Non-selective beta blocker (NSBB) is the preferred treatment option for primary prophylaxis of high-risk oesophageal varices, and endoscopic band ligation (EBL) is reserved for those intolerant to NSBB. In this meta-analysis, we aim to compare the outcomes of NSBB, EBL and combined therapy for primary prophylaxis of high-risk oesophageal varices.

Methods

Major databases, such as MedLine, Embase and Cochrane Library were searched in October 2024 to identify studies comparing clinical outcomes between combined approaches versus NSBB versus EBL only. Only randomised trials were included. Meta-analysis was performed using the random-effects model, and heterogeneity was assessed by I²% statistics.

Results

Six randomised trials were included, which consisted of 1011 participants (NSBB 302, EBL 300 and 409 combined) (75.27% males), with an average age of 51.06 years. The NSBBs used were propranolol, nadolol and carvedilol, with an average follow-up of 17.54 months. The combined approach significantly reduced the first episode of variceal bleeding compared to NSBB alone (pooled RR 0.39 [95% CI 0.19–0.76], p = 0.009) and EBL alone (RR 0.46, 0.29–0.74; p = 0.002). The pooled rate of bleeding with the combined approach was 9.4% [95% CI 6%–14.3%], with NSBB being 28.2% [95% CI 12.9%–51%] and with EBL being 13.9% [6%–17%]. Pooled ratios for bleeding-related mortality were significantly better with the combined approach when compared to NSBB alone.

Conclusion

Primary prophylaxis of high-grade varices by combined therapy demonstrated a significantly lower risk of variceal bleeding than NSBB or EBL alone. We recommend these findings be incorporated into forthcoming guidelines.

Conflicts of Interest

The authors declare no conflicts of interest.

Open Research

Data Availability Statement

Data supporting the findings of this study are available from the corresponding author upon reasonable request.

Supporting Information

References

1G. D'Amico, L. Pagliaro, and J. Bosch, “The Treatment of Portal Hypertension: A Meta-Analytic Review,” Hepatology 22, no. 1 (1995): 332–354.
10.1002/hep.1840220145
PubMed Web of Science® Google Scholar
2A. Dell'era and J. Bosch, “Review Article: The Relevance of Portal Pressure and Other Risk Factors in Acute Gastro-Oesophageal Variceal Bleeding,” Alimentary Pharmacology & Therapeutics 20, no. Suppl 3 (2004): 8–15, Discussion 16–17.
10.1111/j.1365-2036.2004.02109.x
PubMed Google Scholar
3G. D'Amico, L. Pagliaro, and J. Bosch, “Pharmacological Treatment of Portal Hypertension: An Evidence-Based Approach,” Seminars in Liver Disease 19, no. 4 (1999): 475–505.
10.1055/s-2007-1007133
PubMed Google Scholar
4T. Poynard, P. Calès, L. Pasta, 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,” New England Journal of Medicine 324, no. 22 (1991): 1532–1538.
10.1056/NEJM199105303242202
CAS PubMed Google Scholar
5R. de Franchis and Baveno VI Faculty, “Expanding Consensus in Portal Hypertension: Report of the Baveno VI Consensus Workshop: Stratifying Risk and Individualizing Care for Portal Hypertension,” Journal of Hepatology 63, no. 3 (2015): 743–752, https://doi.org/10.1016/j.jhep.2015.05.022.
10.1016/j.jhep.2015.05.022
PubMed Web of Science® Google Scholar
6C. Merkel, R. Marin, P. Angeli, et al., “A Placebo-Controlled Clinical Trial of Nadolol in the Prophylaxis of Growth of Small Esophageal Varices in Cirrhosis,” Gastroenterology 127, no. 2 (2004): 476–484.
10.1053/j.gastro.2004.05.004
CAS PubMed Web of Science® Google Scholar
7D. V. Garbuzenko and N. O. Arefyev, “Primary Prevention of Bleeding From Esophageal Varices in Patients With Liver Cirrhosis: An Update and Review of the Literature,” Journal of Evidence-Based Medicine 13, no. 4 (2020): 313–324.
10.1111/jebm.12407
PubMed Google Scholar
8V. Pepe, P. Angeli, and M. Di Pascoli, “Combined Pharmacological and Endoscopic Treatment for Worsening Gastroesophageal Varices in Patients With Cirrhosis,” Clinical and Experimental Gastroenterology 15 (2022): 59–65.
10.2147/CEG.S355392
PubMed Google Scholar
9G. H. Lo, H. L. Liang, K. H. Lai, et al., “The Impact of Endoscopic Variceal Ligation on the Pressure of the Portal Venous System,” Journal of Hepatology 24, no. 1 (1996): 74–80.
10.1016/S0168-8278(96)80189-9
CAS PubMed Google Scholar
10M. C. Hou, H. C. Lin, F. Y. Lee, F. Y. Chang, and S. D. Lee, “Recurrence of Esophageal Varices Following Endoscopic Treatment and Its Impact on Rebleeding: Comparison of Sclerotherapy and Ligation,” Journal of Hepatology 32, no. 2 (2000): 202–208.
10.1016/S0168-8278(00)80064-1
CAS PubMed Google Scholar
11G. H. Lo, K. H. Lai, S. D. Lee, Y. T. Tsai, and K. J. Lo, “Does Propranolol Maintain Post-Sclerotherapy Variceal Obliteration? A Prospective Randomized Study,” Journal of Gastroenterology and Hepatology 8, no. 4 (1993): 358–362.
10.1111/j.1440-1746.1993.tb01528.x
CAS PubMed Google Scholar
12G. H. Lo, K. H. Lai, J. S. Cheng, et al., “Endoscopic Variceal Ligation Plus Nadolol and Sucralfate Compared With Ligation Alone for the Prevention of Variceal Rebleeding: A Prospective, Randomized Trial,” Hepatology 32, no. 3 (2000): 461–465, https://doi.org/10.1053/jhep.2000.16236.
10.1053/jhep.2000.16236
CAS PubMed Web of Science® Google Scholar
13M. J. Page, J. E. McKenzie, P. M. Bossuyt, et al., “The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews,” BMJ (Clinical Research Ed.) 372, no. n71 (2021): n71, https://doi.org/10.1136/bmj.n71.
10.1136/bmj.n71
PubMed Google Scholar
14C. Gheorghe, L. Gheorghe, S. Iacob, R. Iacob, and I. Popescu, “Primary Prophylaxis of Variceal Bleeding in Cirrhotics Awaiting Liver Transplantation,” Hepato-Gastroenterology 53, no. 70 (2006): 552–557.
PubMed Google Scholar
15G. H. Lo, W. C. Chen, H. M. Wang, and C. C. Lee, “Controlled Trial of Ligation Plus Nadolol Versus Nadolol Alone for the Prevention of First Variceal Bleeding,” Hepatology 52, no. 1 (2010): 230–237.
10.1002/hep.23617
CAS PubMed Web of Science® Google Scholar
16S. K. Sarin, S. R. Mishra, P. Sharma, B. C. Sharma, and A. Kumar, “Early Primary Prophylaxis With Beta-Blockers Does Not Prevent the Growth of Small Esophageal Varices in Cirrhosis: A Randomized Controlled Trial,” Hepatology International 7, no. 1 (2013): 248–256.
10.1007/s12072-012-9353-8
PubMed Google Scholar
17D. Q. Bonilha, L. Lenz, L. M. Correia, et al., “Propranolol Associated With Endoscopic Band Ligation Reduces Recurrence of Esophageal Varices for Primary Prophylaxis of Variceal Bleeding: A Randomized-Controlled Trial,” European Journal of Gastroenterology & Hepatology 27, no. 1 (2015): 84–90.
10.1097/MEG.0000000000000227
CAS PubMed Google Scholar
18Y. S. Seo, H. J. Yim, S. G. Kim, 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. 춘· 추계 학술대회,” Journal of Hepatology 66, no. 1 (2017): 10–11.
10.1002/hep.29186
Google Scholar
19H. V. Tevethia, A. Pande, R. Vijayaraghavan, G. Kumar, and S. K. Sarin, “Combination of Carvedilol With Variceal Band Ligation in Prevention of First Variceal Bleed in Child-Turcotte-Pugh B and C Cirrhosis With High-Risk Oesophageal Varices: The ‘CAVARLY TRIAL’,” Gut 73, no. 11 (2024): 1844–1853, https://doi.org/10.1136/gutjnl-2023-331181.
10.1136/gutjnl-2023-331181
CAS Google Scholar
20C. Villanueva, V. Sapena, G. H. Lo, et al., “Improving Primary Prophylaxis of Variceal Bleeding by Adapting Therapy to the Clinical Stage of Cirrhosis. A Competing-Risk Meta-Analysis of Individual Participant Data,” Alimentary Pharmacology & Therapeutics 59, no. 3 (2024): 306–332.
10.1111/apt.17824
CAS PubMed Google Scholar

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Volume45, Issue6

June 2025

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NSBBs, EBL or Combined Therapy for High-Risk Varices: Systematic Review and Meta-Analysis

ABSTRACT

Background and Aims

Methods

Results

Conclusion

Conflicts of Interest

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Data Availability Statement

Supporting Information

References

Citing Literature

References

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NSBBs, EBL or Combined Therapy for High-Risk Varices: Systematic Review and Meta-Analysis

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Letter to the Editor Regarding ‘NSBBs, EBL or Combined Therapy for High-Risk Varices: Systematic Review and Meta-Analysis’

Cardiac Geometry in Cirrhosis: Translation to Public Health and Trial Design

ABSTRACT

Background and Aims

Methods

Results

Conclusion

Conflicts of Interest

Open Research

Data Availability Statement

Supporting Information

References

Citing Literature

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