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. 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). 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. Randomised trials were included irrespective of publication status, blinding, and language. 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. 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. 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.[CINAHL Note: The Cochrane Collaboration systematic reviews contain interactive software that allows various calculations in the MetaView.]
AIM: To perform an updated meta-analysis comparing β-blockers (BB) with endoscopic variceal banding ligation (EVBL) in the primary prophylaxis of esophageal variceal bleeding.
MATERIAL AND METHODS: Randomized controlled trials were identified through electronic databases, article reference lists and conference proceedings. Analysis was performed using both fixed-effect and random-effect models. Heterogeneity and publication bias were systematically taken into account. Main outcomes were variceal bleeding rates and all-cause mortality, calculated overall and at 6, 12, 18 and 24 months.
RESULTS: 19 randomized controlled trials were analyzed including a total of 1,483 patients. Overall bleeding rates were significantly lower for the EVBL group: odds ratio (OR) 2.06, 95% confidence interval (CI) [1.55-2.73], p < 0.0001, without evidence of publication bias. Bleeding rates were also significantly lower at 18 months (OR 2.20, 95% CI [1.04-4.60], P = 0.04), but publication bias was detected. When only high quality trials were taken into account, results for bleeding rates were no longer significant. No significant difference was found for either bleeding-related mortality or for all-cause mortality overall or at 6, 12, 18 or 24 months. BB were associated with more frequent severe adverse events (OR 2.61, 95% CI 1.60-4.40, P < 0.0001) whereas fatal adverse events were more frequent with EVBL (OR 0.14, 95% CI 0.02-0.99, P = 0.05).
CONCLUSION: EVBL appears to be superior to BB in preventing the first variceal bleed, although this finding may be biased as it was not confirmed by high quality trials. No difference was found for mortality. Current evidence is insufficient to recommend EVBL over BB as first-line therapy.
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. 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). 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. Randomised trials were included irrespective of publication status, blinding, and language. 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. 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. 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.[CINAHL Note: The Cochrane Collaboration systematic reviews contain interactive software that allows various calculations in the MetaView.]
