhosis: systematic review with meta-analysis
Tong Li1, Wenbo Ke1, Ping Sun1
1Hepatobiliary Surgery Centre, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Insights
Carvedilol shows promise in reducing hepatic venous pressure gradient (HVPG) in cirrhosis patients, potentially outperforming propranolol and nebivolol. However, evidence quality is low, necessitating further research for definitive conclusions on its clinical efficacy.
Area of Science:
- Hepatology
- Cardiology
- Pharmacology
Background:
- Portal hypertension is a serious complication of cirrhosis.
- Effective management strategies are crucial for improving patient outcomes.
- Carvedilol is a beta-blocker with alpha-blocking activity, investigated for its effects in portal hypertension.
Purpose of the Study:
- To systematically review and meta-analyze the clinical and hemodynamic effects of carvedilol in patients with cirrhosis and portal hypertension.
- To compare carvedilol's efficacy against other treatments like propranolol, endoscopic variceal band ligation (EVL), and nadolol plus isosorbide-5-mononitrate (ISMN).
Main Methods:
- Systematic review and meta-analysis of randomized controlled trials (RCTs).
- Searched major databases (PubMed, Cochrane, EMBASE, Science Citation Index Expanded) up to December 2015.
- Assessed clinical outcomes (mortality, bleeding) and hemodynamic outcomes (HVPG, MAP).
Main Results:
- Carvedilol demonstrated a greater reduction in hepatic venous pressure gradient (HVPG) compared to propranolol and nebivolol.
- No significant differences in mortality or variceal bleeding were observed when comparing carvedilol with EVL or nadolol plus ISMN.
- Carvedilol did not show a greater reduction in mean arterial pressure (MAP) than propranolol.
Conclusions:
- Carvedilol may be more effective than propranolol or nebivolol in decreasing HVPG.
- Carvedilol appears to be as effective as EVL or nadolol plus ISMN in preventing variceal bleeding.
- The overall quality of evidence is low, and further large-scale RCTs are needed to confirm these findings.
Objective:
To assess the clinical and haemodynamic effects of carvedilol for patients with cirrhosis and portal hypertension.
Design:
A systematic review and meta-analysis.
Data Sources:
We searched PubMed, Cochrane library databases, EMBASE and the Science Citation Index Expanded through December 2015. Only randomised controlled trials (RCTs) were included.
Outcome Measure:
We 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).
Results:
12 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.
Conclusions:
Carvedilol 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 Number:
CRD42015020542.
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