TABLE 1.

Characteristics of the studies comparing beta-blockers versus placebo

References	Comparison (intervention and time of outcome assessment)	Patient characteristics	Child-Pugh Class (A/B/C)/ Score	NSBB Titration method	Mean NSBB dose (mean±SD; range)	Etiology (%)	Initial number of patients randomized	Number of patients for each comparison	HVPG measurement technique
Lebrec18	Propranolol (p.o.) vs. Placebo 1 month	Within 15 d after variceal hemorrhage (with patient stable)	NR	25% reduction in HR	NR	81% alcohol 19% cryptogenic	16 (8 vs. 8)	8 vs. 8	NR
Lebrec19	Propranolol (p.o.) vs. Placebo 1 h, 1,3,9 mo Only 1 h data included in the present analysis	10–15 d after variceal hemorrhage	NR	25% reduction in HR	158 mg/d	100% alcohol	24 (12 vs. 12)	12 vs. 12 for 1 h comparison	NR
Pomier-Layrargues20	Propranolol vs. placebo 10 d	Patients after variceal hemorrhage, within 24 h of control of the bleeding episode	4/10/5	Started at 40 mg twice daily, and subsequent dosing was titrated to produce plasma propranolol concentrations between 50 and 150 ng per mL	102 mg/daya	74% alcohol 10% viral 16% cryptogenic	19 (11 vs. 8)	11 vs. 8	Balloon catheter
Groszmann21	Propranolol (p.o.) vs. placebo 3,12,24 mo Only data at 3 mo analyzed	Patients with varices without previous bleeding	Mean 8.1 ± 2.1	Increase in dose weekly until one of the following achieved (a) a 25% reduction in HVPG, (b) a decrease in HVPG to 12 mm Hg or less, or (c) a decrease in HR to 55 beats/min or less.	132±78 mg/dayb	78% alcohol 22% nonalcohol-associated	102 (51 vs. 51)	45 vs. 39 at 3 mo	Balloon catheter
Bendtsen22	Propranolol (p.o.) vs. no treatment 12 mo	Patients with varices without previous bleeding	12/9/3	Initial dose 160 mg, adjusted weekly with 80 mg tablets until a decrease in HR of 25% was achieved	NR	88% alcohol-associated 12% nonalcohol-associated	46 (unclear distribution between propranolol vs. placebo)	14 vs. 10	Straight catheter
Bendtsen23	Propranolol (i.v.) vs. no treatment (both groups with a test meal) We report measurements after 2 h, when the meal effect is over	Patients with varices without previous bleeding	3/9/1	0.1 mg/kg propranolol i.v. Followed by a constant infusion of 1 mcg/min/kg	14.2 mg (first 2 h)	100% alcohol	13 (6 vs. 7)	6 vs. 7	Straight catheter
Feu24	Propranolol (i.v. vs. placebo) 20 min Effects on HVPG and on variceal pressure	All varices 43% previous hemorrhage	Mean 6.3 ± 1.6	Propranolol (0.15 mg/kg), intravenously over 10 min	NR	51% alcohol 27% cryptogenic 22% viral	37 (21 vs. 16)	21 vs. 16	Balloon catheter
Luca25	Propranolol (i.v. vs. placebo) 20 min	93% varices 59% previous hemorrhage	Mean 6.9 ± 1.7	Propranolol (0.15 mg/kg), intravenously over 10 min	NR	33% alcohol 58% viral 9% cryptogenic	58 (44 vs. 14) (randomization 3:1)	44 vs. 14	Balloon catheter
Escorsell26	Propranolol (i.v. vs. placebo) 40 min Effects on variceal pressure	All varices 33% previous hemorrhage	Mean 7.8 ± 1.8	Propranolol (0.15 mg/kg), intravenously over 10 min	NR	50% alcohol-associated 50% Nonalcohol-associated	18 (9 vs. 9)	9 vs. 9	NA
Albillos27	Propranolol (i.v. vs. placebo) 30 min	All varices 44% previous hemorrhage	Mean 6.7 ± 1.4	Propranolol (0.15 mg/kg), intravenously over 10 min	12.3 ± 11.5 mg	55% alcohol 45% nonalcohol-associated	80 (60 vs. 20)	60 vs. 20	Balloon catheter
Bandi28	Propranolol (i.v. vs. placebo) 20 min	All varices. 13% previous hemorrhage	Mean 6.1 ± 0.6	0.15 mg · kg-1 over 15 min followed by a constant infusion of 0.2 mg · h-1.	NR	48% alcohol 52% viral	23 (12 vs. 11)	12 vs. 11	Balloon catheter
Bañares29	Carvedilol (p.o.) vs. propranolol (i.v.) vs. placebo after 1 h of administration	All esophageal varices 62% had previous variceal bleed 57% had ascites	13/15/7	Carvedilol (25 mg orally). Propranolol (0.15 mg/kg i.v., followed by a continuous infusion of 0.2 mg/kg)	NA	57% alcohol	35 (14 vs. 14 vs. 7)	35 (14 vs. 14 vs. 7)	Balloon catheter
Merkel30	Nadolol vs placebo	All patients small varices 25% ascites	Mean 6.9 ± 1.8	Starting from 40 mg/day with a target of a 25% decrease or a heart rate of 50 bpm	62±25 mg/day	Alcohol 57% Viral 39% others 4%	161 (83 vs. 78)	10 vs. 9	Balloon catheter
Groszmann31	Timolol vs placebo 12 mo and yearly thereafter up to 8 y 12 mo data used for analysis	All patients compensated without varices	189/24/0 Mean: 5.4 ± 0.7	Started at 5 mg per day and increased by 5 mg every 3 d until either: HR reduced by 25%, HR < 55, or a maximum of 80 mg was reached	Median: 10.8 (range: 1.25–80)  mg/day	Viral 67% Alcohol 24% cryptogenic 5% Others 4%	213 (108 vs. 105)	72 vs. 82	Balloon catheter
Mishra32	BB vs. control vs. cyanoacrylate	Patients with cirrhosis with gastric varices of size > 10 mm who have never bled.	29/35/25	Propranolol started at 20 mg bid, increased by 20 mg to achieve a HR of 55/min, or to a maximum of 360 mg/day if SBP >90 mm Hg	140 (80–240) mg/day	51% alcohol 29% cryptogenic 20% others	89 (30 Cyanoacrylate , 29 BB, 30 no treatment)	89 (30 Cyanoacrylate , 29 BB, 30 no treatment)	Balloon catheter
Sarin33	Propranolol (p.o) vs. placebo 12 mo	Small varices without previous bleeding	Mean 7.5 ± 2.1	Target HR of 55/min or to maximal dose of 360 mg/day	Median dose 120 (range 40–360)	54% viral 35% alcohol 11% Others	150 (77 vs. 73)	25 vs. 24 (random sample of one-third of the total sample)	Balloon catheter
Bhardwaj34	Carvedilol (p.o.) vs. placebo 12 mo	Small varices and no history of bleeding	Mean 6.9 ± 1.8	Start dose of 3.125 mg BID, increased up to a maximum of 12.5 mg BID if SBP > 100 mm Hg and heart rate >55 bpm	12±1.67 mg/day	44% cryptogenic 25% viral 24% alcohol 7% others	140 (70 vs 70)	52 vs 48	Balloon catheter
Villanueva35	Propranolol or carvedilol (according to acute HVPG response) Versus placebo. 67% received propranolol and 33% received carvedilol. HVPG at 12 mo and yearly up to 24 mo Only 12 mo data used for analysis	All patients compensated with HVPG >= 10 mm Hg and no large varices	161/40/0 Mean 5.8 ± 0.9	HVPG acute responders: propranolol 40 mg BID increased up to 160 mg BID. Nonresponders: carvedilol, starting with 6.25 mg/day increased up to 25 mg/day, keeping HR > 55 and SBP> 90 mm Hg	95±78 mg/day	56% viral 16% alcohol 13% others 9% alcohol/viral 6% MASLD	201 (100 vs. 101)	78 vs. 78	Balloon catheter

Note: In those studies in which response is assessed at different time points, the earlier assessment of response time point was used for analysis (the reason is that over time the population is increasingly selected (dropouts and patients with terminal events).

^aMean dose extracted from Villeneuve et al (clinical report of the trial)36

^bMean dose extracted from Conn et al (clinical report of the trial)37

^cMean HVPG/SD at 1 year was extracted from Figure 2B of the manuscript.

Abbreviations: BID, twice daily; MASLD, metabolic-associated steatotic liver disease; NA, not applicable; NR, not reported; NSBB, nonselective beta-blockers ; SBP, systolic blood pressure.