OBJECTIVE:
Non-selective beta blockers (NSBB) is the preferred treatment option for primary prophylaxis of high-risk esophageal varices, and endoscopic band ligation (EBL) is reserved for those intolerant to NSBB. However, the therapeutic choice can be challenging when high-risk varices are encountered in clinical practice. It appears combination therapy using EBL and NSBB would address the local and pathophysiological mechanism and decrease bleeding episodes better than either treatment alone. In this meta-analysis, we aim to compare the outcomes of NSBB, EBL and combination therapy for primary prophylaxis of high risk esophageal varices.
METHODS:
Major databases, such as MedLine, Embase, Web-of-Science were searched in October 2023 to identify studies comparing clinical outcomes between combination approaches versus NSBB versus EBL only. Only randomized controlled trials were included. Meta-analysis was performed using the random-effects model and heterogeneity was assessed by I²% statistics.
RESULTS
Seven trials were included in the study which comprised 1286 participants (68% males), with an average age of 51.6 ± 5.75 years. Among these studies, 6 out of 7 reported Child Pugh Class B and C in 29% and 13% patients, respectively. The NSBBs used were propranolol, nadolol, and carvedilol, with an average follow-up of 28.25 ± 23.45 months. The combination approach significantly reduced the first episode of variceal bleeding compared to NSBB (pooled Risk Ratio 0.4 [95% CI 0.2-0.7], p = 0.003) (Figure-1), while no significant difference was observed compared to EBL (pooled Risk Ratio 0.5 [95% CI 0.2-1.1], p = 0.07). Similarly, varices eradication was comparable between combined approach and EBL (RR: 0.99, 0.96-1.1). The pooled rate of bleeding with the combined approach was 6% (95% CI 3-11%, I²=57%), with NSBB was 20% (95% CI 9-38%, I²=92%), and with EBL was 11% (95% CI 6-17%, I²=24%). Pooled bleeding free survival with combined therapy was 55% (17-88) and with NSBB was 40% (10-80). Pooled RR approached significance [1.2, 0.97-1.6, P=0.07]. Bleeding-related mortality with combined therapy was 2% (0.9-4) and with NSBB was 3% (0.3-21), which also approached significance [RR: 0.4, 0.13-1.2, p=0.08].
All-cause mortality rates across groups were comparable (p-value > 0.05).
Pooled rates are summarized in Table-1.
CONCLUSIONS:
Based on this meta-analysis, primary prophylaxis of high-grade varices by combination therapy demonstrated a significantly lower risk of variceal bleeding. Bleeding rate was 6% with combination therapy as compared to 20% with NSBBs and 11% with EBL. Additionally, future research is warranted in identifying the right cohort of patients who might benefit the most with combination therapy.

Table 1: Pooled rates and proportions of the two groups

Figure 1: Forest plot. Variceal rebleeding: Combined approach versus NSBB

Daniel Lim

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