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. 2021 Apr 6;4(4):CD013121.
doi: 10.1002/14651858.CD013121.pub2.

Primary prevention of variceal bleeding in people with oesophageal varices due to liver cirrhosis: a network meta-analysis

Davide Roccarina  1 , Lawrence Mj Best  2   3 , Suzanne C Freeman  4 , Danielle Roberts  2 , Nicola J Cooper  4 , Alex J Sutton  4 , Amine Benmassaoud  1 , Maria Corina Plaz Torres  5 , Laura Iogna Prat  1 , Mario Csenar  2 , Sivapatham Arunan  6 , Tanjia Begum  7 , Elisabeth Jane Milne  8 , Maxine Tapp  9 , Chavdar S Pavlov  3 , Brian R Davidson  2 , Emmanuel Tsochatzis  1 , Norman R Williams  10 , Kurinchi Selvan Gurusamy  2   3
Affiliations

Primary prevention of variceal bleeding in people with oesophageal varices due to liver cirrhosis: a network meta-analysis

Davide Roccarina et al. Cochrane Database Syst Rev. .

Abstract

Background: Approximately 40% to 95% of people with cirrhosis have oesophageal varices. About 15% to 20% of oesophageal varices bleed in about one to three years. There are several different treatments to prevent bleeding, including: beta-blockers, endoscopic sclerotherapy, and variceal band ligation. However, there is uncertainty surrounding their individual and relative benefits and harms.

Objectives: To compare the benefits and harms of different treatments for prevention of first variceal bleeding from oesophageal varices in adults with liver cirrhosis through a network meta-analysis and to generate rankings of the different treatments for prevention of first variceal bleeding from oesophageal varices according to their safety and efficacy.

Search methods: We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers to December 2019 to identify randomised clinical trials in people with cirrhosis and oesophageal varices with no history of bleeding.

Selection criteria: We included only randomised clinical trials (irrespective of language, blinding, or status) in adults with cirrhosis and oesophageal varices with no history of bleeding. We excluded randomised clinical trials in which participants had previous bleeding from oesophageal varices and those who had previously undergone liver transplantation or previously received prophylactic treatment for oesophageal varices.

Data collection and analysis: We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the differences in treatments using hazard ratios (HR), odds ratios (OR), and rate ratios with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute for Health and Care Excellence Decision Support Unit guidance. We performed the direct comparisons from randomised clinical trials using the same codes and the same technical details.

Main results: We included 66 randomised clinical trials (6653 participants) in the review. Sixty trials (6212 participants) provided data for one or more comparisons in the review. The trials that provided the information included people with cirrhosis due to varied aetiologies and those at high risk of bleeding from oesophageal varices. The follow-up in the trials that reported outcomes ranged from 6 months to 60 months. All but one of the trials were at high risk of bias. The interventions compared included beta-blockers, no active intervention, variceal band ligation, sclerotherapy, beta-blockers plus variceal band ligation, beta-blockers plus nitrates, nitrates, beta-blockers plus sclerotherapy, and portocaval shunt. Overall, 21.2% of participants who received non-selective beta-blockers ('beta-blockers') - the reference treatment (chosen because this was the most common treatment compared in the trials) - died during 8-month to 60-month follow-up. Based on low-certainty evidence, beta-blockers, variceal band ligation, sclerotherapy, and beta-blockers plus nitrates all had lower mortality versus no active intervention (beta-blockers: HR 0.49, 95% CrI 0.36 to 0.67; direct comparison HR: 0.59, 95% CrI 0.42 to 0.83; 10 trials, 1200 participants; variceal band ligation: HR 0.51, 95% CrI 0.35 to 0.74; direct comparison HR 0.49, 95% CrI 0.12 to 2.14; 3 trials, 355 participants; sclerotherapy: HR 0.66, 95% CrI 0.51 to 0.85; direct comparison HR 0.61, 95% CrI 0.41 to 0.90; 18 trials, 1666 participants; beta-blockers plus nitrates: HR 0.41, 95% CrI 0.20 to 0.85; no direct comparison). No trials reported health-related quality of life. Based on low-certainty evidence, variceal band ligation had a higher number of serious adverse events (number of events) than beta-blockers (rate ratio 10.49, 95% CrI 2.83 to 60.64; 1 trial, 168 participants). Based on low-certainty evidence, beta-blockers plus nitrates had a higher number of 'any adverse events (number of participants)' than beta-blockers alone (OR 3.41, 95% CrI 1.11 to 11.28; 1 trial, 57 participants). Based on low-certainty evidence, adverse events (number of events) were higher in sclerotherapy than in beta-blockers (rate ratio 2.49, 95% CrI 1.53 to 4.22; direct comparison rate ratio 2.47, 95% CrI 1.27 to 5.06; 2 trials, 90 participants), and in beta-blockers plus variceal band ligation than in beta-blockers (direct comparison rate ratio 1.72, 95% CrI 1.08 to 2.76; 1 trial, 140 participants). Based on low-certainty evidence, any variceal bleed was lower in beta-blockers plus variceal band ligation than in beta-blockers (direct comparison HR 0.21, 95% CrI 0.04 to 0.71; 1 trial, 173 participants). Based on low-certainty evidence, any variceal bleed was higher in nitrates than beta-blockers (direct comparison HR 6.40, 95% CrI 1.58 to 47.42; 1 trial, 52 participants). The evidence indicates considerable uncertainty about the effect of the interventions in the remaining comparisons.

Authors' conclusions: Based on low-certainty evidence, beta-blockers, variceal band ligation, sclerotherapy, and beta-blockers plus nitrates may decrease mortality compared to no intervention in people with high-risk oesophageal varices in people with cirrhosis and no previous history of bleeding. Based on low-certainty evidence, variceal band ligation may result in a higher number of serious adverse events than beta-blockers. The evidence indicates considerable uncertainty about the effect of beta-blockers versus variceal band ligation on variceal bleeding. The evidence also indicates considerable uncertainty about the effect of the interventions in most of the remaining comparisons.

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Conflict of interest statement

Davide R: none.

LB: none.

SF: none.

Danielle R: none.

NC: none.

AJS: none.

AB: none.

MPT: none.

LP: none.

MC: none.

SA: none.

TB: none.

EJM: none.

MT: none.

CSP: none.

BRD: none.

ET: none.

NW: none.

KG: none.

Figures

1
1
Study flow diagram. Date of search 17 December 2019. RCT: randomised clinical trial.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
4
4
Network plots: a high resolution version of this image can be found at https://doi.org/10.5281/zenodo.4409371. The network plots showing the outcomes for which network meta‐analysis was performed. The size of the node (circle) provides a measure of the number of trials in which the particular intervention was included as one of the intervention groups. The thickness of the line provides a measure of the number of direct comparisons between two nodes (interventions). BT: balloon tamponade; PC_shunt: portocaval shunt; Sclero: sclerotherapy; Som: somatostatin analogues; TIPS: transjugular intrahepatic portosystemic shunt; Vas: vasopressin analogues; VBL: variceal band ligation.
5
5
Inconsistency factor plots showing the inconsistency factors for the outcomes with direct and indirect evidence available for one or more comparisons. There was no evidence of inconsistency for any of the outcomes where this could be assessed (i.e. the confidence intervals of all the inconsistency factors for all outcomes overlap zero). A higher resolution image of this picture is available at https://doi.org/10.5281/zenodo.4441270. BT: balloon tamponade; PC_shunt: portocaval shunt; Sclero: sclerotherapy; Som: somatostatin analogues; TIPS: transjugular intrahepatic portosystemic shunt; Vas: vasopressin analogues; VBL: variceal band ligation.
6
6
Forest plots showing mortality and the outcomes for which the random‐effects model were different from the fixed‐effect model. The more conservative random‐effects model was used. BBlock: beta‐blockers; Sclero: sclerotherapy; VBL: variceal band ligation.
See this image and copyright information in PMC

Update of

References

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Piscaglia 1998 {published data only}
    1. Piscaglia F, Gaiani S, Siringo S, Gramantieri L, Serra C, Bolondi L. Duplex-Doppler evaluation of the effects of propranolol and isosorbide-5-mononitrate on portal flow and splanchnic arterial circulation in cirrhosis. Alimentary Pharmacology & Therapeutics 1998;12(5):475-81. - PubMed
PROVA study group 1991 {published data only}
    1. Bendtsen F, Henriksen JH, Sorensen TI. Long-term effects of oral propranolol on splanchnic and systemic haemodynamics in patients with cirrhosis and oesophageal varices. Scandinavian Journal of Gastroenterology 1991;26(9):933-9. - PubMed
    1. The PROVA study group. Prophylaxis of first hemorrhage from esophageal varices by sclerotherapy, propranolol or both in cirrhotic patients: a randomized multicenter trial. Hepatology (Baltimore, Md.) 1991;14(6):1016-24. - PubMed
Psilopoulos 2005 {published data only}
    1. Psilopoulos D, Galanis P, Goulas S, Papanikolaou IS, Elefsiniotis I, Liatsos C, et al. Endoscopic variceal ligation vs. propranolol for prevention of first variceal bleeding: a randomized controlled trial. European Journal of Gastroenterology & Hepatology 2005;17(10):1111-7. - PubMed
Quer 1991 {published data only}
    1. Planas R, Boix J, Dominguez M, Abad A, Quer JC, Leon R. Prophylactiv sclerosis of esophageal varices (EV) prospective trial. Journal of Hepatology 1989;9(Suppl 1):S73.
    1. Planas R, Boix J, Dominguez M, Abad LA, Quer JC, Villagrasa M. Prospective randomized trial on prophylactic sclerosis of oesophageal varices: preliminary results. Journal of Hepatology 1990;10(1):P9.
    1. Quer JC, Boix J, Planas R, Domínguez M, Abad-Lacruz A, Humbert P, et al. Prophylactic sclerosis of esophageal varices. Results of a controlled prospective study. Medicina Clinica 1991;96(7):241-4. - PubMed
Rossi 1991 {published data only}
    1. Rossi S, Fornari F, Tansini P, Di Stasi M, Sbolli G, Buscarini E, et al. Prophylactic sclerotherapy of esophageal high bleeding risk varices. A prospective randomized trial, with a long follow-up. Acta Endoscopica 1991;21(3):463-72.
Russo 1989 {published data only}
    1. Russo A, Giannone G, Magnano A, Passanisi G, Longo C. Prophylactic sclerotherapy in nonalcoholic liver cirrhosis: preliminary results of a prospective controlled randomized trial. World Journal of Surgery 1989;13(2):149-53. - PubMed
Santangelo 1988 {published data only}
    1. Santangelo WC, Dueno MI, Estes BL, Krejs GJ. Prophylactic sclerotherapy of large esophageal varices. New England Journal of Medicine 1988;318(13):814-8. - PubMed
Sarin 2013 {published data only}
    1. NCT00772057. Beta-blockers for prevention of growth of small esophageal varices in cirrhosis: a randomized controlled trial (RCT) [Early primary prophylaxis with beta-blockers in prevention of growth of small esophageal varices in cirrhosis: a randomized controlled trial]. clinicaltrials.gov/ct2/show/NCT00772057 (first received 15 October 2008).
    1. Sarin SK, Mishra SR, Sharma P, Sharma BC, Kumar A. Early primary prophylaxis with beta-blockers does not prevent the growth of small esophageal varices in cirrhosis: a randomized controlled trial. Hepatology International 2013;7(1):248-56. - PubMed
Sauerbruch 1988 {published data only}
    1. Sauerbruch T, Wotzka R, Kopcke W, Harlin M, Heldwein W, Bayerdorfer E, et al. Prophylactic sclerotherapy before the first episode of variceal hemorrhage in patients with cirrhosis. New England Journal of Medicine 1988;319(1):8-15. - PubMed
Schepke 2004 {published data only}
    1. Schepke M, Kleber G, Nurnberg D, Willert J, Koch L, Veltzke-Schlieker W, et al. Ligation versus propranolol for the primary prophylaxis of variceal bleeding in cirrhosis. Hepatology (Baltimore, Md.) 2004;40(1):65-72. - PubMed
Seo 2017 {published data only}
    1. Seo YS, Kim MY, Yim HJ, Kim HS, Kim SG, Park SY, et al. Multicenter prospective randomized controlled trial comparing propranolol, endoscopic band ligation, and combination therapy for the primary prophylaxis variceal bleeding in patients with liver cirrhosis. Journal of Hepatology 2017;66(1):S35.
Shah 2014 {published data only}
    1. NCT01070641. RCT of carvedilol versus variceal band ligation in the primary prophylaxis of oesophageal variceal haemorrhage. clinicaltrials.gov/show/NCT01070641 (first received 18 February 2010).
    1. Shah H, Rauf J, Azam Z, Abid S, Hamid S, Jafri W, et al. Randomized controlled trial of carvedilol vs variceal band ligation in the primary prophylaxis of variceal haemorrhage. American Journal of Gastroenterology 2012;107:S148. - PubMed
    1. Shah HA, Azam Z, Rauf J, Abid S, Hamid S, Jafri W, et al. Carvedilol vs. esophageal variceal band ligation in the primary prophylaxis of variceal hemorrhage: a multicentre randomized controlled trial. Journal of Hepatology 2014;60(4):757-64. - PubMed
    1. Shah HA, Rauf J, Azam Z, Abid S, Hamid SS, Jafri SM, et al. Randomized controlled trial of carvedilol vs variceal band ligation in the primary prophylaxis of variceal haemorrhage. Hepatology (Baltimore, Md.) 2012;56:272A. - PubMed
Singh 2012 {published data only}
    1. Singh B, Saxena PD, Rohtagi V, Kumar V. Comparison of endoscopic variceal ligation and propranolol for the primary prevention of variceal bleeding. Journal of the Indian Academy of Clinical Medicine 2012;13(3):214-7.
Snady 1988 {published data only}
    1. Snady H, Feinman L. Prophylactic treatment of esophageal-varices – results of a 5-year randomized trial. Gastrointestinal Endoscopy 1988;34(2):201-2.
Song 1999 {published data only}
    1. Song IH, Kim IH, Choi J, Lyu S, Roe IH. Comparison between the prophylactic endoscopic variceal ligation and propranolol administration for prevention of first bleeding in cirrhotic patients with high-risk esophageal varices: a randomized prospective study. Korean Journal of Gastroenterology 1999;34(2):221-9.
    1. Song IH, Shin JW, Kim IH, Choi J, Lim CY, Kim JW, et al. A prospective randomized trial between the prophylactic endoscopic variceal ligation and propranolol administration for prevention of first bleeding in cirrhotic patients with high-risk esophageal varices. Journal of Hepatology 2000;32:41.
    1. Song IH, Shin JW, Kim IH, Choi J, Lim CY, Kim JW, et al. A prospective randomized trial between the prophylactic endoscopic variceal ligation and propranolol administration for the prevention of first bleeding in cirrhotic patients with high-risk esophageal varices. Journal of Gastroenterology and Hepatology 2000;15(Suppl 1):F1.
Strauss 1999 {published data only}
    1. Strauss E, De Fatima M, Ribeiro GS, Albano A, Honain NZ, Maffei RA Jr, et al. Long-term follow up of a randomized, controlled trial on prophylactic sclerotherapy of small oesophageal varices in liver cirrhosis. Journal of Gastroenterology and Hepatology 1999;14(3):225-30. - PubMed
Svoboda 1999 {published data only}
    1. Svoboda P, Kantorova I, Ochmann J, Kozumplik L, Marsova J. A prospective randomized controlled trial of sclerotherapy vs ligation in the prophylactic treatment of high-risk esophageal varices. Surgical Endoscopy 1999;13(6):580-4. - PubMed
    1. Svoboda P, Kantorova I, Ochmann J, Kozumplik L, Marsova J. Preventive sclerotherapy of esophageal varices with a high risk of hemorrhage: a prospective randomized controlled study. Rozhledy V Chirurgii 1999;78(7):337-42. - PubMed
Thuluvath 2005 {published data only}
    1. Thuluvath PJ, Maheshwari A, Jagannath S, Arepally A. A randomized controlled trial of beta-blockers versus endoscopic band ligation for primary prophylaxis: a large sample size is required to show a difference in bleeding rates. Digestive Diseases and Sciences 2005;50(2):407-10. - PubMed
Tomikawa 2004 {published data only}
    1. Tomikawa M, Shimabukuro R, Okita K, Tsutsumi N, Akahoshi T, Hashizume M, et al. Propranolol alone may not be acceptable to prevent first esophageal variceal bleeding in Japanese cirrhotic patients: randomized controlled trial. Journal of Gastroenterology and Hepatology 2004;19(5):576-81. - PubMed
Tripathi 2009 {published data only}
    1. Leithead JA, Ferguson JW, Tripathi D, Kochar N, Therapondos G, McAvoy NC, et al. Implications of long-term carvedilol administration for portal hypertension-related renal dysfunction: follow-up from a randomised controlled trial. Hepatology (Baltimore, Md.) 2013;58(4 Suppl 1):855a.
    1. Tripathi D, Ferguson JW, Kochar N, Leithead JA, Therapondos G, McAvoy NC, et al. Randomized controlled trial of carvedilol versus variceal band ligation for the prevention of the first variceal bleed. Hepatology (Baltimore, Md.) 2009;50(3):825-33. - PubMed
    1. Tripathi D, Ferguson JW, Kochar N, Leithead JA, Therapondos G, McAvoy NC. Multicenter randomized controlled trial of carvedilol versus variceal band ligation for the prevention of the first variceal bleed. Hepatology (Baltimore, Md.) 2007;46(4 Suppl 1):269a. - PubMed
VA Coop. Variceal Sclerotherapy Group 1991 {published data only}
    1. Gregory P, Hartigan P, Amodeo D, Baum R, Camara D, Colcher H, et al. Prophylactic sclerotherapy for esophageal varices in alcoholic liver-disease – results of a VA cooperative randomized trial. Gastroenterology 1987;92(5):1414.
    1. Veterans Affairs Cooperative Variceal Sclerotherapy Group. Prophylactic sclerotherapy for esophageal varices in men with alcoholic liver disease. Hepatology (Baltimore, Md.) 1991;324(25):1779-84. - PubMed
Wang 2006 {published data only}
    1. Wang HM, Lo GH, Chen WC, Tsai WL, Chan HH, Cheng LC, et al. Comparison of endoscopic variceal ligation and nadolol plus isosorbide-5-mononitrate in the prevention of first variceal bleeding in cirrhotic patients. Journal of the Chinese Medical Association 2006;69(10):453-60. - PubMed
Witzel 1985 {published data only}
    1. Witzel L, Wolbergs E, Merki H. Prophylactic endoscopic sclerotherapy of oesophageal varices. A prospective controlled study. Lancet 1985;1(8432):773-5. - PubMed
Wordehoff 1987 {published data only}
    1. Wordehoff D, Spech HJ, Liehr H. The prophylactic sclerotherapy of oesophageal varices – a prospective, randomised study. Zeitschrift fur Gastroenterologie 1983;21(8):426-7.
    1. Wordehoff D, Spech HJ. Prophylactic sclerosing of esophageal varices. Results of a prospective randomized 7-year longitudinal study. Deutsche Medizinische Wochenschrift 1987;112(24):947-51. - PubMed

References to studies excluded from this review

Abecasis 2003 {published data only}
    1. Abecasis R, Kravetz D, Fassio E, Ameigeiras B, Garcia D, Isla R, et al. Nadolol plus spironolactone in the prophylaxis of first variceal bleed in nonascitic cirrhotic patients: a preliminary study. Hepatology (Baltimore, Md.) 2003;37(2):359-65. - PubMed
Abraczinskas 2001 {published data only}
    1. Abraczinskas DR, Ookubo R, Grace ND, Groszmann RJ, Bosch J, Garcia-Tsao G, et al. Propranolol for the prevention of first esophageal variceal hemorrhage: a lifetime commitment? Hepatology (Baltimore, Md.) 2001;34(6):1096-102. - PubMed
Adson 1984 {published data only}
    1. Adson MA, Heerden JA, Ilstrup DM. The distal splenorenal shunt. Archives of Surgery 1984;119(5):609-14. - PubMed
Agarwala 2011 {published data only}
    1. Agarwala V, Prakash G, Singh R, Paliwal P, Tiwari S, Juber S, et al. Evaluation of treatment with carvedilol in comparison to propranolol in primary/secondary prophylaxis of gastroesophageal variceal bleeding. Indian Journal of Gastroenterology 2011;30(1 Suppl 1):A46.
Albillos 1996 {published data only}
    1. Albillos A, Garcia-Pagan JC, Iborra J, Bandi JC, Cacho G, Paramo MP. Propranolol plus prazosin versus propranolol plus isosorbide 5-mononitrate in the treatment of portal hypertension. Hepatology (Baltimore, Md.) 1996;24(4 Pt 2):206a. - PubMed
Alvarado‐Tapias 2016 {published data only}
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ASGE 1998 {published data only}
    1. American Society for Gastrointestinal Endoscopy. The role of endoscopic therapy in the management of variceal hemorrhage. Gastrointestinal Endoscopy 1998;48(6):697-8. - PubMed
Assi 2000 {published data only}
    1. Assi SA, Sanyal A, Schubert ML. Beta-blocker plus nitrate for primary prophylaxis of variceal bleeding. Gastroenterology 2000;119(4):1170-2. - PubMed
Avgerinos 1994 {published data only}
    1. Avgerinos A, Armonis A, Manolakopoilos S, Rekoumis G, Argirakis G, Raptis S. A randomised controlled trial comparing the effect of somatostatin-14 and octreotide on intravascular oesophageal variceal pressure (IOVP) in liver cirrhosis. Gut 1994;35 Suppl 4:A25. - PubMed
    1. Avgerinos A, Armonis A, Rekoumis G, Manalakopoulos S, Argirakis G, Raptis S, et al. The effect of somatostatin and octreotide on intravascular oesophageal variceal pressure in patients with cirrhosis. Journal of Hepatology 1995;22(3):379-80. - PubMed
Avgerinos 2000 {published data only}
    1. Avgerinos A, Armonis A, Manolakopoulos S, Rekoumis G, Argirakis G, Viazis N, et al. Endoscopic sclerotherapy plus propranolol versus propranolol alone in the primary prevention of bleeding in high risk cirrhotic patients with esophageal varices: a prospective multicenter randomized trial. Gastrointestinal Endoscopy 2000;51(6):652-8. - PubMed
Banares 1999 {published data only}
    1. Banares R, Moitinho E, Piqueras B, Casado M, Garcia-Pagan JC, Diego A, et al. Carvedilol, a new nonselective beta-blocker with intrinsic anti-alpha1-adrenergic activity, has a greater portal hypotensive effect than propranolol in patients with cirrhosis. Hepatology (Baltimore, Md.) 1999;30(1):79-83. - PubMed
Bandi 1998 {published data only}
    1. Bandi JC, Garcia-Pagan JC, Escorsell A, Francois E, Moitinho E, Rodes J, et al. Effects of propranolol on the hepatic hemodynamic response to physical exercise in patients with cirrhosis. Hepatology (Baltimore, Md.) 1998;28(3):677-82. - PubMed
Barrioz 1998 {published data only}
    1. Barrioz T, Borderie C, Ingrand P, Strock P, Silvain C, Beauchant M, et al. Octreotide infusion increases the lower esophageal sphincter tone in cirrhotic patients: a potential role on variceal blood flow. Hepatology (Baltimore, Md.) 1996;24(4 Pt 2):207a.
    1. Barrioz T, Borderie C, Strock P, Ingrand P, Fort E, Silvain C, et al. Effects of octreotide on lower esophageal sphincter in patients with cirrhosis and portal hypertension. Digestive Diseases and Sciences 1998;43(7):1566-71. - PubMed
Batenburg 1990 {published data only}
    1. Batenburg P, Blankenstein M, Boogaard JW, Buuren HR, Hattum J, Hop WC, et al. Prevention of esophageal variceal bleeding. An interim analysis of a controlled multicentre trial. Netherlands Journal of Medicine 1990;37:A31.
Bellis 2003 {published data only}
    1. Bellis L, Berzigotti A, Abraldes JG, Moitinho E, García-Pagán JC, Bosch J, et al. Low doses of isosorbide mononitrate attenuate the postprandial increase in portal pressure in patients with cirrhosis. Hepatology (Baltimore, Md.) 2003;37(2):378-84. - PubMed
Berardi 1974 {published data only}
    1. Berardi RS. Vascular complications of superior mesenteric artery infusion with pitressin in treatment of bleeding esophageal varices. American Journal of Surgery 1974;127(6):757-61. - PubMed
Bhardwaj 2014 {published data only}
    1. Bhardwaj A, Kumar A, Rangegowda D, Kedarisetty CK, Kumar M, Vashishtha C, et al. A prospective, open labeled, randomized controlled trial comparing carvedilol plus VSL#3 versus EVL for primary prophylaxis of esophageal variceal bleeding in cirrhotic patients non-responder to carvedilol. Hepatology (Baltimore, Md.) 2014;60:278A.
Bhardwaj 2019 {published data only}
    1. Bhardwaj A, Jindal A, Sharma MK, Kumar G, Sarin SK. Carvedilol for pre-primary prophylaxis of esophageal varices in cirrhosis – a randomized controlled trial. Hepatology (Baltimore, Md.) 2019;70:488A-9A.
    1. NCT01212250. Carvedilol for pre-primary prophylaxis of esophageal varices in cirrhosis [A prospective, double-blind, randomized placebo-controlled trial of carvedilol for pre-primary prophylaxis of esophageal varices in cirrhosis]. clinicaltrials.gov/show/NCT01212250 (first received 30 September 2010).
Bolognesi 1994 {published data only}
    1. Bolognesi M, Sacerdoti D, Merkel C, Gatta A. Duplex Doppler sonographic evaluation of splanchnic and renal effects of single agent and combined therapy with nadolol and isosorbide-5-mononitrate in cirrhotic patients. Journal of Ultrasound in Medicine 1994;13(12):945-52. - PubMed
Bolognesi 1995 {published data only}
    1. Bolognesi M, Sacerdoti D, Merkel C, Caregaro L, Bellon S, Gatta A. Duplex Doppler ultrasonography allows a multiorgan noninvasive approach to splanchnic pharmacodynamics in patients with cirrhosis. Bildgebung 1995;62(2):138-43. - PubMed
Bolondi 2006 {published data only}
    1. Bolondi L, Gatta A, Salerno F, Bernardi M, Ascione A, Ferrau O, et al. Potassium kanreonate decreases the incidence of portal hypertension-related complications in compensated cirrhosis. A double-blind randomized study. Hepatology (Baltimore, Md.) 2004;40(4 Suppl 1):224a.
    1. Bolondi L, Piscaglia F, Gatta A, Salerno F, Bernardi M, Ascione A, et al. Effect of potassium canrenoate, an anti-aldosterone agent, on incidence of ascites and variceal progression in cirrhosis. Clinical Gastroenterology and Hepatology 2006;4(11):1395-402. - PubMed
Bonilha 2010 {published data only}
    1. Bonilha D, Correia LM, Gomes GF, Brito JD, Costa PP, Lenz L, et al. Endoscopic variceal ligation (EVL) alone versus endoscopic variceal ligation plus propranolol in variceal bleeding prophylaxis in cirrhotic patients. Gastrointestinal Endoscopy 2010;71(5):AB171-2.
Bosch 2005 {published data only}
    1. Bosch J. Is treatment with nadolol effective against the growth of small esophageal varices in patients with cirrhosis? Nature Clinical Practice Gastroenterology and Hepatology 2005;2(1):18-9. - PubMed
Braga 1991 {published data only}
    1. Braga M, Ravelli P, Missale G, Lancini GP, Cestari R. Portal hypertensive patients: effect of oral administration of propranolol on intravascular oesophageal variceal pressure (IOVP). A single-blind random study. Giornale Italiano di Endoscopia Digestiva 1991;14(4):331-40.
Burroughs 1992 {published data only}
    1. Burroughs AK. Should neither sclerotherapy nor propranolol be used prophylactically for oesophageal varices? HPB Surgery 1992;6(2):134-7. - PMC - PubMed
Cales 1990b {published data only}
    1. Cales P. Primary prevention of digestive hemorrhages in cirrhotic patients. Annales de Gastroenterologie et d'Hepatologie 1990;26(5):193-200. - PubMed
Cales 1999 {published data only}
    1. Cales P, Oberti F, Payen JL, Naveau S, Guyader D, Blanc P, et al. Lack of effect of propranolol in the prevention of large oesophageal varices in patients with cirrhosis: a randomized trial. European Journal of Gastroenterology & Hepatology 1999;11(7):741-5. - PubMed
Callow 1970 {published data only}
    1. Callow AD, Resnick RH, Chalmers TC, Ishihara AM, Garceau AJ, O'Hara ET. Conclusions from a controlled trial of the prophylactic portacaval shunt. Surgery 1970;67(1):97-103. - PubMed
Cestari 1990 {published data only}
    1. Cestari R, Braga M, Missale G, Ravelli P, Burroughs AK. Haemodynamic effect of triglycyl-lysine-vasopressin (Glypressin) on intravascular oesophageal variceal pressure in patients with cirrhosis. A randomized placebo controlled trial. Journal of Hepatology 1990;10(2):205-10. - PubMed
Chandok 2012 {published data only}
    1. Chandok N, Kamath PS, Blei A, Bosch J, Carey W, Grace N, et al. Randomised clinical trial: the safety and efficacy of long-acting octreotide in patients with portal hypertension. Alimentary Pharmacology & Therapeutics 2012;35(8):904-12. - PubMed
Cheng 2001 {published data only}
    1. Cheng YS, Pan S, Lien GS, Suk FM, Wu MS, Chen JN, et al. Adjuvant sclerotherapy after ligation for the treatment of esophageal varices: a prospective, randomized long-term study. Gastrointestinal Endoscopy 2001;53(6):566-71. - PubMed
ChiCTR‐IIR‐15007655 {published data only}
    1. ChiCTR-IIR-15007655. The effect of rubber bands placed at each endoscopic session on esophageal variceal obliteration and recurrence in patients with cirrhosis [The effect of rubber bands placed at each endoscopic session on esophageal variceal obliteration and recurrence in patients with cirrhosis: a prospective randomized double-blinded controlled study]. www.chictr.org.cn/showproj.aspx?proj=12787 (first received 26 December 2015).
ChiCTR‐PRRC‐08000228 {published data only}
    1. ChiCTR-PRRC-08000228. Multicenter clinical trial of transjugular intrahepatic portosystemic shunt creation in the management of cirrhosis and portal hypertension. www.chictr.org.cn/showproj.aspx?proj=9299 (first received 1 October 2008).
ChiCTR‐TRC‐12002148 {published data only}
    1. ChiCTR-TRC-12002148. Randomized control trial of carvedilol versus variceal band ligation for the prevention of variceal bleed in HCC. www.chictr.org.cn/showproj.aspx?proj=7401 (first received 19 April 2012).
Cirera 1995 {published data only}
    1. Cirera I, Feu F, Luca A, Garcia-Pagan JC, Fernandez M, Escorsell A, et al. Effects of bolus injections and continuous infusions of somatostatin and placebo in patients with cirrhosis: a double-blind hemodynamic investigation. Hepatology (Baltimore, Md.) 1995;22(1):106-11. - PubMed
Conn 1986 {published data only}
    1. Conn HO. Vasopressin and nitroglycerin in the treatment of bleeding varices: the bottom line. Hepatology (Baltimore, Md.) 1986;6(3):523-5. - PubMed
Conn 1987 {published data only}
    1. Conn HO. Endoscopic sclerotherapy versus percutaneous transhepatic obliteration of varices: a conceptual approach. Gastroenterology 1987;93(6):1428-31. - PubMed
Conn 1993 {published data only}
    1. Conn HO. Sclerotherapy versus beta blockade: unanticipated anomalies of experimental design. Gastroenterology 1993;105(5):1575-7. - PubMed
Copaci 2012 {published data only}
    1. Copaci I, Micu L, Mindrut E, Voiculescu M. Endoscopic variceal ligation alone versus endoscopic variceal ligation plus carvedilol in variceal bleeding prophylaxis in cirrhotic patients. Journal of Hepatology 2012;56:S261-2.
De 2002 {published data only}
    1. De BK, Das D, Sen S, Biswas PK, Mandal SK, Majumdar D, et al. Acute and 7-day portal pressure response to carvedilol and propranolol in cirrhotics. Journal of Gastroenterology and Hepatology 2002;17(2):183-9. - PubMed
De 2003 {published data only}
    1. De BK, Bandyopadhyay K, Das TK, Das D, Biswas PK, Majumdar D, et al. Portal pressure response to losartan compared with propranolol in patients with cirrhosis. American Journal of Gastroenterology 2003;98(6):1371-6. - PubMed
Deschenes 2000 {published data only}
    1. Deschenes M, Barkun AN. Comparison of endoscopic ligation and propranolol for the primary prevention of variceal bleeding. Gastrointestinal Endoscopy 2000;51(5):630-3. - PubMed
Dong 2018 {published data only}
    1. Dong HD. Esophageal fibrosis formation in cirrhosis patients after eradication of esophageal varices by endoscopic band ligation. Journal of Gastroenterology and Hepatology 2018;33(Suppl 4):154.
Dunk 1988 {published data only}
    1. Dunk AA, Moore J, Symon A, Dickie A, Sinclair TS, Mowat NA, et al. The effects of propranolol on hepatic encephalopathy in patients with cirrhosis and portal hypertension. Alimentary Pharmacology & Therapeutics 1988;2(2):143-51. - PubMed
ElRahim 2018 {published data only}
    1. Abd ElRahim AY, Fouad R, Khairy M, Elsharkawy A, Fathalah W, Khatamish H, et al. Efficacy of carvedilol versus propranolol versus variceal band ligation for primary prevention of variceal bleeding. Hepatology International 2018;12(1):75-82. - PubMed
Escorsell 1996 {published data only}
    1. Escorsell A, Feu F, Bordas JM, Garcia-Pagan JC, Luca A, Bosch J, et al. Effects of isosorbide-5-mononitrate on variceal pressure and systemic and splanchnic haemodynamics in patients with cirrhosis. Journal of Hepatology 1996;24(4):423-9. - PubMed
Escorsell 1997a {published data only}
    1. Escorsell A, Bandi JC, Moitinho E, Feu F, Garcia-Pagan JC, Bosch J, et al. Time profile of the haemodynamic effects of terlipressin in portal hypertension. Journal of Hepatology 1997;26(3):621-7. - PubMed
Escorsell 1997b {published data only}
    1. Escorsell A, Bordas JM, Feu F, Garcia-Pagan JC, Gines A, Bosch J, et al. Endoscopic assessment of variceal volume and wall tension in cirrhotic patients: effects of pharmacological therapy. Gastroenterology 1997;113(5):1640-6. - PubMed
Escorsell 2001 {published data only}
    1. Escorsell A, Bandi JC, Andreu V, Moitinho E, Garcia-Pagan JC, Bosch J, et al. Desensitization to the effects of intravenous octreotide in cirrhotic patients with portal hypertension. Gastroenterology 2001;120(1):161-9. - PubMed
Estevens 1996 {published data only}
    1. Estevens J, Guerreiro H, Belo T, Inacio C, Sousa D, Caldeira P, et al. Octreotide versus placebo in elective sclerotherapy of esophageal varices. Gastroenterology 1996;110(4):A15.
eudract2006‐006393‐14 {published data only}
    1. eudract2006-006393-14. Double-blind, randomised, parallel-group, placebo-controlled, multi-centre phase II clinical study on the efficacy and safety of different doses of udenafil in cirrhotic patients with portal hypertension preceded by an open-label pilot phase – udenafil tablets vs. placebo in portal hypertension. www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:200... (first received 23 October 2007).
eudract2012‐000236‐26 {published data only}
    1. eudract2012-000236-26. An exploratory haemodynamic study in patients with compensated cirrhosis and portal hypertension. www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:201... (first received 6 November 2012).
eudract2012‐002489‐11 {published data only}
    1. eudract2012-002489-11. An investigational study to assess the safety and efficacy of a new investigational drug in subjects with compensated liver cirrhosis secondary to non-alcoholic steatohepatitis (NASH). www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:201... (first received 26 February 2013).
eudract2014‐000102‐35 {published data only}
    1. eudract2014-000102-35. Effect of administration of Rifaximin on the increased portal pressure of patients with liver cirrhosis and esophageal varices already treated with propranolol. www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:201... (first received 19 December 2014).
eudract2014‐002018‐21 {published data only}
    1. eudract2014-002018-21. 5-Metyl-tetrahydrofolate in the treatment of portal hypertension in cirrhotics in pharmacologic prophylaxis of variceal bleeding with beta-blockers: a double-blind randomized controlled trial. www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:201... (first received 10 February 2015).
eudract2014‐002300‐24 {published data only}
    1. eudract2014-002300-24. A trial to investigate whether giving albumin to patients with advanced liver cirrhosis will reverse immune suppression and improve outcome from infection. www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:201... (first received 20 March 2015).
eudract2014‐005523‐27 {published data only}
    1. eudract2014-005523-27. Multicenter prospective randomized trial of the effect of rivaroxaban on survival and development of complications of portal hypertension in patients with cirrhosis. www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:201... (first received 30 July 2015).
eudract2017‐001762‐13 {published data only}
    1. eudract2017-001762-13. A clinical trial where neither the doctor, patient or sponsor know whether a placebo or active medicine is being given to the patient with cirrhosis to see if the medicine is safe in the treatment of that disease and to see how study drug is absorbed, distributed through the body and excreted out of the body. www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:201... (first received 1 August 2018).
Fernandez Perez 2008 {published data only}
    1. Fernandez Perez FJ, Jimenez Saenz M, Garcia Montes JM, Rebollo Bernardez J, Herrerias Gutierrez JM. Splanchnic hemodynamic effects of somatostatin and octreotide in cirrhotic patients. A Doppler ultrasonographic study. Revista Espanola de Enfermedades Digestivas 2008;100(9):552-9. - PubMed
Ferrari 2005 {published data only}
    1. Ferrari AP, Paulo GA, Macedo CM, Araujo I, Della Libera E Jr. Efficacy of absolute alcohol injection compared with band ligation in the eradication of esophageal varices. Arquivos de Gastroenterologia 2005;42(2):72-6. - PubMed
Feu 1991 {published data only}
    1. Feu F, Bordas JM, Garcia-Pagán JC, Bosch J, Rodés J. Double-blind investigation of the effects of propranolol and placebo on the pressure of esophageal varices in patients with portal hypertension. Hepatology (Baltimore, Md.) 1991;13(5):917-22. - PubMed
Feu 1993 {published data only}
    1. Feu F, Bordas JM, Luca A, Garcia-Pagan JC, Escorsell A, Bosch J, et al. Reduction of variceal pressure by propranolol: comparison of the effects on portal pressure and azygos blood flow in patients with cirrhosis. Hepatology (Baltimore, Md.) 1993;18(5):1082-9. - PubMed
Fort 1990 {published data only}
    1. Fort E. Haemodynamic effect of triglycyl-lysine vasopressin (Glypressin) on intravascular oesophageal variceal pressure in patients with cirrhosis. A randomized placebo controlled trial. Gastroenterologie Clinique et Biologique 1990;14(11):898-9. - PubMed
Gallant 1992 {published data only}
    1. Gallant DM, Pena JM. Prophylactic therapy of first-episode bleeding in esophageal varices. Alcoholism: Clinical and Experimental Research 1992;16(1):139. - PubMed
Garcia‐Pagán 1991 {published data only}
    1. García-Pagán JC, Feu F, Bosch J, Rodés J. Propranolol compared with propranolol plus isosorbide-5-mononitrate for portal hypertension in cirrhosis. A randomized controlled study. Annals of Internal Medicine 1991;114(10):869-73. - PubMed
Garcia‐Pagán 1996 {published data only}
    1. Garcia-Pagán JC, Escorsell A, Feu F, Bandi JC, Moitinho E, Casado M, et al. Propranolol plus molsidomine vs propranolol alone in the treatment of portal hypertension in patients with cirrhosis. Journal of Hepatology 1996;24(4):430-5. - PubMed
Garcia‐Pagán 2001 {published data only}
    1. Garcia-Pagán JC, Villanueva C, Vila MC, Albillos A, Genesca J, Ruiz-del-Arbol L, et al. Isosorbide mononitrate in the prevention of first variceal bleed in patients who cannot receive beta-blockers. Gastroenterology 2001;121(4):908-14. - PubMed
Garcia‐Pagán 2003 {published data only}
    1. Garcia-Pagán JC, Morillas R, Banares R, Albillos A, Villanueva C, Vila C, et al. Propranolol plus placebo versus propranolol plus isosorbide-5-mononitrate in the prevention of a first variceal bleed: a double-blind RCT. Hepatology (Baltimore, Md.) 2003;37(6):1260-6. - PubMed
Gawrieh 2005 {published data only}
    1. Gawrieh S, Shaker R. Variceal band ligation versus propranolol for primary prophylaxis of variceal bleeding in cirrhosis. Current Gastroenterology Reports 2005;7(3):175-6. - PubMed
Gheorghe 2006 {published data only}
    1. Gheorghe C, Gheorghe L, Iacob S, Iacob R, Popescu I. Primary prophylaxis of variceal bleeding in cirrhotics awaiting liver transplantation. Hepato-gastroenterology 2006;53(70):552-7. - PubMed
    1. Gheorghe C, Gheorghe L, Vadan R, Hrehoret D, Popescu I. Prophylactic banding ligation of high risk esophageal varices in patients on the waiting list for liver transplantation: an interim report. Journal of Hepatology 202;36(Suppl 1):38.
Gilbert 1991 {published data only}
    1. Gilbert DA, Buelow RG, Chung RS, Cunningham JT, Foutch PG, Laine LA, et al. Technology assessment status evaluation: endoscopic band ligation of varices. Gastrointestinal Endoscopy 1991;37(6):670-2. - PubMed
Gong 1998 {published data only}
    1. Gong XH, Zuge CD. The effect of sandostatin used in small dose in treatment of hemorrhage of esophageal varicose. Journal of Practical Hepatology 1998;3(3):174-5.
Gong 2010 {published data only}
    1. Gong WD, Xue K, Chu YK, Wang Q, Yang W, Quan H, et al. Percutaneous transhepatic embolization of gastroesophageal varices combined with partial splenic embolization for variceal bleeding and hypersplenism: a comparison with surgery. Journal of Interventional Radiology 2010;19(2):105-9.
Gotoh 1999 {published data only}
    1. Gotoh Y, Iwakiri R, Sakata Y, Koyama T, Noda T, Matsunaga C, et al. Evaluation of endoscopic variceal ligation in prophylactic therapy for bleeding of oesophageal varices: a prospective, controlled trial compared with endoscopic injection sclerotherapy. Journal of Gastroenterology and Hepatology 1999;14(3):241-4. - PubMed
Gregory 1991 {published data only}
    1. Gregory PB. Prophylactic sclerotherapy for esophageal varices in men with alcoholic liver disease. A randomized, single-blind, multicenter clinical trial. Annals of Internal Medicine 1991;115(Suppl 3):73. - PubMed
Groszmann 2005 {published data only}
    1. Groszmann RJ, Garcia-Tsao G, Bosch J, Grace ND, Burroughs AK, Planas R, et al. Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis. New England Journal of Medicine 2005;353(21):2254-61. - PubMed
Group Francais de la Prevention Pre‐Primaire 1995 {published data only}
    1. Group Francais de la Prevention Pre-Primaire. Propranolol does not decrease the development of large esophageal varices in patients with cirrhosis. A controlled study. Hepatology (Baltimore, Md.) 1995;22(4 Pt 2):155a.
Gupta 1993 {published data only}
    1. Gupta P, Kar P, Chakrovarty A. Prophylactic sclerotherapy in cirrhotics – preliminary results of a prospective, controlled, randomized trial. Indian Journal of Gastroenterology 1993;12(1):27. - PubMed
Hamza 2012 {published data only}
    1. Hamza I, Mahmoud M, Labib S. The initial experience of safety and efficacy of argon plasma coagulation (APC) in the primary prevention of variceal bleeding. Arab Journal of Gastroenterology 2012;13(3):125-9. - PubMed
Hanno 2016 {published data only}
    1. Hanno AE, El Kheir A, El Wazzan DA, Mohamed MI. Medical versus endoscopic treatment of oesophageal varices in liver cirrhosis. United European Gastroenterology Journal 2016;2(Suppl 1):A307.
Hashizume 1993 {published data only}
    1. Hashizume M, Ohta M, Ueno K, Tanoue K, Kitano S, Sugimachi K. Endoscopic ligation of esophageal varices compared with injection sclerotherapy: a prospective randomized trial. Gastrointestinal Endoscopy 1993;39(2):123-6. - PubMed
Helmy 2015 {published data only}
    1. Helmy H, Zaghla HE, Abdel-Razek W, Abbasy M, Elzohry HA, El-Fert AY, et al. Propranolol for prevention of recurrence of varices after endoscopic eradication. Hepatology (Baltimore, Md.) 2015;62:575a.
Hidaka 2011 {published data only}
    1. Hidaka H, Nakazawa T, Shibuya A, Minamino T, Takada J, Tanaka Y, et al. Effects of 1-year administration of olmesartan on portal pressure and TGF-beta1 in selected patients with cirrhosis: a randomized controlled trial. Journal of Gastroenterology 2011;46(11):1316-23. - PubMed
Hua 2007 {published data only}
    1. Hua YX, Yan ZP, Cheng YD, Qiao DL, Zhou B, Chen SW, et al. Therapeutic effects of percutaneous transhepatic variceal embolization combined with partial splenic embolization for portal hypertension. Journal of Interventional Radiology 2007;16(10):665-8.
Hutteroth 1983 {published data only}
    1. Hutteroth TH, Meyer zum Buschenfelde KH. Beta blocker prevention of hemorrhages from esophageal varices in liver cirrhosis. Deutsche Medizinische Wochenschrift 1983;108(14):549-51. - PubMed
Inokuchi 1990 {published data only}
    1. Inokuchi K, Sugimachi K, Sato T, Sato H, Isono K, Okuda K, et al. Improved survival after prophylactic portal nondecompression surgery for esophageal varices: a randomized clinical trial. Hepatology (Baltimore, Md.) 1990;12(1):1-6. - PubMed
Italian Proj. Prop. Prev. Bleed. 1988 {published data only}
    1. Italian Multicenter Project for Propranolol in Prevention of Bleeding. Propranolol for prophylaxis of bleeding in cirrhotic patients with large varices: a multicenter, randomized clinical trial. Hepatology (Baltimore, Md.) 1988;8(1):1-5. - PubMed
    1. The Italian Multicenter Project for Propranolol in Prevention of Bleeding. Propranolol prevents first gastrointestinal bleeding in non-ascitic cirrhotic patients. Final report of a multicenter randomized trial. Journal of Hepatology 1989;9(1):75-83. - PubMed
Iwakiri 2000 {published data only}
    1. Iwakiri R, Koyama T, Hirano M, Uchida Y, Ishibashi S, Kuwahara A, et al. Endoscopic injection sclerotherapy for esophageal varices prolonged survival of patients with hepatocellular carcinoma complicating liver cirrhosis. Gastrointestinal Endoscopy 2000;51(5):569-72. - PubMed
Iwao 1996 {published data only}
    1. Iwao T, Toyonaga A, Oho K, Shigemori H, Sakai T, Tayama C, et al. Effect of vasopressin on esophageal varices blood flow in patients with cirrhosis: comparisons with the effects on portal vein and superior mesenteric artery blood flow. Journal of Hepatology 1996;25(4):491-7. - PubMed
Jackson 1968 {published data only}
    1. Jackson FC, Perrin EB, Smith AG, Dagradi AE, Nadal HM. A clinical investigation of the portacaval shunt. II. Survival analysis of the prophylactic operation. American Journal of Surgery 1968;115(1):22-42. - PubMed
Kainth 2017 {published data only}
    1. Kainth S, Kumar M, Choudhury AK, Anand L, Jindal A, Kumar G, et al. Efficacy and safety of carvedilol in patients of acute-on-chronic liver failure with small or no esophageal varices – a placebo control open label randomised trial. Hepatology (Baltimore, Md.) 2017;66(Suppl 1):83A.
Kalambokis 2005 {published data only}
    1. Kalambokis G, Economou M, Paraskevi K, Konstantinos P, Pappas C, Katsaraki A, et al. Effects of somatostatin, terlipressin and somatostatin plus terlipressin on portal and systemic hemodynamics and renal sodium excretion in patients with cirrhosis. Journal of Gastroenterology and Hepatology 2005;20(7):1075-81. - PubMed
Kanazawa 1988 {published data only}
    1. Kanazawa H, Matsusaka S, Tada N, Miyata K, Tsukui T, Kuroda H, et al. Effect of nadolol on systemic and hepatic hemodynamics, azygos blood flow and esophageal varices in patients with cirrhosis. Prospective, randomized comparison with propranolol. Therapeutic Research 1988;9(6):413-21.
Kim 2016 {published data only}
    1. Kim SG, Kim TY, Sohn JH, Um SH, Seo YS, Baik S K, et al. A randomized, multi-center, open-label study to evaluate the efficacy of carvedilol vs propranolol to reduce portal pressure in patients with liver cirrhosis. American Journal of Gastroenterology 2016;111(11):1582-90. - PubMed
    1. Kim SG, Kim TY, Sohn JH, Um SH, Seo YS, Baik SK, et al. A randomized, multi-center, open-label study to evaluate the long-term effect of carvedilol versus propranolol on reduction in portal pressure in patients with cirrhosis: CARPE study. Hepatology (Baltimore, Md.) 2015;62(1 Suppl):576A.
Kitano 1989 {published data only}
    1. Kitano S, Hashizume M, Yamaga H, Wada H, Iso Y, Iwanaga T, et al. Human thrombin plus 5 per cent ethanolamine oleate injected to sclerose oesophageal varices: a prospective randomized trial. British Journal of Surgery 1989;76(7):715-8. - PubMed
Kitano 1992 {published data only}
    1. Kitano S, Iso Y, Hashizume M, Yamaga H, Koyanagi N, Wada H, et al. Sclerotherapy vs. esophageal transection vs. distal splenorenal shunt for the clinical management of esophageal varices in patients with child class A and B liver function: a prospective randomized trial. Hepatology (Baltimore, Md.) 1992;15(1):63-8. - PubMed
    1. Kitano S, Ohta M, Ueno K, Hashizume M, Iso Y, Koyanagi N, et al. Surgical versus non-surgical treatment in patients with esophageal varices – a prospective randomized study. Nippon Geka Gakkai Zasshi 1992;93(9):1156-8. - PubMed
Kleber 1987 {published data only}
    1. Kleber G, Sauerbruch T, Fischer G, Paumgartner G. Transmural esophageal variceal pressure (increased with somatostatin infusion, not increased with placebo infusion). Zeitschrift Fur Gastroenterologie 1987;25(1):40.
Kleber 1991 {published data only}
    1. Kleber G, Sauerbruch T, Fischer G, Geigenberger G, Paumgartner G. Reduction of transmural oesophageal variceal pressure by metoclopramide. Journal of Hepatology 1991;12(3):362-6. - PubMed
Kobe 1990 {published data only}
    1. Kobe E, Schentke KU. Endoscopic sclerotherapy of esophageal varices – studies of the technic and follow-up. Deutsche Zeitschrift fur Verdauungs- und Stoffwechselkrankheiten 1987;47(4):151-7. - PubMed
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Koch 1994 {published data only}
    1. Koch H, Binmoeller KF, Grimm H, Soehendra N, Henning H, Oehler G. Prophylactic sclerotherapy for esophageal varices: long-term results of a prospective study. Endoscopy 1994;26(9):729-33. - PubMed
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Kong 2013 {published data only}
    1. Kong DR, Ma C, Wang M, Wang JG, Chen C, Zhang L, et al. Effects of propranolol or propranolol plus isosorbide-5-mononitrate on variceal pressure in schistosomiasis. World Journal of Gastroenterology 2013;19(26):4228-33. - PMC - PubMed
Korula 1991 {published data only}
    1. Korula J, Groszmann RJ, Lerner E, Bosch J, Garcia-Tsao G, Grace ND. Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage. Gastroenterology 1991;101(2):590-2. - PubMed
Kuwayama 2005 {published data only}
    1. Kuwayama H, Nishiki R. Randomized controlled trial of long-term proton pump inhibitor (PPI) in the prevention of esophageal variceal bleeding in cirrhotic patients. American Journal of Gastroenterology 2005;100(9):S278.
Lashner 1988 {published data only}
    1. Lashner BA, Hanan IM. Prophylactic sclerotherapy of large esophageal varices. New England Journal of Medicine 1988;319(15):1015-7. - PubMed
Lee 2001 {published data only}
    1. Lee WC, Lin HC, Yang YY, Hou MC, Lee FY, Chang FY, et al. Hemodynamic effects of a combination of prazosin and terlipressin in patients with viral cirrhosis. American Journal of Gastroenterology 2001;96(4):1210-6. - PubMed
Li 1995 {published data only}
    1. Li D, Lu H, Li X, Quan Q, Li X, Lu W. Calcium channel blockers in cirrhotic patients with portal hypertension. Chinese Medical Journal 1995;108(11):803-8. - PubMed
Li 2016a {published data only}
    1. Li B, Chen S, Zhang C, Wei Y. Effects of terlipressin and high-dose octreotide on portal and systemic hemodynamics of cirrhosis patients with gastroesophageal varices: a multicenter randomized controlled trail. Journal of Gastroenterology and Hepatology 2016;31:393.
Lin 1994 {published data only}
    1. Lin HC, Tsai YT, Huang CC, Meng HC, Lee FY, Wang SS, et al. Effects of octreotide on postprandial systemic and hepatic hemodynamics in patients with postnecrotic cirrhosis. Journal of Hepatology 1994;21(3):424-9. - PubMed
Lin 1996a {published data only}
    1. Lin HC, Tsai YT, Yang MC, Lee FY, Hou MC, Chen LS, et al. Effect of octreotide on total effective vascular compliance in patients with posthepatitic cirrhosis. Journal of Hepatology 1996;24(1):81-7. - PubMed
Lin 1996b {published data only}
    1. Lin HC, Tsai YT, Huang YT, Shieh WZ, Hou MC, Lee FY. Hemodynamic effects of a combination of octreotide and terlipressin in patients with cirrhosis. Hepatology (Baltimore, Md.) 1996;24(4 Pt 2):539a.
Lin 2002 {published data only}
    1. Lin HC, Yang YY, Hou MC, Huang YT, Lee WC, Lee FY, et al. Hemodynamic effects of a combination of octreotide and terlipressin in patients with viral hepatitis related cirrhosis. Scandinavian Journal of Gastroenterology 2002;37(4):482-7. - PubMed
Lin 2005 {published data only}
    1. Lin XF, Wu JM, Lin XY, Chen MX, Zhu QH, Wu XL. Effects of isosorbide-5-mononitrate on esophageal manometry of cirrhotic patients with esophageal varices. Chung Hua Kan Tsang Ping Tsa Chih 2005;13(8):611-2. - PubMed
Liu 2004 {published data only}
    1. Liu B, Lin N, Xu RY. Splenectomy combined with endoscopic variceal ligation in treating portal hypertension. Zhong Nan da Xue Xue Bao. Yi Xue Ban [Journal of Central South University. Medical Sciences] 2004;29(1):87-9. - PubMed
Madwar 1998 {published data only}
    1. Madwar MA, El Sayed AM, Salam AA. Prophylactic sclerotherapy versus propranolol therapy for esophageal varices in non-alcoholic liver disease: a controlled randomized study. Hepatology (Baltimore, Md.) 1998;28(4):647A.
Mann 2004 {published data only}
    1. Mann NS. Nadolol versus band ligation for prevention of variceal bleeding. Gastrointestinal Endoscopy 2004;60(6):1036-7. - PubMed
Mastai 1986 {published data only}
    1. Mastai R, Grande L, Bosch J, Bruix J, Rigau J, Kravetz D, et al. Effects of metoclopramide and domperidone on azygos venous blood flow in patients with cirrhosis and portal hypertension. Hepatology (Baltimore, Md.) 1986;6(6):1244-7. - PubMed
Masumoto 1998 {published data only}
    1. Masumoto H, Toyonaga A, Oho K, Iwao T, Tanikawa K. Ligation plus low-volume sclerotherapy for high-risk esophageal varices: comparisons with ligation therapy or sclerotherapy alone. Journal of Gastroenterology 1998;33(1):1-5. - PubMed
McCormick 1992 {published data only}
    1. McCormick PA, Biagini MR, Dick R, Greenslade L, Chin J, Cardin F, et al. Octreotide inhibits the meal-induced increases in the portal venous-pressure of cirrhotic patients with portal-hypertension – a double-blind placebo-controlled study. Hepatology (Baltimore, Md.) 1992;16(5):1180-6. - PubMed
McCormick 1993 {published data only}
    1. McCormick PA, Greenslade L, Chin J, Dick R, McIntyre N, Burroughs AK. The effect of the combination of octreotide and metoclopramide on azygos blood-flow in cirrhotic-patients with portal-hypertension. European Journal of Gastroenterology & Hepatology 1993;5(10):839-43.
McKee 1990 {published data only}
    1. McKee R. A study of octreotide in oesophageal varices. Digestion 1990;45(Suppl 1):60-4. - PubMed
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    1. McKee RF. Sandostatin therapy of acute oesophageal variceal bleeding. Digestion 1993;54(Suppl 1):27-9. - PubMed
Mino 1995 {published data only}
    1. Mino G, Jaramillo JL. Ligation or endoscopic sclerotherapy of esophageal varices. Gastroenterologia y Hepatologia 1995;18(7):384-7. - PubMed
Miyoshi 1997 {published data only}
    1. Miyoshi H, Matsumoto A, Oka M, Sugi K, Yoshimura K, Hongou Y, et al. Efficacy of prophylactic sclerotherapy in patients with hepatocellular carcinoma and varices negative for the red color sign. Gastrointestinal Endoscopy 1997;45(6):498-502. - PubMed
    1. Miyoshi H, Matsumoto A, Oka M, Yoshimura K, Sugi K, Nakajima S, et al. Efficacy of prophylactic sclerotherapy in patients with red color sign negative esophageal-varices as a complication in hepatocellular-carcinoma – a prospective randomized controlled study. Gastroenterology 1995;108(4):A307.
Mo 2014 {published data only}
    1. Mo CY, Li SL. Short-term effect of carvedilol vs propranolol in reduction of hepatic venous pressure gradient in patients with cirrhotic portal hypertension. World Chinese Journal of Digestology 2014;22(27):4146-50.
NCT00006398 {published data only}
    1. NCT00006398. Prevention of esophageal varices by beta-adrenergic blockers [Randomized, double-blind study of timolol (a nonselective beta-adrenergic blocker) vs placebo to prevent complications of hepatic portal hypertension in patients with cirrhosis]. clinicaltrials.gov/ct2/show/NCT00006398 (first received 6 October 1993).
NCT00409084 {published data only}
    1. NCT00409084. Beta blockers versus variceal band ligation and beta blockers for primary prophylaxis of variceal bleeding. clinicaltrials.gov/ct2/show/NCT00409084 (first received 8 December 2006).
NCT00493480 {published data only}
    1. NCT00493480. Danish carvedilol study in portal hypertension [Danish carvedilol study in portal hypertension. Carvedilol in the prevention of bleeding in portal hypertension and esophageal varices]. clinicaltrials.gov/ct2/show/NCT00493480 (first received 28 June 2007).
NCT00799851 {published data only}
    1. NCT00799851. A randomized controlled trial comparing band ligation and cyanoacrylate injection for esophageal varices. clinicaltrials.gov/show/NCT00799851 (first received 1 December 2008).
NCT01059396 {published data only}
    1. NCT01059396. Study on B-blockers to prevent decompensation of cirrhosis with HTPortal [Multicenter, randomized, double-blind, placebo-controlled study on the effectiveness of treatment with beta-blockers to prevent decompensation of cirrhosis with portal hypertension]. clinicaltrials.gov/ct2/show/NCT01059396 (first received 29 January 2010).
NCT01188733 {published data only}
    1. NCT01188733. Efficacy of long-acting octreotide (Sandostatin LAR) in reducing portal pressure in patients with cirrhosis [Hepatic hemodynamic responses to long-acting octreotide in patients with cirrhosis hepatic hemodynamic responses to long-acting octreotide in patients with cirrhosis]. clinicaltrials.gov/ct2/show/NCT01188733 (first received 25 August 2010).
NCT01383044 {published data only}
    1. NCT01383044. Banding ligation with carvedilol versus carvedilol for the prevention of first bleeding [Banding ligation with carvedilol vs carvedilol for the prevention of first bleeding in cirrhotics with moderate varices]. clinicaltrials.gov/show/NCT01383044 (first received 28 June 2011).
NCT02646202 {published data only}
    1. NCT02646202. Scleroligation for eradication of gastroesophageal varices [Scleroligation is a safe and effective new technique for eradication of gastroesophageal varices]. clinicaltrials.gov/ct2/show/NCT02646202 (first received 27 December 2017).
NCT02695732 {published data only}
    1. NCT02695732. The effect of carvedilol vs endoscopic therapy in primary prophylaxis of high-risk esophageal gastric variceal bleeding [Primary prophylaxis of high-risk esophageal gastric variceal bleeding comparing carvedilol and endoscopic therapy: a multicenter randomized controlled trial]. clinicaltrials.gov/show/NCT02695732 (first received 1 March 2016).
NCT03583996 {published data only}
    1. NCT03583996. The SHUNT-V study for varices [The HepQuant SHUNT liver diagnostic kit for likelihood of large esophageal varices: the SHUNT-V study]. clinicaltrials.gov/ct2/show/NCT03583996 (first received 12 July 2018).
Nevens 1996a {published data only}
    1. Nevens F, Lijnen P, VanBilloen H, Fevery J. The effect of long-term treatment with spironolactone on variceal pressure in patients with portal hypertension without ascites. Hepatology (Baltimore, Md.) 1996;23(5):1047-52. - PubMed
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    1. Nishikawa Y, Hosokawa Y, Doi T, Endo H, Tanimizu M, Hyodo I, et al. Evaluation of endoscopic injection sclerotherapy with and without simultaneous ligation for the treatment of esophageal varices. Journal of Gastroenterology 1999;34(2):159-62. - PubMed
Oberti 1999 {published data only}
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Ohmoto 2006 {published data only}
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Okano 2003a {published data only}
    1. Okano H, Shiraki K, Inoue H, Kawakita T, Deguchi M, Sugimoto K, et al. Long-term follow-up of patients with liver cirrhosis after endoscopic esophageal varices ligation therapy: comparison with ethanol injection therapy. Hepato-gastroenterology 2003;50(54):2013-6. - PubMed
Okano 2003b {published data only}
    1. Okano H, Shiraki K, Inoue H, Kawakita T, Deguchi M, Sugimoto K, et al. Long-term follow-up of patients with liver cirrhosis after endoscopic ethanol injection sclerotherapy for esophageal varices. Hepato-gastroenterology 2003;50(53):1556-9. - PubMed
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    1. Orloff MJ. A comparative study of emergency transesophageal ligation and nonsurgical treatment of bleeding esophageal varices in unselected patients with cirrhosis. Surgery 1962;52(1):103-16. - PubMed
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    1. Orloff MJ, Chandler JG, Charters AC, Condon JK, Grambort DE, Modafferi TR, et al. Emergency portacaval shunt treatment for bleeding esophageal varices. Prospective study in unselected patients with alcoholic cirrhosis. Archives of Surgery 1974;108(3):293-9. - PubMed
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    1. Pagliaro L, D'Amico G, Pasta L, Filippazzo MG, Manenti F, Dobrilla G, et al. Propranolol for prophylaxis of bleeding in cirrhotic patients with large varices: a multicenter, randomized clinical trial. Hepatology (Baltimore, Md.) 1988;8(1):1-5. - PubMed
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Pfisterer 2018 {published data only}
    1. Pfisterer N, Dexheimer C, Fuchs EM, Bucsics T, Schwabl P, Mandorfer M, et al. Betablockers do not increase efficacy of band ligation in primary prophylaxis but they improve survival in secondary prophylaxis of variceal bleeding. Alimentary Pharmacology & Therapeutics 2018;47(7):966-79. - PubMed
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Pollo‐Flores 2015 {published data only}
    1. Pollo-Flores P, Soldan M, Santos UC, Kunz DG, Mattos DE, da Silva AC, et al. Three months of simvastatin therapy vs. placebo for severe portal hypertension in cirrhosis: a randomized controlled trial. Digestive and Liver Disease 2015;47(11):957-63. - PubMed
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    1. Poynard T, Cales P, Pasta L, Ideo G, Pascal JP, Pagliaro L, et al. Beta-adrenergic-antagonist drugs in the prevention of gastrointestinal bleeding in patients with cirrhosis and esophageal varices. An analysis of data and prognostic factors in 589 patients from four randomized clinical trials. Franco-Italian Multicenter Study Group. New England Journal of Medicine 1991;324(22):1532-8. - PubMed
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Qi 2007 {published data only}
    1. Qi YF, Zhu SH, Liu XY, Liu B, Li RZ, Zhou P, et al. Endoscopic variceal ligation combined with Hassab's procedure in preventing the recurrence of esophageal varices. Zhong Nan da Xue Xue Bao. Yi Xue Ban [Journal of Central South University. Medical Sciences] 2007;32(3):368-72. - PubMed
Ramond 1999 {published data only}
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Reynolds 1991 {published data only}
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    1. Romero G, Kravetz D, Argonz J, Bildozola M, Suarez A, Terg R. Terlipressin is more effective in decreasing variceal pressure than portal pressure in cirrhotic patients. Journal of Hepatology 2000;32(3):419-25. - PubMed
Rosemurgy 2005 {published data only}
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Santambrogio 1990 {published data only}
    1. Santambrogio R, Bruno S, Opocher E, Galeotti F, Zatta G, Grugni M, et al. Angioscintigraphic assessment of hemodynamic effects of penbutolol in cirrhotics with portal hypertension. A double-blind, randomized, controlled study. Hepato-gastroenterology 1990;37(4):398-402. - PubMed
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Santos 2011 {published data only}
    1. Santos MM, Tolentino LH, Rodrigues RA, Nakao FS, Rohr MR, Paulo GA, et al. Endoscopic treatment of esophageal varices in advanced liver disease patients: band ligation versus cyanoacrylate injection. European Journal of Gastroenterology & Hepatology 2011;23(1):60-5. - PubMed
Sarin 1996 {published data only}
    1. Sarin SK, Guptan RK, Jain AK, Sundaram KR. A randomized controlled trial of endoscopic variceal band ligation for primary prophylaxis of variceal bleeding. European Journal of Gastroenterology & Hepatology 1996;8(4):337-42. - PubMed
Sarin 1999 {published data only}
    1. Sarin SK, Lamba GS, Kumar M, Misra A, Murthy NS. Comparison of endoscopic ligation and propranolol for the primary prevention of variceal bleeding. New England Journal of Medicine 1999;340(13):988-93. - PubMed
Sarin 2005 {published data only}
    1. Sarin SK, Wadhawan M, Agarwal SR, Tyagi P, Sharma BC. Endoscopic variceal ligation plus propranolol versus endoscopic variceal ligation alone in primary prophylaxis of variceal bleeding. American Journal of Gastroenterology 2005;100(4):797-804. - PubMed
Sarin 2010 {published data only}
    1. Sarin SK, Gupta N, Jha SK, Agrawal A, Mishra SR, Sharma BC, et al. Equal efficacy of endoscopic variceal ligation and propranolol in preventing variceal bleeding in patients with noncirrhotic portal hypertension. Gastroenterology 2010;139(4):1238-45. - PubMed
Schepke 2001 {published data only}
    1. Schepke M, Werner E, Biecker E, Schiedermaier P, Heller J, Neef M, et al. Hemodynamic effects of the angiotensin II receptor antagonist irbesartan in patients with cirrhosis and portal hypertension. Gastroenterology 2001;121(2):389-95. - PubMed
Schiedermaier 2002 {published data only}
    1. Schiedermaier P, Harrison P, Arthur M, Grandt D, Sutton R, Drewe J, et al. Effect of the somatostatin analogue lanreotide on meal-stimulated portal blood flow in patients with liver cirrhosis. Digestion 2002;65(1):56-60. - PubMed
Schiedermaier 2003 {published data only}
    1. Schiedermaier P, Koch L, Stoffel-Wagner B, Layer G, Sauerbruch T. Effect of propranolol and depot lanreotide SR on postprandial and circadian portal haemodynamics in cirrhosis. Alimentary Pharmacology & Therapeutics 2003;18(8):777-84. - PubMed
Sen 2002 {published data only}
    1. Sen S, De BK, Biswas PK, Biswas J, Das D, Maity AK. Hemodynamic effect of spironolactone in liver cirrhosis and propranolol-resistant portal hypertension. Indian Journal of Gastroenterology 2002;21(4):145-8. - PubMed
Shang 2010 {published data only}
    1. Shang ZH, Chen HY, Dong HL. Application of timolol in preventing variceal hemorrhage in patients with portal hypertension. Chung-Kuo i Hsueh Ko Hsueh Yuan Hsueh 2010;32(5):553-6. - PubMed
Sharara 2003 {published data only}
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Sheikh 2000 {published data only}
    1. Sheikh RA, Trudeau WL. Evaluation of endoscopic variceal ligation in prophylactic therapy for bleeding of oesophageal varices: a prospective, controlled trial compared with endoscopic injection sclerotherapy. Gastrointestinal Endoscopy 2000;51(2):245-7. - PubMed
Silva 2004 {published data only}
    1. Silva PG, Segovia MR, Backhouse EC, Palma M, Marquez S, Iturriaga RH. Effects of acute octreotide infusion on renal function in patients with cirrhosis and portal hypertension. Revista Medica de Chile 2004;132(2):144-50. - PubMed
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    1. Siqueira ES, Rohr MR, Brandt CQ, Ferrari AP. Esophageal-varices – sclerotherapy or banding ligation – a double-blind, prospective, randomized study in schistosomiasis. Gastrointestinal Endoscopy 1995;41(4):358.
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SLCTR/2007/001 {published data only}
    1. SLCTR/2007/001. Trial on the efficacy of propranolol on the progression of varices in patients with cirrhosis [Prospective randomised controlled trial on the efficacy of propranolol on the progression of small varices /no varices in patients with cirrhosis of the liver. Treatment with propranolol versus no treatment]. slctr.lk/trials/slctr-2007-001 (first received 23 February 2007).
Sohn 2013 {published data only}
    1. Sohn JH, Kim TY, Um SH, Seo YS, Baik SK, Kim MY, et al. A randomized, multi-center, phase IV open-label study to evaluate and compare the effect of carvedilol versus propranolol on reduction in portal pressure in patients with cirrhosis: an interim analysis. Hepatology (Baltimore, Md.) 2013;58(4 Suppl 1):990a.
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    1. Sugano S, Suzuki T, Nishio M, Makino H, Okajima T. Chronic splanchnic hemodynamic effects of low-dose transdermal nitroglycerin versus low-dose transdermal nitroglycerin plus spironolactone in patients with cirrhosis. Digestive Diseases and Sciences 1997;42(3):529-35. - PubMed
Sugano 2001 {published data only}
    1. Sugano S, Yamamoto K, Sasao K, Ishii K, Watanabe M, Tanikawa K. Daily variation of azygos and portal blood flow and the effect of propranolol administration once an evening in cirrhotics. Journal of Hepatology 2001;34(1):26-31. - PubMed
Sussman 2003 {published data only}
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Taniai 2002 {published data only}
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    1. Taranto D, Suozzo R, Sio I, Romano M, Caporaso N, Del Vecchio Blanco C, et al. Effect of metoclopramide on transmural oesophageal variceal pressure and portal blood flow in cirrhotic patients. Digestion 1990;47(1):56-60. - PubMed
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    1. Testa R, Rodriguez G, Dagnino F, Grasso A, Gris A, Marenco S, et al. Effects of beta-adrenoceptor antagonists on cerebral blood-flow of cirrhotic-patients with portal-hypertension. Journal of Clinical Pharmacology 1991;31(2):136-9. - PubMed
Thiel 1993 {published data only}
    1. Thiel DH, Dindzans VJ, Schade RR, Rabinovitz M, Gavaler JS. Prophylactic versus emergency sclerotherapy of large esophageal varices prior to liver transplantation. Digestive Diseases and Sciences 1993;38(8):1505-10. - PubMed
Tincani 1993 {published data only}
    1. Tincani E, Cioni G, Cristani A, D'Alimonte P, Vignoli A, Abbati G, et al. Duplex Doppler ultrasonographic comparison of the effects of propranolol and isosorbide-5-mononitrate on portal hemodynamics. Journal of Ultrasound in Medicine 1993;12(9):525-9. - PubMed
Tincani 1995 {published data only}
    1. Tincani E, Cioni G, D'Alimonte P, Cristani A, Turrini F, Romagnoli R, et al. Effects of propranolol compared with clonidine on portal haemodynamics: a double-blind cross-over study using duplex-Doppler ultrasonography. European Journal of Gastroenterology & Hepatology 1995;7(9):893-7. - PubMed
Triantos 2005 {published data only}
    1. Triantos C, Vlachogiannakos J, Armonis A, Saveriadis A, Kougioumtzian A, Leandro G, et al. Primary prophylaxis of variceal bleeding in cirrhotics unable to take beta-blockers: a randomized trial of ligation. Alimentary Pharmacology & Therapeutics 2005;21(12):1435-43. - PubMed
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Umehara 1999 {published data only}
    1. Umehara M, Onda M, Tajiri T, Toba M, Yoshida H, Yamashita K. Sclerotherapy plus ligation versus ligation for the treatment of esophageal varices: a prospective randomized study. Gastrointestinal Endoscopy 1999;50(1):7-12. - PubMed
Vanruiswyk 1992 {published data only}
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Vorobioff 2002 {published data only}
    1. Vorobioff JD, Gamen M, Kravetz D, Picabea E, Villavicencio R, Bordato J, et al. Effects of long-term propranolol and octreotide on postprandial hemodynamics in cirrhosis: a randomized, controlled trial. Gastroenterology 2002;122(4):916-22. - PubMed
Vorobioff 2007 {published data only}
    1. Vorobioff JD, Ferretti SE, Zangroniz P, Gamen M, Picabea E, Bessone FO, et al. Octreotide enhances portal pressure reduction induced by propranolol in cirrhosis: a randomized, controlled trial. American Journal of Gastroenterology 2007;102(10):2206-13. - PubMed
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    1. Yattoo GN, Kumar A. Clinical efficacy of simvastatin plus propranolol versus propranolol in the long term management of portal hypertension: a randomised controlled study. Journal of Clinical and Experimental Hepatology 2013;3(1 Suppl 1):S78.
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    1. Zargar SA, Shah OJ, Wani AH, Javid G, Shah NA, Ajaz S, et al. Shunt surgery versus endoscopic band ligation for the treatment of esophageal variceal bleeding: a prospective randomized trial. Journal of Gastroenterology and Hepatology 2008;23:A73.
Zironi 1996 {published data only}
    1. Zironi G, Rossi C, Siringo S, Galaverni C, Gaiani S, Piscaglia F, et al. Short- and long-term hemodynamic response to octreotide in portal hypertensive patients: a double-blind, controlled study. Liver 1996;16(4):225-34. - PubMed

References to studies awaiting assessment

Buuren 2003 {published data only}
    1. Buuren HR, Rasch MC, Batenburg PL, Bolwerk CJ, Nicolai JJ, Werf SD, et al. Endoscopic sclerotherapy compared with no specific treatment for the primary prevention of bleeding from esophageal varices. A randomized controlled multicentre trial. BMC Gastroenterology 2003;3:22. - PMC - PubMed
eudract2011‐006208‐11 {published data only}
    1. eudract2011-006208-11. A randomized, controlled multicenter clinical trial comparing endoscopic band ligation versus oral carvedilol in the primary prophylaxis of esophageal variceal bleeding in patients with cirrhosis. www.clinicaltrialsregister.eu/ctr-search/search?query=2011-006208-11 (first received 18 April 2012).

References to ongoing studies

ChiCTR‐IPR‐15005816 {published data only}
    1. ChiCTR-IPR-15005816. Multicenter, randomized, comparative, prospective study on efficacy of EVL-EVS sequential therapy in preventing esophageal variceal hemorrhage. www.chictr.org.cn/showprojen.aspx?proj=10245 (first received 13 January 2015).
NCT02066649 {published data only}
    1. NCT02066649. Carvedilol vs band ligation vs combination therapy for primary prophylaxis of variceal bleeding [A phase 3 study of carvedilol vs variceal band ligation vs combination therapy for primary prophylaxis of variceal bleeding]. clinicaltrials.gov/ct2/show/NCT02066649 (first received 19 February 2014).
NCT03736265 {published data only}
    1. NCT03736265. Carvedilol for prevention of esophageal varices progression [Clinical study of carvedilol for the prevention of the progression of esophageal varices in hepatitis B related cirrhotic patients with anti-viral therapy]. clinicaltrials.gov/ct2/show/NCT03736265 (first received 9 November 2018).
NCT03776955 {published data only}
    1. ISRCTN10324656. Betablockers or placebo for primary prophylaxis of oesophageal varices trial. www.isrctn.com/ISRCTN10324656 (first received 2 November 2018).
    1. NCT03776955. Beta-blockers for oesophageal varices [Beta-blockers or placebo for primary prophylaxis of oesophageal varices (BOPPP Trial). A blinded, multi-centre, clinical effectiveness and cost-effectiveness randomised controlled trial]. clinicaltrials.gov/ct2/show/NCT03776955 (first received 17 December 2018).
NCT04074473 {published data only}
    1. NCT04074473. Impact of nonselective beta-blocker on acute kidney injury in cirrhotic patients with esophageal varices. clinicaltrials.gov/ct2/show/NCT04074473 (first received 30 September 2019).
Tripathi 2019 {published data only}
    1. Tripathi D, Hayes PC, Richardson P, Rowe I, Ferguson J, Devine P, et al. Study protocol for a randomised controlled trial of carvedilol versus variceal band ligation in primary prevention of variceal bleeding in liver cirrhosis (CALIBRE trial). BMJ Open Gastroenterology 2019;6:e000290. - PMC - PubMed

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References to other published versions of this review

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