Stratifying risk in the prevention of recurrent variceal hemorrhage: Results of an individual patient meta-analysis

on behalf of the Baveno Cooperation

doi:10.1002/hep.29267

Stratifying risk in the prevention of recurrent variceal hemorrhage: Results of an individual patient meta-analysis

on behalf of the Baveno Cooperation

Metabolism and Systems Research

Research output: Contribution to journal › Article › peer-review

65 Citations (Scopus)

Abstract

Endoscopic variceal ligation plus beta-blockers (EVL+BB) is currently recommended for variceal rebleeding prophylaxis, a recommendation that extends to all patients with cirrhosis with previous variceal bleeding irrespective of prognostic stage. Individualizing patient care is relevant, and in published studies on variceal rebleeding prophylaxis, there is a lack of information regarding response to therapy by prognostic stage. This study aimed at comparing EVL plus BB with monotherapy (EVL or BB) on all-source rebleeding and mortality in patients with cirrhosis and previous variceal bleeding stratified by cirrhosis severity (Child A versus B/C) by means of individual time-to-event patient data meta-analysis from randomized controlled trials. The study used individual data on 389 patients from three trials comparing EVL plus BB versus BB and 416 patients from four trials comparing EVL plus BB versus EVL. Compared with BB alone, EVL plus BB reduced overall rebleeding in Child A (incidence rate ratio 0.40; 95% confidence interval, 0.18-0.89; P = 0.025) but not in Child B/C, without differences in mortality. The effect of EVL on rebleeding was different according to Child (P for interaction <0.001). Conversely, compared with EVL, EVL plus BB reduced rebleeding in both Child A and B/C, with a significant reduction in mortality in Child B/C (incidence rate ratio 0.46; 95% confidence interval, 0.25-0.85; P = 0.013). Conclusion: Outcomes of therapies to prevent variceal rebleeding differ depending on cirrhosis severity: in patients with preserved liver function (Child A), combination therapy is recommended because it is more effective in preventing rebleeding, without modifying survival, while in patients with advanced liver failure (Child B/C), EVL alone carries an increased risk of rebleeding and death compared with combination therapy, underlining that BB is the key element of combination therapy. (Hepatology 2017;66:1219-1231).

Original language	English
Pages (from-to)	1219-1231
Number of pages	13
Journal	Hepatology
Volume	66
Issue number	4
DOIs	https://doi.org/10.1002/hep.29267
Publication status	Published - Oct 2017

Bibliographical note

Funding Information:
Received November 30, 2016; accepted May 15, 2017. Additional Supporting Information may be found at onlinelibrary.wiley.com/doi/10.1002/hep.29267/suppinfo. *These authors contributed equally to this work. Supported by the Spanish Ministry of Health, Instituto de Salud Carlos III–Spain (Plan Estatal de I1D1I 2013-2016) (PI14/00876, PI051871, to A.A. and CIBEREHD; PI13/00896, to J.V. and CIBERESP), cofinanced by the European Development Regional Fund “A Way to Achieve Europe” (ERDF), and by the National Institutes of Health (P30 DK34989, to G.G.-T.). Copyright VC 2017 by the American Association for the Study of Liver Diseases. View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.29267

Publisher Copyright:
© 2017 by the American Association for the Study of Liver Diseases.

ASJC Scopus subject areas

Hepatology

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10.1002/hep.29267

Cite this

@article{1e8163cb59844d64875d6b7c53e9b083,

title = "Stratifying risk in the prevention of recurrent variceal hemorrhage: Results of an individual patient meta-analysis",

abstract = "Endoscopic variceal ligation plus beta-blockers (EVL+BB) is currently recommended for variceal rebleeding prophylaxis, a recommendation that extends to all patients with cirrhosis with previous variceal bleeding irrespective of prognostic stage. Individualizing patient care is relevant, and in published studies on variceal rebleeding prophylaxis, there is a lack of information regarding response to therapy by prognostic stage. This study aimed at comparing EVL plus BB with monotherapy (EVL or BB) on all-source rebleeding and mortality in patients with cirrhosis and previous variceal bleeding stratified by cirrhosis severity (Child A versus B/C) by means of individual time-to-event patient data meta-analysis from randomized controlled trials. The study used individual data on 389 patients from three trials comparing EVL plus BB versus BB and 416 patients from four trials comparing EVL plus BB versus EVL. Compared with BB alone, EVL plus BB reduced overall rebleeding in Child A (incidence rate ratio 0.40; 95% confidence interval, 0.18-0.89; P = 0.025) but not in Child B/C, without differences in mortality. The effect of EVL on rebleeding was different according to Child (P for interaction <0.001). Conversely, compared with EVL, EVL plus BB reduced rebleeding in both Child A and B/C, with a significant reduction in mortality in Child B/C (incidence rate ratio 0.46; 95% confidence interval, 0.25-0.85; P = 0.013). Conclusion: Outcomes of therapies to prevent variceal rebleeding differ depending on cirrhosis severity: in patients with preserved liver function (Child A), combination therapy is recommended because it is more effective in preventing rebleeding, without modifying survival, while in patients with advanced liver failure (Child B/C), EVL alone carries an increased risk of rebleeding and death compared with combination therapy, underlining that BB is the key element of combination therapy. (Hepatology 2017;66:1219-1231).",

author = "{on behalf of the Baveno Cooperation} and Agust{\'i}n Albillos and Javier Zamora and Javier Mart{\'i}nez and David Arroyo and Irfan Ahmad and Joaquin De-la-Pe{\~n}a and Garcia-Pag{\'a}n, {Juan Carlos} and Lo, {Gin Ho} and Shiv Sarin and Barjesh Sharma and Abraldes, {Juan G.} and Jaime Bosch and Guadalupe Garcia-Tsao",

note = "Funding Information: Received November 30, 2016; accepted May 15, 2017. Additional Supporting Information may be found at onlinelibrary.wiley.com/doi/10.1002/hep.29267/suppinfo. *These authors contributed equally to this work. Supported by the Spanish Ministry of Health, Instituto de Salud Carlos III–Spain (Plan Estatal de I1D1I 2013-2016) (PI14/00876, PI051871, to A.A. and CIBEREHD; PI13/00896, to J.V. and CIBERESP), cofinanced by the European Development Regional Fund “A Way to Achieve Europe” (ERDF), and by the National Institutes of Health (P30 DK34989, to G.G.-T.). Copyright VC 2017 by the American Association for the Study of Liver Diseases. View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.29267 Publisher Copyright: {\textcopyright} 2017 by the American Association for the Study of Liver Diseases.",

year = "2017",

month = oct,

doi = "10.1002/hep.29267",

language = "English",

volume = "66",

pages = "1219--1231",

journal = "Hepatology",

issn = "0270-9139",

publisher = "Wiley",

number = "4",

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TY - JOUR

T1 - Stratifying risk in the prevention of recurrent variceal hemorrhage

T2 - Results of an individual patient meta-analysis

AU - on behalf of the Baveno Cooperation

AU - Albillos, Agustín

AU - Zamora, Javier

AU - Martínez, Javier

AU - Arroyo, David

AU - Ahmad, Irfan

AU - De-la-Peña, Joaquin

AU - Garcia-Pagán, Juan Carlos

AU - Lo, Gin Ho

AU - Sarin, Shiv

AU - Sharma, Barjesh

AU - Abraldes, Juan G.

AU - Bosch, Jaime

AU - Garcia-Tsao, Guadalupe

N1 - Funding Information: Received November 30, 2016; accepted May 15, 2017. Additional Supporting Information may be found at onlinelibrary.wiley.com/doi/10.1002/hep.29267/suppinfo. *These authors contributed equally to this work. Supported by the Spanish Ministry of Health, Instituto de Salud Carlos III–Spain (Plan Estatal de I1D1I 2013-2016) (PI14/00876, PI051871, to A.A. and CIBEREHD; PI13/00896, to J.V. and CIBERESP), cofinanced by the European Development Regional Fund “A Way to Achieve Europe” (ERDF), and by the National Institutes of Health (P30 DK34989, to G.G.-T.). Copyright VC 2017 by the American Association for the Study of Liver Diseases. View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.29267 Publisher Copyright: © 2017 by the American Association for the Study of Liver Diseases.

PY - 2017/10

Y1 - 2017/10

N2 - Endoscopic variceal ligation plus beta-blockers (EVL+BB) is currently recommended for variceal rebleeding prophylaxis, a recommendation that extends to all patients with cirrhosis with previous variceal bleeding irrespective of prognostic stage. Individualizing patient care is relevant, and in published studies on variceal rebleeding prophylaxis, there is a lack of information regarding response to therapy by prognostic stage. This study aimed at comparing EVL plus BB with monotherapy (EVL or BB) on all-source rebleeding and mortality in patients with cirrhosis and previous variceal bleeding stratified by cirrhosis severity (Child A versus B/C) by means of individual time-to-event patient data meta-analysis from randomized controlled trials. The study used individual data on 389 patients from three trials comparing EVL plus BB versus BB and 416 patients from four trials comparing EVL plus BB versus EVL. Compared with BB alone, EVL plus BB reduced overall rebleeding in Child A (incidence rate ratio 0.40; 95% confidence interval, 0.18-0.89; P = 0.025) but not in Child B/C, without differences in mortality. The effect of EVL on rebleeding was different according to Child (P for interaction <0.001). Conversely, compared with EVL, EVL plus BB reduced rebleeding in both Child A and B/C, with a significant reduction in mortality in Child B/C (incidence rate ratio 0.46; 95% confidence interval, 0.25-0.85; P = 0.013). Conclusion: Outcomes of therapies to prevent variceal rebleeding differ depending on cirrhosis severity: in patients with preserved liver function (Child A), combination therapy is recommended because it is more effective in preventing rebleeding, without modifying survival, while in patients with advanced liver failure (Child B/C), EVL alone carries an increased risk of rebleeding and death compared with combination therapy, underlining that BB is the key element of combination therapy. (Hepatology 2017;66:1219-1231).

AB - Endoscopic variceal ligation plus beta-blockers (EVL+BB) is currently recommended for variceal rebleeding prophylaxis, a recommendation that extends to all patients with cirrhosis with previous variceal bleeding irrespective of prognostic stage. Individualizing patient care is relevant, and in published studies on variceal rebleeding prophylaxis, there is a lack of information regarding response to therapy by prognostic stage. This study aimed at comparing EVL plus BB with monotherapy (EVL or BB) on all-source rebleeding and mortality in patients with cirrhosis and previous variceal bleeding stratified by cirrhosis severity (Child A versus B/C) by means of individual time-to-event patient data meta-analysis from randomized controlled trials. The study used individual data on 389 patients from three trials comparing EVL plus BB versus BB and 416 patients from four trials comparing EVL plus BB versus EVL. Compared with BB alone, EVL plus BB reduced overall rebleeding in Child A (incidence rate ratio 0.40; 95% confidence interval, 0.18-0.89; P = 0.025) but not in Child B/C, without differences in mortality. The effect of EVL on rebleeding was different according to Child (P for interaction <0.001). Conversely, compared with EVL, EVL plus BB reduced rebleeding in both Child A and B/C, with a significant reduction in mortality in Child B/C (incidence rate ratio 0.46; 95% confidence interval, 0.25-0.85; P = 0.013). Conclusion: Outcomes of therapies to prevent variceal rebleeding differ depending on cirrhosis severity: in patients with preserved liver function (Child A), combination therapy is recommended because it is more effective in preventing rebleeding, without modifying survival, while in patients with advanced liver failure (Child B/C), EVL alone carries an increased risk of rebleeding and death compared with combination therapy, underlining that BB is the key element of combination therapy. (Hepatology 2017;66:1219-1231).

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DO - 10.1002/hep.29267

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ER -

Stratifying risk in the prevention of recurrent variceal hemorrhage: Results of an individual patient meta-analysis

Abstract

Bibliographical note

ASJC Scopus subject areas

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