Rusman RD, Parewangi ML, Akil F, Daud NAS, Bachtiar RR, Kusuma SH, Rifai A, Tahir AS. Carvedilol and nonselective-beta-blockers vs endoscopic ligation for prophylaxis of esophageal variceal hemorrhage in cirrhosis: Systematic review and meta-analysis. World J Hepatol 2026; 18(5): 117049 [DOI: 10.4254/wjh.v18.i5.117049]
Corresponding Author of This Article
Resha Dermawansyah Rusman, MD, Division of Gastroenterology-Hepatology, Department of Internal Medicine, Faculty of Medicine, Hasanuddin University, Jl Perintis Kemerdekaan Km 10, Makassar 90245, Sulawesi Selatan, Indonesia. reshadermawan@unhas.ac.id
Research Domain of This Article
Gastroenterology & Hepatology
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research-article
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World J Hepatol. May 27, 2026; 18(5): 117049 Published online May 27, 2026. doi: 10.4254/wjh.v18.i5.117049
Carvedilol and nonselective-beta-blockers vs endoscopic ligation for prophylaxis of esophageal variceal hemorrhage in cirrhosis: Systematic review and meta-analysis
Resha Dermawansyah Rusman, Muhammad Luthfi Parewangi, Fardah Akil, Nu'man A S Daud, Rini R Bachtiar, Susanto Hendra Kusuma, Amelia Rifai, Akiko Syawalidhany Tahir
Resha Dermawansyah Rusman, Muhammad Luthfi Parewangi, Fardah Akil, Nu'man A S Daud, Rini R Bachtiar, Susanto Hendra Kusuma, Amelia Rifai, Division of Gastroenterology-Hepatology, Department of Internal Medicine, Faculty of Medicine, Hasanuddin University, Makassar 90245, Sulawesi Selatan, Indonesia
Akiko Syawalidhany Tahir, Department of Internal Medicine, Primaya Hertasning Hospital, Makassar 90221, Sulawesi Selatan, Indonesia
Author contributions: Rusman RD conceived and designed the study, developed the search strategy, collected and analyzed the data, and drafted the initial manuscript; Parewangi ML and Akil F supervised the study methodology, provided critical intellectual input, and reviewed the manuscript for important content; Daud NAS and Bachtiar RR contributed to data interpretation, literature screening, and risk of bias assessment; Kusuma SH, Rifai A, and Tahir AS assisted in manuscript editing, statistical interpretation, preparation of the final version, clinical contextualization, interpretation of findings, and critical revision of the manuscript; All authors read and approved the final manuscript and agree to be accountable for all aspects of the work.
AI contribution statement: Claude (Anthropic) was used during manuscript preparation. Grammarly was also used for grammar and spelling checks. AI assistance was limited strictly to language refinement, given that all authors are non-native English speakers. The authors take full responsibility for the integrity, originality, and accuracy of all content in this manuscript. AI tools were used solely as language and editing aids and did not contribute to the scientific substance, data, or conclusions of this work.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Corresponding author: Resha Dermawansyah Rusman, MD, Division of Gastroenterology-Hepatology, Department of Internal Medicine, Faculty of Medicine, Hasanuddin University, Jl Perintis Kemerdekaan Km 10, Makassar 90245, Sulawesi Selatan, Indonesia. reshadermawan@unhas.ac.id
Received: December 1, 2025 Revised: January 1, 2026 Accepted: February 25, 2026 Published online: May 27, 2026 Processing time: 177 Days and 17 Hours
Abstract
BACKGROUND
Variceal hemorrhage remains a major contributor to morbidity and mortality among patients with liver cirrhosis. Although primary prophylaxis is strongly recommended, uncertainty persists regarding the relative efficacy of carvedilol and other nonselective beta-blockers (NSBBs) vs endoscopic variceal ligation (EVL).
AIM
To compare the efficacy of carvedilol and other NSBBs with EVL for the primary prophylaxis of variceal bleeding in patients with cirrhosis.
METHODS
A systematic search of PubMed, Cochrane Library, EMBASE, and ScienceDirect (August 2025) was conducted to identify randomized controlled trials and prospective cohorts comparing carvedilol or other NSBBs with EVL. Data were pooled using a random-effects meta-analysis, and relative risk (RR) was used as the summary measure. The primary outcome was first variceal bleeding, while the secondary outcome was bleeding-related mortality.
RESULTS
Five studies (n = 752) were included, involving 380 patients receiving carvedilol/NSBBs and 372 patients undergoing EVL. Carvedilol significantly reduced the risk of first variceal bleeding compared with EVL (RR = 0.64, 95% confidence interval [CI]: 0.44-0.94; P = 0.02, I2 = 11%). The absolute bleeding rates were 9.7% with carvedilol vs 15.1% with EVL. Bleed-related mortality did not differ significantly (RR = 0.76, 95%CI: 0.37-1.58; P = 0.47, I2 = 4%), although the event numbers were low. Adverse events differed by modality, with carvedilol predominantly associated with systemic intolerance, whereas EVL caused procedure-related complications.
CONCLUSION
Carvedilol and other NSBBs were associated with a lower risk of first variceal bleeding compared with EVL when used as primary prophylaxis in patients with cirrhosis.
Core Tip: This systematic review and meta-analysis demonstrate that carvedilol, a nonselective beta-blocker, is superior to endoscopic variceal ligation for the primary prevention of esophageal variceal bleeding in patients with cirrhosis. Carvedilol significantly decreases the risk of first variceal bleeding compared to endoscopic variceal ligation. It is associated with different adverse event profiles, highlighting its potential as the preferred first-line prophylactic therapy, especially in settings where resources are limited. This evidence supports a paradigm shift in global practice toward greater adoption of nonselective beta-blockers such as carvedilol for primary prophylaxis.
