Improving primary prophylaxis of variceal bleeding by adapting therapy to the clinical stage of cirrhosis. A competing‐risk meta‐analysis of individual participant data-Reference-Cited by-同舟云学术

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

Published:2023-12-18 Issue:3 Volume:59 Page:306-321
ISSN:0269-2813
Container-title:Alimentary Pharmacology & Therapeutics
language:en
Short-container-title:Aliment Pharmacol Ther

Author:

Villanueva Càndid¹²^ORCID,Sapena Victor³⁴,Lo Gin‐Ho⁵^ORCID,Seo Yeon Seok⁶,Shah Hasnain Ali⁷,Singh Virendra⁸^ORCID,Tripathi Dhiraj⁹¹⁰¹¹^ORCID,Schepke Michael¹²,Gheorghe Cristian¹³,Bonilha Daniell Q.¹⁴,Jutabha Rome¹⁵¹⁶,Wang Huay‐Min¹⁷,Rodrigues Susana G.¹⁸,Brujats Anna¹,Lee Han Ah.⁶^ORCID,Azam Zahid¹⁹,Kumar Pramod⁸^ORCID,Hayes Peter C.¹¹,Sauerbruch Tilman²⁰,Chen Wen‐Chi⁵^ORCID,Iacob Speranta¹³^ORCID,Libera Ermelindo D.¹⁴,Jensen Dennis M.²¹²²²³^ORCID,Alvarado Edilmar¹²^ORCID,Torres Ferran³⁴,Bosch Jaume²¹⁸,

Affiliation:

1. Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona Barcelona Spain

2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) Barcelona Spain

3. Biostatistics Unit Medical School, Universitat Autònoma de Barcelona Barcelona Spain

4. Medical Statistics Core Facility IDIBAPS, Hospital Clinic Barcelona Spain

5. Division of Gastroenterology, Department of Medicine E‐Da Hospital, I‐Shou University Kaohsiung Taiwan

6. Division of Gastroenterology and Hepatology, Department of Internal Medicine Korea University College of Medicine Seoul Korea

7. Section of Gastroenterology Aga Khan University Karachi Pakistan

8. Department of Hepatology Post Graduate Institute of Medical Education and Research Chandigarh India

9. University Hospitals Birmingham NHS Foundation Trust Birmingham UK

10. Institute of Immunology and Immunotherapy University of Birmingham Birmingham UK

11. Department of Hepatology Royal Infirmary of Edinburgh Edinburgh UK

12. Helios Clinic Siegburg Department Gastroenterology and Hepatology Siegburg Germany

13. Center of Gastroenterology & Hepatology, Fundeni Clinical Institute "Carol Davila" University of Medicine Bucharest Romania

14. Department of Gastroenterology Federal University of São Paulo, State University of Campinas Campinas Brazil

15. University of Southern California (USC) School of Medicine Los Angeles USA

16. Keck School of Medicine of University of Southern California and Clinical Outreach and Development Los Angeles USA

17. Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital Kaohsiung Taiwan, Republic of China

18. University Clinic for Visceral Surgery and Medicine, Inselspital Bern University Hospital Bern Switzerland

19. National Institute of Liver & GI Diseases, Dow University of Health Sciences Karachi Pakistan

20. Department of Internal Medicine I University of Bonn Bonn Germany

21. Department of Medicine, Division of Digestive Diseases David Geffen School of Medicine at UCLA Los Angeles California USA

22. Center for the Health Sciences, Los Angeles Veterans Administration Greater Los Angeles Healthcare System Los Angeles California USA

23. Center for Ulcer Research and Education: Digestive Diseases Research Center

Abstract

ABSTRACTBackground & AimsNon‐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.MethodsBy 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.ResultsOf 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 (I2 = 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 (I2 = 0%). In decompensated patients, mortality risk was similar with EVL vs. NSBBs and with NSBBs+EVL vs. either monotherapy.ConclusionsIn 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.

Funder

Instituto de Salud Carlos III

Publisher

Wiley

Subject

Pharmacology (medical),Gastroenterology,Hepatology

Link

https://onlinelibrary.wiley.com/doi/pdf/10.1111/apt.17824

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