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Balloon Tamponade and Esophageal Stenting for Esophageal Variceal Bleeding in Cirrhosis: A Systematic Review and Meta-analysis
Rodrigues SG, Cardenas A, Escorsell A, Bosch J
Seminars in liver disease. 2019
Abstract
Failure to control variceal bleeding with current recommendations occurs in 10 to 20% of cases. This systematic review and meta-analysis analyzes the experience, results, and complications of "bridge" therapies for failure to control acute variceal bleeding: balloon tamponade and esophageal stents. The main outcomes assessed were failure to control bleeding and mortality in the short-term and medium-term follow-up, and adverse events. Balloon tamponade studies had a pooled rate of short-term failure to control bleeding of 35.5%, and adverse events in over 20% of cases; 9.7% resulting in death. Stenting failed to control bleeding in the short term and medium term in 12.7 and 21.5% of cases of severe or refractory variceal bleeding, respectively, despite stent migration in 23.8% of cases. Medium-term mortality rates were similar in both therapies. Although only one trial compared these treatments, the available evidence consistently supports that stents serve as a better and safer bridge therapy in refractory acute variceal bleeding.
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Stratifying risk in the prevention of recurrent variceal hemorrhage: results of an individual patient meta-analysis
Albillos A, Zamora J, Martinez J, Arroyo D, Ahmad I, De-la-Pena J, Garcia-Pagan JC, Lo GH, Sarin S, Sharma B, et al
Hepatology (Baltimore, Md.). 2017;66((4):):1219-1231
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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 vs. B/C) by means of individual time-to-event patient data meta-analysis (IPD) from randomized controlled trials. The study was IPD of 389 patients from 3 trials comparing EVL plus BB vs. BB and 416 patients from 4 trials comparing EVL plus BB vs. EVL. Compared with BB alone, EVL plus BB reduced overall rebleeding in Child A (incidence rate ratio 0.40; 95%CI 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%CI 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 since it is more effective in preventing rebleeding, without modifying survival. In patients with advanced liver failure (Child B/C), EVL alone carries an increased risk of rebleeding and death as compared with combination therapy, underlining that BB is the key element of combination therapy. This article is protected by copyright. All rights reserved.
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Effect of recombinant Factor VIIa on outcome of acute variceal bleeding: an individual patient based meta-analysis of two controlled trials
Bendtsen F, D'Amico G, Rusch E, de Franchis R, Andersen PK, Lebrec D, Thabut D, Bosch J
Journal of Hepatology. 2014;61((2)):252-9.
Abstract
BACKGROUND & AIMS Two randomized controlled studies have evaluated the effect of recombinant Factor VIIa (rFVIIa) on variceal bleeding in cirrhosis without showing significant benefit. The aim of the present study was to perform a meta-analysis of the two trials on individual patient data with special focus on high risk patients. METHODS The primary outcome measure was the effect of rFVIIa on a composite five day endpoint: failure to control bleeding, 5-day rebleeding or death. Analysis was based on intention to treat. High risk was defined as active bleeding on endoscopy while under vasoactive drug infusion and Child-Pugh score >8. RESULTS 497 patients were eligible for the meta-analysis; 308 (62%) had active variceal bleeding at endoscopy (oozing or spurting) and 283 of these had a Child-Pugh score >8. Analysis on the composite endpoint in all patients with bleeding from oesophageal varices did not show any beneficial treatment effect. However, failure rate for the primary composite end-point was significantly lower in treated patients with active bleeding at endoscopy (17%) compared to placebo (26%, p=0.049). This difference was highly significant in patients with Child-Pugh score >8 and active bleeding at endoscopy (rFVIIa 16%, placebo 27%; p=0.023). No significant treatment effect was found at 42 days. Five thromboembolic events occurred in rFVIIa treated patients compared to none in placebo treated patients. CONCLUSIONS The current meta-analysis shows a beneficial effect of rFVIIa on the primary composite endpoint of control of acute bleeding, prevention of rebleeding day 1-5 and 5-day mortality in patients with advanced cirrhosis and active bleeding from oesophageal varices at endoscopy. A major drawback of the treatment is a potential increased risk of arterial thrombo-embolic events. This treatment might be considered in patients with lack of control of bleeding after standard treatment.Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. RN 0 (Recombinant Proteins). 0 (recombinant FVIIa). EC 3-4-21-21 (Factor VIIa).
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Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized, controlled trial
Bosch J, Thabut D, Albillos A, Carbonell N, Spicak J, Massard J, D'Amico G, Lebrec D, de Franchis R, Fabricius S, et al
Hepatology (Baltimore, Md.). 2008;47((5):):1604-14.
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Abstract
A beneficial effect of recombinant activated factor VII (rFVIIa) in Child-Pugh class B and C patients with cirrhosis who have variceal bleeding has been suggested. This randomized controlled trial assessed the efficacy and safety of rFVIIa in patients with advanced cirrhosis and active variceal bleeding. At 31 hospitals in an emergency setting, 256 patients (Child-Pugh > 8; Child-Pugh B = 26%, C = 74%) were randomized equally to: placebo; 600 microg/kg rFVIIa (200 + 4x 100 microg/kg); or 300 microg/kg rFVIIa (200 + 100 microg/kg). Dosing was intravenous at 0, 2, 8, 14, and 20 hours after endoscopy, in addition to standard vasoactive, prophylactic antibiotic, and endoscopic treatment. The primary composite endpoint consisted of failure to control 24-hour bleeding, or failure to prevent rebleeding or death at day 5. Secondary endpoints included adverse events and 42-day mortality. Baseline characteristics were comparable between groups. Administration of rFVIIa had no significant effect on the composite endpoint compared with placebo (P = 0. 37). There was no significant difference in 5-day mortality between groups; however, 42-day mortality was significantly lower with 600 microg/kg rFVIIa compared with placebo (odds ratio 0. 31, 95% confidence interval = 0. 13-0. 74), and bleeding-related deaths were reduced from 12% (placebo) to 2% (600 microg/kg). A marked heterogeneity in the failure rate in all treatment groups was observed across participating centers. Adverse events, including overall thromboembolic events, were comparable between groups. CONCLUSION Treatment with rFVIIa had no significant effect on the primary composite endpoint compared with placebo. Therefore, decision on the use of this hemostatic agent in acute variceal bleeding should be carefully considered, because results of this study do not support the routine use of rFVIIa in this setting. Adverse events were comparable across groups.
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Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: a randomized, double-blind trial
Bosch J, Thabut D, Bendtsen F, D'Amico G, Albillos A, González Abraldes J, Fabricius S, Erhardtsen E, de Franchis R, European Study Group on rFVIIa in UGI Haemorrhage
Gastroenterology. 2004;127((4):):1123-30.
Abstract
BACKGROUND & AIMS Upper gastrointestinal bleeding (UGIB) is a severe and frequent complication of cirrhosis. Recombinant coagulation factor VIIa (rFVIIa) has been shown to correct the prolonged prothrombin time in patients with cirrhosis and UGIB. This trial aimed to determine efficacy and safety of rFVIIa in cirrhotic patients with variceal and nonvariceal UGIB. METHODS A total of 245 cirrhotic patients (Child-Pugh < 13; Child-Pugh A = 20%, B = 52%, C = 28%) with UGIB (variceal = 66%, nonvariceal = 29%, bleeding source unknown = 5%) were randomized equally to receive 8 doses of 100 microg/kg rFVIIa or placebo in addition to pharmacologic and endoscopic treatment. The primary end point was a composite including: (1) failure to control UGIB within 24 hours after first dose, or (2) failure to prevent rebleeding between 24 hours and day 5, or (3) death within 5 days. RESULTS Baseline characteristics were similar between rFVIIa and placebo groups. rFVIIa showed no advantage over standard treatment in the whole trial population. Exploratory analyses, however, showed that rFVIIa significantly decreased the number of failures on the composite end point (P = 0. 03) and the 24-hour bleeding control end point (P = 0. 01) in the subgroup of Child-Pugh B and C variceal bleeders. There were no significant differences between rFVIIa and placebo groups in mortality (5- or 42-day) or incidence of adverse events including thromboembolic events. CONCLUSIONS Although no overall effect of rFVIIa was observed, exploratory analyses in Child-Pugh B and C cirrhotic patients indicated that administration of rFVIIa significantly decreased the proportion of patients who failed to control variceal bleeding. Dosing with rFVIIa appeared safe. Further studies are needed to verify these findings.