NSBBs, EBL or Combined Therapy for High-Risk Varices: Systematic Review and Meta-Analysis

BACKGROUND AND AIMS: Non-selective beta blocker (NSBB) is the preferred treatment option for primary prophylaxis of high-risk oesophageal varices, and endoscopic band ligation (EBL) is reserved for those intolerant to NSBB. In this meta-analysis, we aim to compare the outcomes of NSBB, EBL and combined therapy for primary prophylaxis of high-risk oesophageal varices. METHODS: Major databases, such as MedLine, Embase and Cochrane Library were searched in October 2024 to identify studies comparing clinical outcomes between combined approaches versus NSBB versus EBL only. Only randomised trials were included. Meta-analysis was performed using the random-effects model, and heterogeneity was assessed by I2% statistics. RESULTS: Six randomised trials were included, which consisted of 1011 participants (NSBB 302, EBL 300 and 409 combined) (75.27% males), with an average age of 51.06 years. The NSBBs used were propranolol, nadolol and carvedilol, with an average follow-up of 17.54 months. The combined approach significantly reduced the first episode of variceal bleeding compared to NSBB alone (pooled RR 0.39 [95% CI 0.19-0.76], p = 0.009) and EBL alone (RR 0.46, 0.29-0.74; p = 0.002). The pooled rate of bleeding with the combined approach was 9.4% [95% CI 6%-14.3%], with NSBB being 28.2% [95% CI 12.9%-51%] and with EBL being 13.9% [6%-17%]. Pooled ratios for bleeding-related mortality were significantly better with the combined approach when compared to NSBB alone. CONCLUSION: Primary prophylaxis of high-grade varices by combined therapy demonstrated a significantly lower risk of variceal bleeding than NSBB or EBL alone. We recommend these findings be incorporated into forthcoming guidelines.