Carvedilol and nonselective-beta-blockers vs endoscopic ligation for prophylaxis of esophageal variceal hemorrhage in cirrhosis: Systematic review and meta-analysis

Table 1 Characteristics and results of the included studies

Ref.	Country/setting	Study design	Population (n)	Cirrhosis stage	Intervention (carvedilol/other nonselective beta-blocker)	Comparator (EVL)	Follow-up duration	Bleeding	Lower CI	Higher CI	Bleed related mortality	Lower CI	Higher CI	Bleeding (carvedilol, number/total)	Bleeding (EBL, number/total)	Bleeding-related mortality (carvedilol, number/total)	Bleeding-related mortality (EBL, number/total)
Shah et al[19]	Pakistan (3 tertiary centers: Aga Khan University, Dow University, Jinnah Postgrad Medical Centre, Karachi)	Multicenter RCT	168 cirrhotic patients with medium-large varices (82 carvedilol, 86 EVL)	Mostly viral cirrhosis (approximately 90%); hepatitis C virus most common (approximately 73% carvedilol, 76% EVL); Child-Pugh mean 7.3 (B/C in approximately 55%); ascites approximately 40%	Carvedilol 6.25 mg daily, increase to 12.5 mg/day after 1 week, maintained	EVL sessions every 3 weeks until variceal eradication, then 6-monthly surveillance	Mean follow-up 13.3 ± 12.1 months (range 1-50)	1.61 (HR)	0.27	9.69	1.53	0.71	3.3	7/82	6/86	4/82	4/86
Lay et al[20]	Taiwan (China Medical University Hospital, Taichung Veterans Gen Hospital, Taipei Veterans Gen Hospital)	Prospective RCT	100 cirrhotic patients with high-risk esophageal varices (50 EVL, 50 propranolol)	Mostly viral hepatitis (approximately 72%-74%), 20%-22% alcoholic, others 6%; Child-Pugh A: Approximately 45%, Child-Pugh B: Approximately 40%, Child-Pugh C: Approximately 15%	Propranolol titrated from 40 mg twice daily, mean 68 mg/day; dose adjusted to 20%-25% HR reduction	EVL (weekly × 3, then every 2-3 weeks until eradication; approximately 3.2 sessions, approximately 9.8 bands)	Mean follow-up approximately 35 months	0.89 (odds ratio)	0.36	2.18	1.23	0.5	3.04	11/50	12/50	5/50	4/50
Reiberger et al[17]	Austria (Vienna Hepatic Hemodynamic Lab + Hietzing Hospital)	Prospective cohort with HVPG-guided treatment	104 cirrhotic patients with hepatic venous pressure gradient > 12 mmHg and varices	Alcoholic 55%, viral 33%, metabolic dysfunction-associated steatohepatitis 10%; Child-Pugh A/B/C: 66/30/8	Carvedilol 6.25-50 mg/day (median 12.5 mg), titrated by blood pressure/heart rate, used in propranolol non-responders; 38 patients	EVL (29 patients) every 2-4 weeks until eradication; surveillance every 6 months	mean 19.5 ± 9.7 months (up to 2 years)							3/38	7/29	1/38	5/29
Tripathi et al[18]	UK (5 centers: Edinburgh, Glasgow, Paisley, Birmingham)	Multicenter RCT	152 cirrhotic patients with grade II + esophageal varices (77 carvedilol, 75 VBL)	Alcoholic liver disease 73%; median age 54 years; median Child-Pugh 8 (A/B/C: Approximately 38%/25%/37%); ascites approximately 50%	Carvedilol 6.25 mg/day increase to 12.5 mg if tolerated	Variceal band ligation every 2 weeks until eradication, then surveillance	Median follow-up 20 months (range up to 50 months)	0.41 (HR)	0.19	0.96	1.98	0.59	6.59	8/77	18/75	2/77	2/75
Tripathi et al[21]	United Kingdom, 52 sites	Multicentre, randomized, controlled, open-label trial	265 cirrhotic patients with medium-large esophageal varices (133 carvedilol, 132 VBL)	mean age 59.6 years; 68.3% male; median Child-Pugh 5 (A: Approximately 79%, B: Approximately 21%); model for end-stage liver disease 8; alcohol-related disease 46.4%; 24% with decompensation at baseline	Carvedilol 12.5 mg once daily	Variceal band ligation as per British Society of Gastroenterology guidelines	12 months (median follow-up 1 year)	0.58 (HR)	0.24	1.41				8/133	13/132

CI: Confidence interval; EVL: Endoscopic variceal ligation; HR: Hazard ratio; RCT: Randomized controlled trial; VBL: Variceal band ligation; EBL: Endoscopic band ligation.