Improving primary prophylaxis of variceal bleeding by adapting therapy to the clinical stage of cirrhosis. A competing‐risk meta‐analysis of individual participant data
Càndid Villanueva, Víctor Sapena, Gin‐Ho Lo, Yeon Seok Seo, Hasnain Ali Shah, Virendra Singh, Dhiraj Tripathi, Michael Schepke, Cristian Gheorghe, Daniell Q. Bonilha, Rome Jutabha, Huay‐Min Wang, Susana Rodrigues, Anna Brujats, Han Ah Lee, Zahid Azam, Pramod Kumar, Peter Hayes, Tilman Sauerbruch, Wen‐Chi Chen, Speranta Iacob, Ermelindo Della Líbera, Dennis M. Jensen, Edilmar Alvarado, Ferràn Torres, Jaime Bosch
Abstract
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 2 = 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 2 = 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.