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Improving primary prophylaxis of variceal bleeding by adapting therapy to the clinical stage of cirrhosis. A competing-risk meta-analysis of individual participant data.

Abstract:

BACKGROUND & AIMS

Non-selective β-blockers (NSBBs) and endoscopic variceal-ligation (EVL) have similar efficacy preventing first variceal bleeding. Compensated and decompensated cirrhosis are markedly different stages, which may impact treatment outcomes. We aimed to assess the efficacy of NSBBs vs EVL on survival in patients with high-risk varices without previous bleeding, stratifying risk according to compensated/decompensated stage of cirrhosis.

METHODS

By systematic review, we identified RCTs comparing NSBBs vs EVL, in monotherapy or combined, for primary bleeding prevention. We performed a competing-risk, time-to-event meta-analysis, using individual patient data (IPD) obtained from principal investigators of RCTs. Analyses were stratified according to previous decompensation of cirrhosis.

RESULTS

Of 25 RCTs eligible, 14 failed to provide IPD and 11 were included, comprising 1400 patients (656 compensated, 744 decompensated), treated with NSBBs (N = 625), EVL (N = 546) or NSBB+EVL (N = 229). Baseline characteristics were similar between groups. Overall, mortality risk was similar with EVL vs. NSBBs (subdistribution hazard-ratio (sHR) = 1.05, 95% CI = 0.75-1.49) and with EVL + NSBBs vs either monotherapy, with low heterogeneity (I  = 28.7%). In compensated patients, mortality risk was higher with EVL vs NSBBs (sHR = 1.76, 95% CI = 1.11-2.77) and not significantly lower with NSBBs+EVL vs NSBBs, without heterogeneity (I  = 0%). In decompensated patients, mortality risk was similar with EVL vs. NSBBs and with NSBBs+EVL vs. either monotherapy.

CONCLUSIONS

In patients with compensated cirrhosis and high-risk varices on primary prophylaxis, NSBBs significantly improved survival vs EVL, with no additional benefit noted adding EVL to NSBBs. In decompensated patients, survival was similar with both therapies. The study suggests that NSBBs are preferable when advising preventive therapy in compensated patients.

© 2023 John Wiley & Sons Ltd.

Keywords: clinically significant portal hypertension, complications of cirrhosis, endoscopic variceal ligation, prevention of cirrhosis decompensation, primary prophylaxis, β-Blockers

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Authors

Journal Title: Alimentary pharmacology & therapeutics

Journal ISSN: 1365-2036

Journal ISO Abbreviation: Aliment Pharmacol Ther

Publication Date: 2024-02-01

DOI: 10.1111/apt.17824

Volume: 59

Issue: 3

Start Page: 306

End Page: 321