The authors concluded that endoscopic variceal banding ligation appeared to be superior to beta-blockers in preventing the first variceal bleed but this finding was not supported by high quality studies. This was a well-conducted review and the authors' conclusions are likely to be reliable. The conclusions did not address the results relating to adverse events.

To compare beta-blockers with endoscopic variceal banding ligation (EVBL) in the primary prophylaxis of oesophageal variceal bleeding.

MEDLINE, Web of Science, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched up to June 2011; the search strategy and terms were reported. There was a manual search of conference abstracts, trial registries and reference lists of articles and reviews. There were no language restrictions.

Randomised controlled trials (RCTs), including full papers and abstracts, that compared beta-blockers with EVBL for primary prophylaxis of first oesophageal variceal bleeding were eligible for inclusion. Participants had to have oesophageal varices secondary to portal hypertension with no evidence of prior variceal bleeding. The main outcomes of interest were variceal bleeding rates and all-cause mortality.

All of the trials except one included patients with portal hypertension due to proven cirrhosis. Mean ages ranged from 39 to 62 years. Most patients were male. Varices were mostly grade II in four trials, grade III in four trials and grade IV in one trial. All trials except one trial used propranolol (mean daily dose ranged from 30mg to 113.5mg); the other trial used nadolol. Follow-up of ranged from 10 to 55 months.

The authors did not state how many reviewers selected studies for inclusion.

Study quality was assessed with criteria recommended in the Cochrane Handbook of Systematic Reviews of Interventions for adequate sequence generation, allocation concealment, selective outcome reporting, handling of incomplete data, intention-to-treat analysis and sample size calculation. Each criterion was evaluated as high, low or unclear risk of bias.

Studies were quality assessed by two independent reviewers and any discrepancies were resolved by discussion.

Primary (variceal bleeding rates and all-cause mortality) and secondary outcomes (bleeding-related mortality and adverse events) were extracted from each study to calculate odds ratios with 95% confidence intervals (CIs). Data for the primary outcomes were extracted at different time points (six, 12, 18 and 24 months). Where possible, missing data were requested from study authors. Where this was not available, three independent reviewers extrapolated data from Kaplan-Meier survival curves and averaged their results.

Data were extracted by two independent reviewers and any discrepancies were resolved by discussion.

The studies were pooled using both fixed-effect and random-effects models (the latter model was used when there was significant heterogeneity). Heterogeneity was calculated using Breslow-Day's test and Ι². Publication bias was assessed using the Egger test, Duval and Tweedie's trim and fill method and the fail safe number according to Orwin's formula.

Subgroup analysis was conducted according to dose of beta-blockers (low versus high) and length of interval between banding sessions (short versus long). Sensitivity analysis was conducted on the primary outcomes according to the quality of the studies.

Nineteen RCTs were included in the review (1,483 patients). Fourteen trials were considered to be at high risk of bias and five were considered to be at low risk of bias.

Bleeding was significantly lower in the EVBL group compared to beta-blockers (OR 2.06, 95% CI 1.55 to 2.73; 19 trials) with no significant heterogeneity and no evidence of publication bias. A tendency towards reduced bleeding was found at all time points but the difference was significant only at 18 months (OR 2.20, 95% CI 1.04 to 4.60). Subgroup analysis demonstrated that high dose was no longer significant overall and low dose was significant at all time points except 24 months. Subgroup analysis by length of the interval between banding ligation sessions found that bleeding rates were also significantly lower at 12, 18 and 24 months for studies with a long interval. When only high quality studies were included in the analysis there was no significant difference in bleeding rates between groups overall or at any time point.

There was no significant difference between treatment groups for all-cause mortality (seventeen trials) and bleeding-related mortality. There was a tendency towards lower all-cause mortality rates in the beta-blockers group at shorter follow-up (six months). The results for both analyses did not differ when quality of the studies was considered.

Severe adverse events were significantly more frequent in patients who took beta-blockers compared to EVBL (OR 2.61, 95% CI 1.60 to 4.40; no statistical heterogeneity). Patients in the EVBL group had a significantly higher number of fatal adverse events (OR 0.14, 95% CI 0.02 to 0.99; no statistical heterogeneity).

EVBL appeared to be superior to beta-blockers in preventing the first variceal bleed in cirrhotic patients but this result was not confirmed when only high quality studies were taken into account.

The review question and inclusion criteria were clear. Several sources were searched for relevant studies. The authors found no evidence of publication bias. Two reviewers extracted data, which reduced the risk for reviewer bias. Quality of the trials was assessed using appropriate methods and the results of this assessment were considered in the analyses. Pooling of the studies was appropriately undertaken and suitable methods were used to assess heterogeneity.

This was a well-conducted review and the authors' conclusions are likely to be reliable. The conclusions did not address the results relating to adverse events.

Practice: The authors stated that evidence was insufficient to recommend EVBL as first-line therapy over beta-blockers. They stated that EVBL should be proposed to patients who were non-compliant, had contra-indications or poorly tolerated beta-blocker therapy.

Research: The authors stated that further high quality studies were needed to assess the superiority of EVBL over beta-blockers for bleeding-rates.

None.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.