Primary prevention of variceal bleeding in people with oesophageal varices due to liver cirrhosis: a network meta-analysis

Roccarina, Davide; Best, Lawrence; Freeman, Suzanne C.; Roberts, Danielle; Cooper, Nicola J.; Sutton, Alex J.; Benmassaoud, Amine; Torres, Maria Corina Plaz; Prat, Laura Iogna; Csenar, Mario; Arunan, Sivapatham; Begum, Tanjia; Milne, EJ; Tapp, Maxine; Pavlov, Chavdar S; Davidson, Brian R; Tsochatzis, Emmanuel; Williams, Norman; Gurusamy, Kurinchi Selvan

doi:10.1002/14651858.cd013121.pub2

Cited by 12 publications

(7 citation statements)

References 282 publications

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“…An additional positive effect was observed by adding ligation of varices (only one trial), but there were more serious adverse events in the banding groups as compared to monotherapy with NSBB. The evidence for these findings are classified as uncertain, mainly because of low number of cases in the individual trials and the quality of the studies ( 120 ).…”

Section: Indications For Nsbbs Results From Randomized Trialsmentioning

confidence: 99%

“…In the first meta-analysis ( 119 ) of individual patient data (589 pts from 4 RCT) 2-year-survival was similar (68% placebo vs. 71% NSBBs). A significant beneficial effect on survival in the setting of primary bleeding prophylaxis as compared to no active intervention was described in a very recent network-meta-analysis on 6,653 patients, however with only marginal differences when NSBBs were compared to variceal ligation with and without additional NSBBs ( 120 ). A competing risk meta-analysis of 11 RCT trials comprising individual data of 1,400 patients in the setting of prevention of bleeding from high risk varices showed that NSBBs alone or in combination with ligation achieved a better survival than ligation alone in patients with compensated cirrhosis, but not in patients with decompensated cirrhosis ( 121 ).…”

Section: Indications For Nsbbs Results From Randomized Trialsmentioning

confidence: 99%

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Beta-blockers in patients with liver cirrhosis: Pragmatism or perfection?

et al. 2023

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With increasing decompensation, hyperdynamic circulatory disturbance occurs in liver cirrhosis despite activation of vasoconstrictors. Here, the concept of a therapy with non-selective beta-blockers was established decades ago. They lower elevated portal pressure, protect against variceal hemorrhage, and may also have pleiotropic immunomodulatory effects. Recently, the beneficial effect of carvedilol, which blocks alpha and beta receptors, has been highlighted. Carvedilol leads to “biased-signaling” via recruitment of beta-arrestin. This effect and its consequences have not been sufficiently investigated in patients with liver cirrhosis. Also, a number of questions remain open regarding the expression of beta-receptors and its intracellular signaling and the respective consequences in the intra- and extrahepatic tissue compartments. Despite the undisputed role of non-selective beta-blockers in the treatment of liver cirrhosis, we still can improve the knowledge as to when and how beta-blockers should be used in which patients.

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Section: Indications For Nsbbs Results From Randomized Trialsmentioning

confidence: 99%

Section: Indications For Nsbbs Results From Randomized Trialsmentioning

confidence: 99%

Beta-blockers in patients with liver cirrhosis: Pragmatism or perfection?

et al. 2023

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“…In light of the evidence available, we gave moderate strength to the neutral and optimistic priors. Regarding the neutral prior, this was for the following reasons: first, there was no clear signal from the meta-analysis of primary prevention studies for the reduction in non-bleeding decompensation with beta-blocker treatment, 20 and second there was clinical equipoise at the time the trial commenced regarding a beneficial effect of NSBB in compensated cirrhosis for the prevention of non-bleeding decompensation. In addition, in preparation for these analyses, we also undertook a post hoc analysis of a major primary prevention study in persons with large varices considering only those without decompensation at baseline 8 .…”

Section: Methodsmentioning

confidence: 99%

Quantifying the benefit of nonselective beta-blockers in the prevention of hepatic decompensation: A Bayesian reanalysis of the PREDESCI trial

Rowe¹,

Villanueva²,

Shearer³

et al. 2023

Hepatology

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Background and Aims: Beta-blockers have been studied for the prevention of variceal bleeding and, more recently, for the prevention of all-cause decompensation. Some uncertainties regarding the benefit of beta-blockers for the prevention of decompensation remain. Bayesian analyses enhance the interpretation of trials. The purpose of this study was to provide clinically meaningful estimates of both the probability and magnitude of the benefit of beta-blocker treatment across a range of patient types.

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“…Based on low-certainty evidence, a Cochrane meta-analysis showed that beta-blockers, VBL, sclerotherapy and beta-blockers plus nitrates may decrease mortality compared with no intervention in cirrhotic patients with highrisk oesophageal varices without previous bleeding. 689 According to a systematic review with network metaanalysis, monotherapy with nonselective beta-blockers (NSBBs) may decrease all-cause mortality and the risk of first variceal bleeding in patients with cirrhosis with large oesophageal varices and carries a lower risk of serious complications compared with VBL. 690 In patients with refractory ascites or infection, data from observational studies are contradictory regarding the safety of NSBBs for primary prophylaxis of variceal bleeding, and the choice and doses of NSBBs should be individualised.…”

Section: Variceal Bleedingmentioning

confidence: 99%

Management of severe peri-operative bleeding: Guidelines from the European Society of Anaesthesiology and Intensive Care

Kietaibl

Ahmed

Afshari

et al. 2023

European Journal of Anaesthesiology

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BACKGROUND Management of peri-operative bleeding is complex and involves multiple assessment tools and strategies to ensure optimal patient care with the goal of reducing morbidity and mortality. These updated guidelines from the European Society of Anaesthesiology and Intensive Care (ESAIC) aim to provide an evidence-based set of recommendations for healthcare professionals to help ensure improved clinical management. DESIGN A systematic literature search from 2015 to 2021 of several electronic databases was performed without language restrictions. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to assess the methodological quality of the included studies and to formulate recommendations. A Delphi methodology was used to prepare a clinical practice guideline. RESULTS These searches identified 137 999 articles. All articles were assessed, and the existing 2017 guidelines were revised to incorporate new evidence. Sixteen recommendations derived from the systematic literature search, and four clinical guidances retained from previous ESAIC guidelines were formulated. Using the Delphi process on 253 sentences of guidance, strong consensus (>90% agreement) was achieved in 97% and consensus (75 to 90% agreement) in 3%. DISCUSSION Peri-operative bleeding management encompasses the patient's journey from the pre-operative state through the postoperative period. Along this journey, many features of the patient's pre-operative coagulation status, underlying comorbidities, general health and the procedures that they are undergoing need to be taken into account. Due to the many important aspects in peri-operative nontrauma bleeding management, guidance as to how best approach and treat each individual patient are key. Understanding which therapeutic approaches are most valuable at each timepoint can only enhance patient care, ensuring the best outcomes by reducing blood loss and, therefore, overall morbidity and mortality. CONCLUSION All healthcare professionals involved in the management of patients at risk for surgical bleeding should be aware of the current therapeutic options and approaches that are available to them. These guidelines aim to provide specific guidance for bleeding management in a variety of clinical situations.

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Primary prevention of variceal bleeding in people with oesophageal varices due to liver cirrhosis: a network meta-analysis

Abstract: Primary prevention of variceal bleeding in people with oesophageal varices due to liver cirrhosis: a network meta-analysis (Review)

Cited by 12 publications

References 282 publications

Beta-blockers in patients with liver cirrhosis: Pragmatism or perfection?

Beta-blockers in patients with liver cirrhosis: Pragmatism or perfection?

Quantifying the benefit of nonselective beta-blockers in the prevention of hepatic decompensation: A Bayesian reanalysis of the PREDESCI trial

Management of severe peri-operative bleeding: Guidelines from the European Society of Anaesthesiology and Intensive Care

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