Comparison of Therapies for Primary Prevention of Esophageal Variceal Bleeding: A Systematic Review and Network Meta-analysis

Mayank Sharma, Siddharth Singh, Vivek Desai, Vijay Shah, Patrick Sequeira Kamath, Mohammad H Murad, Douglas Simonetto

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10 Citations (Scopus)

Abstract

We performed a systematic review with network meta-analysis (NMA) to compare the efficacy of different approaches in primary prevention of esophageal variceal bleeding and overall survival in patients with cirrhosis with large varices. Thirty-two randomized clinical trials (RCTs) with 3,362 adults with cirrhosis with large esophageal varices and no prior history of bleeding, with a minimum of 12 months of follow-up, were included. Nonselective beta-blockers (NSBB), isosorbide-mononitrate (ISMN), carvedilol, and variceal band ligation (VBL), alone or in combination, were compared with each other or placebo. Primary outcomes were reduction of all-cause mortality and prevention of esophageal variceal bleeding. Random-effects NMA was performed and summary estimates were expressed as odds ratio and 95% confidence intervals (OR; CI). Quality of evidence was critically appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. Moderate quality evidence supports NSBB monotherapy (0.70; 0.49-1.00) or in combination with VBL (0.49; 0.23-1.02) or ISMN (0.44; 0.21-0.93) for decreasing mortality in patients with cirrhosis with large esophageal varices and no prior history of bleeding. Moderate-quality evidence supports carvedilol (0.21; 0.08-0.56) and VBL monotherapy (0.33; 0.19-0.55) or in combination with NSBB (0.34; 0.14-0.86), and low-quality evidence supports NSBB monotherapy (0.64; 0.38-1.07) for primary prevention of variceal bleeding. VBL carries a higher risk of serious adverse events compared with NSBB. Conclusion: NSBB monotherapy may decrease all-cause mortality and the risk of first variceal bleeding in patients with cirrhosis with large esophageal varices. Additionally, NSBB carries a lower risk of serious complications compared with VBL. Therefore, NSBB may be the preferred initial approach for primary prophylaxis of esophageal variceal bleeding.

Original languageEnglish (US)
JournalHepatology
DOIs
StatePublished - Jan 1 2019

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Primary Prevention
Hemorrhage
Ligation
isosorbide-5-mononitrate
Esophageal and Gastric Varices
Fibrosis
Therapeutics
Mortality
Varicose Veins
Network Meta-Analysis
Randomized Controlled Trials
Odds Ratio
Placebos
Confidence Intervals
Survival

ASJC Scopus subject areas

  • Hepatology

Cite this

@article{041ebf760abc49f4a7ea649dc1f329e3,
title = "Comparison of Therapies for Primary Prevention of Esophageal Variceal Bleeding: A Systematic Review and Network Meta-analysis",
abstract = "We performed a systematic review with network meta-analysis (NMA) to compare the efficacy of different approaches in primary prevention of esophageal variceal bleeding and overall survival in patients with cirrhosis with large varices. Thirty-two randomized clinical trials (RCTs) with 3,362 adults with cirrhosis with large esophageal varices and no prior history of bleeding, with a minimum of 12 months of follow-up, were included. Nonselective beta-blockers (NSBB), isosorbide-mononitrate (ISMN), carvedilol, and variceal band ligation (VBL), alone or in combination, were compared with each other or placebo. Primary outcomes were reduction of all-cause mortality and prevention of esophageal variceal bleeding. Random-effects NMA was performed and summary estimates were expressed as odds ratio and 95{\%} confidence intervals (OR; CI). Quality of evidence was critically appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. Moderate quality evidence supports NSBB monotherapy (0.70; 0.49-1.00) or in combination with VBL (0.49; 0.23-1.02) or ISMN (0.44; 0.21-0.93) for decreasing mortality in patients with cirrhosis with large esophageal varices and no prior history of bleeding. Moderate-quality evidence supports carvedilol (0.21; 0.08-0.56) and VBL monotherapy (0.33; 0.19-0.55) or in combination with NSBB (0.34; 0.14-0.86), and low-quality evidence supports NSBB monotherapy (0.64; 0.38-1.07) for primary prevention of variceal bleeding. VBL carries a higher risk of serious adverse events compared with NSBB. Conclusion: NSBB monotherapy may decrease all-cause mortality and the risk of first variceal bleeding in patients with cirrhosis with large esophageal varices. Additionally, NSBB carries a lower risk of serious complications compared with VBL. Therefore, NSBB may be the preferred initial approach for primary prophylaxis of esophageal variceal bleeding.",
author = "Mayank Sharma and Siddharth Singh and Vivek Desai and Vijay Shah and Kamath, {Patrick Sequeira} and Murad, {Mohammad H} and Douglas Simonetto",
year = "2019",
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language = "English (US)",
journal = "Hepatology",
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T2 - A Systematic Review and Network Meta-analysis

AU - Sharma, Mayank

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AU - Desai, Vivek

AU - Shah, Vijay

AU - Kamath, Patrick Sequeira

AU - Murad, Mohammad H

AU - Simonetto, Douglas

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N2 - We performed a systematic review with network meta-analysis (NMA) to compare the efficacy of different approaches in primary prevention of esophageal variceal bleeding and overall survival in patients with cirrhosis with large varices. Thirty-two randomized clinical trials (RCTs) with 3,362 adults with cirrhosis with large esophageal varices and no prior history of bleeding, with a minimum of 12 months of follow-up, were included. Nonselective beta-blockers (NSBB), isosorbide-mononitrate (ISMN), carvedilol, and variceal band ligation (VBL), alone or in combination, were compared with each other or placebo. Primary outcomes were reduction of all-cause mortality and prevention of esophageal variceal bleeding. Random-effects NMA was performed and summary estimates were expressed as odds ratio and 95% confidence intervals (OR; CI). Quality of evidence was critically appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. Moderate quality evidence supports NSBB monotherapy (0.70; 0.49-1.00) or in combination with VBL (0.49; 0.23-1.02) or ISMN (0.44; 0.21-0.93) for decreasing mortality in patients with cirrhosis with large esophageal varices and no prior history of bleeding. Moderate-quality evidence supports carvedilol (0.21; 0.08-0.56) and VBL monotherapy (0.33; 0.19-0.55) or in combination with NSBB (0.34; 0.14-0.86), and low-quality evidence supports NSBB monotherapy (0.64; 0.38-1.07) for primary prevention of variceal bleeding. VBL carries a higher risk of serious adverse events compared with NSBB. Conclusion: NSBB monotherapy may decrease all-cause mortality and the risk of first variceal bleeding in patients with cirrhosis with large esophageal varices. Additionally, NSBB carries a lower risk of serious complications compared with VBL. Therefore, NSBB may be the preferred initial approach for primary prophylaxis of esophageal variceal bleeding.

AB - We performed a systematic review with network meta-analysis (NMA) to compare the efficacy of different approaches in primary prevention of esophageal variceal bleeding and overall survival in patients with cirrhosis with large varices. Thirty-two randomized clinical trials (RCTs) with 3,362 adults with cirrhosis with large esophageal varices and no prior history of bleeding, with a minimum of 12 months of follow-up, were included. Nonselective beta-blockers (NSBB), isosorbide-mononitrate (ISMN), carvedilol, and variceal band ligation (VBL), alone or in combination, were compared with each other or placebo. Primary outcomes were reduction of all-cause mortality and prevention of esophageal variceal bleeding. Random-effects NMA was performed and summary estimates were expressed as odds ratio and 95% confidence intervals (OR; CI). Quality of evidence was critically appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. Moderate quality evidence supports NSBB monotherapy (0.70; 0.49-1.00) or in combination with VBL (0.49; 0.23-1.02) or ISMN (0.44; 0.21-0.93) for decreasing mortality in patients with cirrhosis with large esophageal varices and no prior history of bleeding. Moderate-quality evidence supports carvedilol (0.21; 0.08-0.56) and VBL monotherapy (0.33; 0.19-0.55) or in combination with NSBB (0.34; 0.14-0.86), and low-quality evidence supports NSBB monotherapy (0.64; 0.38-1.07) for primary prevention of variceal bleeding. VBL carries a higher risk of serious adverse events compared with NSBB. Conclusion: NSBB monotherapy may decrease all-cause mortality and the risk of first variceal bleeding in patients with cirrhosis with large esophageal varices. Additionally, NSBB carries a lower risk of serious complications compared with VBL. Therefore, NSBB may be the preferred initial approach for primary prophylaxis of esophageal variceal bleeding.

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