Lowering hepatic venous pressure agent carvedilol versus variceal banding ligation for clinical outcomes of cirrhotic portal hypertension

Figures & data

Figure 1 Flow diagram of the selection process of RCTs in the meta-analysis.

Abbreviation: RCTs, randomized controlled trials.

Table 1 Basic information of the included RCTs

Study	Country	Case (T/C)	Sex (M:F)	Age (years)	Etiology	Severity	Other indexes	Follow-up (months)
Tripathi et al (2009)^Citation11	UK	77/75	54:23/55:20	54.2±9.4/54.5±11.1	Alcoholic: 57/54 Others: 20/21	Child grade (A:B:C): 29:18:29/26:19:30 Varices grade III: 6/7 Red signs: 5/2	Creatinine: 84.6±18.3/83.1±27.0 µmol/L Ascites: 49/53 Bilirubin: 65.0±68.4/95±131.0 µmol/L Albumin: 33.0±6.8/32.6±6.8 g/L Prothrombin time: 12.8±3.1/13.1±3.8 seconds	26.2±22.1/25.5±21.9
Copaci et al (2012)^Citation12 (abstract)	Romania	60/60	/	/	/	Child grade (A:B:C): 15:23:22/16:24:20 MELD score: 12±3.4/11.3±2.99	/	10.14±4.62/8.99±4.83
Mahmod et al (2012)^Citation13	Egypt	25/25	/	/	/	Child grade (A:B:C): 9:7:9/9:6:10	Portal vein congestion index: 0.183±0.09/0.176±0.08	12
Leithead et al (2013)^Citation14 (abstract)	UK	56/44	/	/	/		Creatinine: 82 (70–99)/87(74–100) µmol/L Ascites: 14/7 Hyponatremia: 18/22	15.6 (IQR: 6–37.2)
Stanley et al (2014)^Citation15	UK	33/31	22:11/21:10	51.4±10.8/49.6±12.87	Alcoholic: 58 Fatty liver disease: 3 Primary biliary cirrhosis: 2 Drug-induced injury: 1	Child–Pugh score: 9 (7.0–10.5)/9 (8.0–11.0) MELD score: 13 (8.25–18.5)/14 (11.0–16.0)	Ascites: 12/12 Bilirubin: 39 (19.5–63.0)/35 (23.0–82.0) µmol/L Albumin: 27 (22.5–31.5)/27 (24.0–33.0) g/L Prothrombin time: 15 (13.0–19.0)/16 (14.0–17.0) seconds	30.7 (7.9–47.1)/23.5 (10.3–44.8)
Shah et al (2014)^Citation16	Pakistan	82/86	59:23/63:23	48.3±11.3/47.2±13.2	Viral: 74/77 Alcoholic: 0/3 Others: 8/6	Child grade (A:B:C): 37:35:10/37:37:12	Creatinine: 0.9±0.3/1.0±1.0 mg/dL Ascites: 33/32 Bilirubin: 2.2±2.6/1.9±1.8 mg/dL Albumin: 2.9±0.79/2.9±0.80 g/dL	13.2±11.7/13.4±12.4
Kumar et al (2015)^Citation17 (abstract)	India	47/56	/	44.1±8.5	Alcoholic: 61	Child–Pugh score: 8.6±1.7	/	16.4±5.3
Zhong et al (2016)^Citation18	China	46/44	28:18/24:20	50.3±13.2/48.8±19.1	HBV: 27/26 Alcoholic: 11/12 Others: 8/6	Child grade (A:B): 19:27/15:29 Varices grade (I:II:III): 14:24:8/16:23:5	Hypertension: 6/5 Diabetes: 7/5	1
Khan et al (2017)^Citation19	Pakistan	125/125	77:48/77:55	52.06±14.71/54.07±14.27	/	/	/	6
Abd Elrahim et al (2018)^Citation20	Egypt	84/88	66:34/62:38	51.2±11.0/50.6±5.9		Child grade (A:B:C): 25:24:35/18:21:49 Varices grade (II:III): 57:27/51:33	Creatinine: 1.00±0.30/1.03±0.30 g/dL Bilirubin: 3.04±2.13/2.77±1.39 mg/dL Albumin: 2.63±0.53/2.61±0.51 g/dL	12

Notes: Data were presented as case (n), mean±standard difference, or mean (range). / represents not reported in primary article. References 2 and 8 adopted combination therapy of carvedilol and VBL.

Abbreviations: C, control group (variceal band ligation); F, female; HBV, hepatitis B virus; M, male; MELD, model for end-stage liver disease; RCTs, randomized controlled trials; T, treatment group (carvedilol).

Figure 2 Risk of bias summary of the selected RCTs by the Cochrane tool.

Abbreviation: RCTs, randomized controlled trials.

Figure 3 RR (random effects model) of bleeding incidence between carvedilol and VBL in the subgroups of RCTs assessing the preventive efficacy in 6, 12, 18, and 24 months.

Abbreviations: RCTs, randomized control trials; RR, risk ratio; VBL, variceal banding ligation.

Figure 4 RR (random effects model) of bleeding-related mortality between carvedilol and VBL in the subgroups of RCTs assessing the preventive efficacy in 6, 12, 18, and 24 months.

Abbreviations: RCTs, randomized control trials; RR, risk ratio; VBL, variceal banding ligation.

Figure 5 RR (fixed effects model) of overall mortality between carvedilol and VBL in the subgroups of RCTs assessing the preventive efficacy in 6, 12, and 24 months.

Abbreviations: RCTs, randomized control trials; RR, risk ratio; VBL, variceal banding ligation.

Table 2 Other causes of mortality in the included RCTs

Diagnosis	Trials	Heterogeneity		Effect size
		I^2 (%)	P-value	RR (95% CI)	P-value
Infection	1, 5, 6	0	0.47	1.24 (0.50–3.10)	0.64
Decompensated liver disease	1, 5, 6	44	0.17	0.69 (0.40–1.19)	0.18
Respiratory failure	1, 6	35	0.21	0.67 (0.12–3.91)	0.66
Nonvariceal bleeding	1, 5	52	0.15	0.96 (0.22–4.13)	0.96
Cerebrovascular event	1, 5	0	0.55	0.69 (0.14–3.41)	0.65
Cardiovascular event	1, 5, 6	0	0.45	1.70 (0.63–4.55)	0.29
Others	1, 5	0	0.53	0.14 (0.02–1.07)	0.06

Abbreviations: RCTs, randomized controlled trials; RR, risk ratio.

Figure 6 RR (random effects model) of adverse events between carvedilol and VBL in the subgroups of RCTs assessing the minor and intolerable events.

Abbreviations: RCTs, randomized control trials; RR, risk ratio; VBL, variceal banding ligation.

Table 3 Adverse events of the included RCTs comparing carvedilol with VBL

Diagnosis	Trials	Heterogeneity		Effect size
		I^2 (%)	P-value	RR (95% CI)	P-value
Dyspnea	1, 6	27	0.24	34.86 (4.90–248.07)	0.0004
Nausea and vomiting	1, 6	9	0.29	21.52 (2.97–155.92)	0.002
Transient dysphagia	10, 6	48	0.17	0.02 (0.00–0.12)	0.0001
Symptomatic hypotension	1, 6	0	0.97	5.05 (0.60–42.76)	0.14
Bleeding from postbanding ulcer	5, 6	0	0.66	0.20 (0.02–1.63)	0.13
Intolerable of banding	1, 10	0	0.64	0.17 (0.02–1.41)	0.10
Other	1	81	0.02	0.43 (0.13–1.40)	0.16

Abbreviations: RCTs, randomized controlled trials; VBL, variceal banding ligation.

TripathiDFergusonJWKocharNRandomized controlled trial of carvedilol versus variceal band ligation for the prevention of the first variceal bleedHepatology200950382583319610055

 PubMed Web of Science ®Google Scholar

CopaciIMicuLMindrutEVoiculescuM660 Endoscopic variceal ligation alone versus endoscopic variceal ligation plus carvedilol in variceal bleeding prophylaxis in cirrhotic patientsJ Hepatol2012562S261S262

 Web of Science ®Google Scholar

MahmodAEssaSAbdel AalEDawodHEmanAEvaluation of carvedilol in prevention of first attack of variceal hemorrhage in patients with liver cirrhosisAfro-Egypt J Infect Endem Dis2012228791

 Google Scholar

LeitheadJAFergusonJWTripathiDImplications of long-term carvedilol administration for portal hypertension-related renal dysfunction: follow-up from a randomised controlled trialHepatology201358855A

 Web of Science ®Google Scholar

StanleyAJDicksonSHayesPCMulticentre randomised controlled study comparing carvedilol with variceal band ligation in the prevention of variceal rebleedingJ Hepatol20146151014101924953021

 PubMed Web of Science ®Google Scholar

ShahHAAzamZRaufJCarvedilol vs. esophageal variceal band ligation in the primary prophylaxis of variceal hemorrhage: a multicentre randomized controlled trialJ Hepatol201460475776424291366

 PubMed Web of Science ®Google Scholar

KumarPKumarRSaxenaKNSecondary prophylaxis of variceal hemorrhage: a comparative study of band ligation, carvedilol and propranolol plus isosorbide mononitrateIndian J Gastroenterol201534A54

 Google Scholar

ZhongMZhangBXmLSignificance of NSBB in preventing earlier rehaemorrhagia after endoscopic ligation of the patients with esophageal varicesPract Pharm Clin Remed2016191113116

 Google Scholar

KhanMSMajeedAGhauriFComparison of carvedilol and esophageal variceal band ligation for prevention of variceal bleed among cirrhotic patientsAge (Years)20175214.7154.0754.54

 Google Scholar

Abd ElrahimAYFouadRKhairyMEfficacy of carvedilol versus propranolol versus variceal band ligation for primary prevention of variceal bleedingHepatol Int2018121758229185106

 PubMed Web of Science ®Google Scholar