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Meta-Analysis
. 2012 Aug 15;2012(8):CD004544.
doi: 10.1002/14651858.CD004544.pub2.

Banding ligation versus beta-blockers for primary prevention in oesophageal varices in adults

Lise Lotte Gluud  1 , Aleksander Krag
Affiliations
Meta-Analysis

Banding ligation versus beta-blockers for primary prevention in oesophageal varices in adults

Lise Lotte Gluud et al. Cochrane Database Syst Rev. .

Abstract

Background: Non-selective beta-blockers are used as a first-line treatment for primary prevention in patients with medium- to high-risk oesophageal varices. The effect of non-selective beta-blockers on mortality is debated and many patients experience adverse events. Trials on banding ligation versus non-selective beta-blockers for patients with oesophageal varices and no history of bleeding have reached equivocal results.

Objectives: To compare the benefits and harms of banding ligation versus non-selective beta-blockers as primary prevention in adult patients with endoscopically verified oesophageal varices that have never bled, irrespective of the underlying liver disease (cirrhosis or other cause).

Search methods: In Febuary 2012, electronic searches (the Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded) and manual searches (including scanning of reference lists in relevant articles and conference proceedings) were performed.

Selection criteria: Randomised trials were included irrespective of publication status, blinding, and language.

Data collection and analysis: Review authors independently extracted data. All-cause mortality was the primary outcome. Intention-to-treat random-effects and fixed-effect model meta-analyses were performed. Results were presented as risk ratios (RR) and 95% confidence intervals (CI) with I(2) statistic values as a measure of intertrial heterogeneity. Subgroup, sensitivity, regression, and trial sequential analyses were performed to evaluate the robustness of the overall results, risks of bias, sources of intertrial heterogeneity, and risks of random errors.

Main results: Nineteen randomised trials on banding ligation versus non-selective beta-blockers for primary prevention in oesophageal varices were included. Most trials specified that only patients with large or high-risk oesophageal varices were included. Bias control was unclear in most trials. In total, 176 of 731 (24%) of the patients randomised to banding ligation and 177 of 773 (23%) of patients randomised to non-selective beta-blockers died. The difference was not statistically significant in a random-effects meta-analysis (RR 1.09; 95% CI 0.92 to 1.30; I(2) = 0%). There was no evidence of bias or small study effects in regression analysis (Egger's test P = 0.997). Trial sequential analysis showed that the heterogeneity-adjusted low-bias trial relative risk estimate required an information size of 3211 patients, that none of the interventions showed superiority, and that the limits of futility have not been reached. When all trials were included, banding ligation reduced upper gastrointestinal bleeding and variceal bleeding compared with non-selective beta-blockers (RR 0.69; 95% CI 0.52 to 0.91; I(2) = 19% and RR 0.67; 95% CI 0.46 to 0.98; I(2) = 31% respectively). The beneficial effect of banding ligation on bleeding was not confirmed in subgroup analyses of trials with adequate randomisation or full paper articles. Bleeding-related mortality was not different in the two intervention arms (29/567 (5.1%) versus 37/585 (6.3%); RR 0.85; 95% CI 0.53 to 1.39; I(2) = 0%). Both interventions were associated with adverse events.

Authors' conclusions: This review found a beneficial effect of banding ligation on primary prevention of upper gastrointestinal bleeding in patient with oesophageal varices. The effect on bleeding did not reduce mortality. Additional evidence is needed to determine whether our results reflect that non-selective beta-blockers have other beneficial effects than on bleeding.

PubMed Disclaimer

Conflict of interest statement

None of the authors have financial or other conflicts of interest with regard to the present work.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Banding ligation versus non‐selective beta blockers for primary prevention in patients with oesophageal varices. The outcome is all‐cause mortality. The heterogeneity‐adjusted low‐bias trial relative risk estimate required information size (HALBRIS) is 3211 patients. The calculation is based on 0% heterogeneity; a proportion of people dying in the control group (Pc) of 23%; a relative risk reduction of 18.7% based on the intervention effect in trials with a low risk of bias; an alpha of 5%; and a beta of 20%. The red lines sloping towards a Z value of 1.96 and ‐1.96 are the trial‐sequential alpha spending monitoring boundaries. The red lines originating from the Z line of 0 broadening towards the HALBRIS are the beta spending monitoring boundaries. The blue line is the cumulative Z curve, which does not cross the alpha or beta spending boundaries.
4
4
Banding ligation versus non‐selective beta blockers for primary prevention in patients with oesophageal varices. The outcome is upper gastrointestinal bleeding. The heterogeneity‐adjusted low‐bias trial relative risk estimate required information size (HALBRIS) is 1890 patients. The calculation is based on 13% heterogeneity; a proportion of people with upper gastrointestinal bleeding in the control group (Pc) of 20.4%; a relative risk reduction of 25.9% based on the intervention effect in trials with a low risk of bias; an alpha of 5%; and a beta of 20%. The red lines sloping towards a Z value of 1.96 and ‐1.96 are the trial sequential alpha spending monitoring boundaries. The blue line is the cumulative Z curve, which crosses the conventional boundary after the sixth trial (314 patients) and the alpha spending boundary after the 13th trial (981 patients).
5
5
Banding ligation versus beta blockers for primary prevention in patients with oesophageal varices. The outcome is variceal bleeding. The heterogeneity‐adjusted low‐bias trial relative risk estimate required information size (HALBRIS) is 2125 patients. The calculation is based on 30% heterogeneity; a proportion of people with upper gastrointestinal bleeding in the control group (Pc) of 19.1%; a relative risk reduction of 39.1% based on the intervention effect in trials with low risk of bias; an alpha of 5%; and a beta of 20%. The red lines sloping towards a Z value of 1.96 and ‐1.96 are the trial sequential alpha spending monitoring boundaries. The blue line is the cumulative Z curve, which crosses the conventional boundary after the fifth trial (224 patient), but not the alpha spending monitoring boundaries.
1.1
1.1. Analysis
Comparison 1 Banding ligation versus non‐selective beta‐blockers, Outcome 1 Mortality.
1.2
1.2. Analysis
Comparison 1 Banding ligation versus non‐selective beta‐blockers, Outcome 2 Mortality stratified by selection bias.
1.3
1.3. Analysis
Comparison 1 Banding ligation versus non‐selective beta‐blockers, Outcome 3 Mortality stratified by attrition bias.
1.4
1.4. Analysis
Comparison 1 Banding ligation versus non‐selective beta‐blockers, Outcome 4 Mortality in full‐paper articles and abstracts.
1.5
1.5. Analysis
Comparison 1 Banding ligation versus non‐selective beta‐blockers, Outcome 5 Upper gastrointestinal bleeding.
1.6
1.6. Analysis
Comparison 1 Banding ligation versus non‐selective beta‐blockers, Outcome 6 Upper gastrointestinal bleeding stratified by selection bias.
1.7
1.7. Analysis
Comparison 1 Banding ligation versus non‐selective beta‐blockers, Outcome 7 Upper gastrointestinal bleeding stratified by attrition bias.
1.8
1.8. Analysis
Comparison 1 Banding ligation versus non‐selective beta‐blockers, Outcome 8 Upper gastrointestinal bleeding in full‐paper articles and abstracts.
1.9
1.9. Analysis
Comparison 1 Banding ligation versus non‐selective beta‐blockers, Outcome 9 Variceal bleeding.
1.10
1.10. Analysis
Comparison 1 Banding ligation versus non‐selective beta‐blockers, Outcome 10 Variceal bleeding stratified by selection bias.
1.11
1.11. Analysis
Comparison 1 Banding ligation versus non‐selective beta‐blockers, Outcome 11 Variceal bleeding stratified by attrition bias.
1.12
1.12. Analysis
Comparison 1 Banding ligation versus non‐selective beta‐blockers, Outcome 12 Variceal bleeding in full‐paper articles and abstracts.
1.13
1.13. Analysis
Comparison 1 Banding ligation versus non‐selective beta‐blockers, Outcome 13 Bleeding‐related mortality.
1.14
1.14. Analysis
Comparison 1 Banding ligation versus non‐selective beta‐blockers, Outcome 14 Adverse events.
1.15
1.15. Analysis
Comparison 1 Banding ligation versus non‐selective beta‐blockers, Outcome 15 Adverse events.
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References

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References to other published versions of this review

Gluud 2009
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