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Beta-blockers in cirrhosis: Evidence-based indications and limitations.

ABSTRACT: Non-selective beta-blockers (NSBBs) are the mainstay of treatment for portal hypertension in the setting of liver cirrhosis. Randomised controlled trials demonstrated their efficacy in preventing initial variceal bleeding and subsequent rebleeding. Recent evidence indicates that NSBBs could prevent liver decompensation in patients with compensated cirrhosis. Despite solid data favouring NSBB use in cirrhosis, some studies have highlighted relevant safety issues in patients with end-stage liver disease, particularly with refractory ascites and infection. This review summarises the evidence supporting current recommendations and restrictions of NSBB use in patients with cirrhosis.

SUBMITTER: Rodrigues SG

PROVIDER: S-EPMC7005550 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Beta-blockers in cirrhosis: Evidence-based indications and limitations.

Rodrigues Susana G SG Mendoza Yuly P YP Bosch Jaime J

JHEP reports : innovation in hepatology 20191220 1

Non-selective beta-blockers (NSBBs) are the mainstay of treatment for portal hypertension in the setting of liver cirrhosis. Randomised controlled trials demonstrated their efficacy in preventing initial variceal bleeding and subsequent rebleeding. Recent evidence indicates that NSBBs could prevent liver decompensation in patients with compensated cirrhosis. Despite solid data favouring NSBB use in cirrhosis, some studies have highlighted relevant safety issues in patients with end-stage liver d ...[more]

PMID: 32039404

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Blunted cardiovascular effects of beta-blockers in patients with cirrhosis: Relation to severity?

Project description:AimsPatients with cirrhosis and portal hypertension are at high risk of developing complications such as variceal hemorrhage, ascites, and cardiac dysfunction, the latter of which is known as cirrhotic cardiomyopathy. Since non-selective beta-blockers (NSBB) may aggravate hemodynamic complications we investigated the effect of real-time propranolol infusion on cardiac function in patients with varying degrees of cirrhosis.MethodsThirty-eight patients with Child-Pugh A (n = 17), B (n = 17) and C (n = 4) underwent liver vein catheterization and cardiac magnetic resonance imaging. We assessed the effect of real-time propranolol infusion on the hepatic venous pressure gradient, cardiac index, stroke volume, ejection fraction, heart rate, and contractility.ResultsNineteen patients were classified as responders to beta-blocker therapy. In pooling Child-Pugh B and C patients, the reduction in cardiac index by beta-blockade was weaker than in Child-Pugh A patients (-8.5% vs. -20.5%, p = 0.043). The effect of NSBB on portal pressure was inversely correlated to changes in the left atrium where the left atrial volume changed by 4 mL±18 in responders compared to 15 mL±11 in non-responders (p = 0.03). Finally, the baseline ejection fraction correlated inversely with the reduction in portal pressure (r = -0.39, p = 0.02).ConclusionWe found the effect of beta-blockade on cardiac index in patients with advanced cirrhosis to be less potent than in patients with early cirrhosis, indicating that underlying cirrhotic cardiomyopathy increases, and the cardiac compensatory reserve becomes more compromised, with disease progression. The differential effects of beta-blockade in the left atrium may be used to predict the effect of beta-blockers on portal pressure, but further studies are needed to investigate this possibility.

| S-EPMC9239488 | biostudies-literature

Nonselective beta blockers, hepatic decompensation, and mortality in cirrhosis: A national cohort study.

Project description:Background and aimsLittle is known about the effectiveness of nonselective beta blockers (NSBBs) in preventing hepatic decompensation in routine clinical settings. We investigated whether NSBBs are associated with hepatic decompensation or liver-related mortality in a national cohort of veterans with Child-Turcotte-Pugh (CTP) A cirrhosis with no prior decompensations.Approach and resultsIn an active comparator, new user (ACNU) design, we created a cohort of new users of carvedilol ( n = 123) versus new users of selective beta blockers (SBBs) ( n = 561) and followed patients for up to 3 years. An inverse probability treatment weighting (IPTW) approach balanced demographic and clinical confounders. The primary analysis simulated intention-to-treat ("pseudo-ITT") with IPTW-adjusted Cox models; secondary analyses were pseudo-as-treated, and both were adjusted for baseline and time-updating drug confounders. Subgroup analyses evaluated NSBB effects by HCV viremia status, CTP class, platelet count, alcohol-associated liver disease (ALD) etiology, and age. In pseudo-ITT analyses of carvedilol versus SBBs, carvedilol was associated with a lower hazard of any hepatic decompensation (HR 0.59, 95% CI 0.42-0.83) and the composite outcome of hepatic decompensation/liver-related mortality (HR 0.56, 95% CI 0.41-0.76). Results were similar in pseudo-as-treated analyses (hepatic decompensation: HR 0.55, 95% CI 0.33-0.94; composite outcome: HR 0.62, 95% 0.38-1.01). In subgroup analyses, carvedilol was associated with lower hazard of primary outcomes in the absence of HCV viremia, higher CTP class and platelet count, younger age, and ALD etiology.ConclusionsThere is an ongoing need to noninvasively identify patients who may benefit from NSBBs for the prevention of hepatic decompensation.

| S-EPMC9877112 | biostudies-literature

Carvedilol versus traditional, non-selective beta-blockers for adults with cirrhosis and gastroesophageal varices.

Project description: Not available

| S-EPMC6517039 | biostudies-literature

Beta-blockers in hospitalised patients with cirrhosis and ascites: mortality and factors determining discontinuation and reinitiation.

Project description:BACKGROUND:It has been suggested that beta-blockers may increase mortality in patients with cirrhosis and refractory ascites but the effect of beta-blockers discontinuation or reinitiation has not been examined. AIMS:To compare, in hospitalised patients with cirrhosis and ascites, the effect of BB on survival and to examine the effect/predictors of beta-blockers discontinuation and reinitiation. METHODS:Sub-analysis of NACSELD (North American consortium for the study of end-stage liver disease, database containing prospective data on hospitalised patients with cirrhosis) data from 7 centres enrolling >100 patients with ascites. Data on BB discontinuation and reinitiation were collected by chart review. RESULTS:Seven hundred and sixteen patients, 307 (43%) on beta-blockers at admission and 366 (51%) with refractory ascites, were followed to death or hospital discharge. Beta-blocker use was associated with a lower white blood cell count at admission. Beta-blocker use in hospitalised patients with ascites was not associated with a higher mortality, even in those with refractory ascites. No significant changes in mean arterial pressure (MAP) were observed between groups. Discontinuation of beta-blockers (49%) was driven by low MAP, infection and acute kidney injury at time of discontinuation but was not associated with a higher mortality. Beta-blocker reinitiation occurred in 40% prior to discharge and was mainly driven by an increase in MAP. CONCLUSIONS:Beta-blocker use is safe in patients with cirrhosis and ascites (including those with refractory ascites) provided beta-blockers are discontinued in the presence of a low MAP and reinitiated once MAP reincreases. A potentially beneficial anti-inflammatory effect of beta-blockers is suggested.

| S-EPMC6016372 | biostudies-literature

Cerebral Protection Devices during Transcatheter Interventions: Indications, Benefits, and Limitations.

Project description:PURPOSE OF REVIEW:Stroke remains a devastating complication of cardiovascular interventions. This review is going to discuss stroke rates and outcomes in different cardiovascular procedures with a highlight on the current evidence for the use of cerebral protection devices (CPD). RECENT FINDINGS:Depending on the quality of neurological assessment, stroke occurs in up to 9.1% after TAVI, 3.9% after mitral clipping, 3.1% in LAAO patients, 0.4% after PCIs, and 1.8% after catheter ablation. CPDs are available for routine use. They are easy to use in most anatomies, feasible, and safe. Data on clinical impact and stroke reduction from RCTs are still missing. Most evidence for the routine use of CPDs exists in TAVI patients, who are at the highest risk. The PROTECTED TAVI RCT will shed more light on the clinical impact of CPD-use in TAVI patients. In other cardiovascular procedures like mitral clipping, PCIs, and ablation, the current data do not support the routine use of CPDs in these patients.

| S-EPMC7351861 | biostudies-literature

Portal pressure reductions induced by nonselective beta-blockers improve outcomes and decrease mortality in patients with cirrhosis with and without ascites.

Project description:Content available: Audio Recording.

| S-EPMC9306434 | biostudies-literature

Progesterone for the Prevention of Preterm Birth - an Update of Evidence-Based Indications.

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| S-EPMC6690740 | biostudies-literature

Beta blockers for elective surgery in elderly patients: population based, retrospective cohort study.

Project description:ObjectiveTo test whether atenolol (a long acting beta blocker) and metoprolol (a short acting beta blocker) are associated with equivalent reductions in risk for elderly patients undergoing elective surgery.DesignPopulation based, retrospective cohort analysis.SettingAcute care hospitals in Ontario, Canada, over one decade.ParticipantsConsecutive patients older than 65 who were admitted for elective surgery, without symptomatic coronary disease.Main outcome measureDeath or myocardial infarction.Results37,151 patients were receiving atenolol or metoprolol before surgery, of which the most common operations were orthopaedic or abdominal procedures. As expected, the two groups were similar in demographic characteristics, medical therapy, and type of surgery. 1038 patients experienced a myocardial infarction or died, a rate that was significantly lower for patients receiving atenolol than for those receiving metoprolol (2.5% v 3.2%, P < 0.001). The decreased risk with atenolol persisted after adjustment for measured demographic, medical, and surgical factors; extended to comparisons of other long acting and short acting beta blockers; was accentuated in analyses that focused on patients with the clearest evidence of beta blocker treatment; and reflected the immediate postoperative interval.ConclusionsPatients receiving metoprolol do not have as low a perioperative cardiac risk as patients receiving atenolol, in accord with possible acute withdrawal after missed doses.

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Faecal microbiota transplantation: indications, evidence and safety.

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| S-EPMC7186269 | biostudies-literature

Evidence-Based Development and Rationale for Once-Daily Rivaroxaban Dosing Regimens Across Multiple Indications.

Project description:BackgroundRivaroxaban, a direct factor Xa inhibitor, has been developed to meet clinical needs in a broad range of indications in adults: prevention of venous thromboembolism after elective hip or knee replacement surgery, treatment and secondary prevention of venous thromboembolism, prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation having one or more risk factors, and in Europe, prevention of atherothrombotic events after an acute coronary syndrome in patients with elevated cardiac biomarkers. However, the precise dose and regimen vary with the indication, leading to this effort to provide clarity concerning the appropriate use of rivaroxaban. This article reviews the clinical development program for rivaroxaban and summarizes the evidence for each approved, indication-specific dose regimen.ResultsAlthough initially investigated for twice-daily dosing, early observations, including the finding that the pharmacodynamic effects of rivaroxaban last longer than the elimination half-life, suggested that once-daily dosing might be attainable and effective. These observations were evaluated within the extensive phase II program, which, together with pharmacology studies, provides the evidence underpinning the selection of once-daily regimens for most, but not all, of the approved clinical indications for rivaroxaban.ConclusionThe evidence for each dosing regimen demonstrates that although pharmacology studies are of paramount importance, dose regimens must be subjected to careful empirical validation. Once-daily dosing was shown to be clinically appropriate for most rivaroxaban indications. Furthermore, a "one size fits all" approach to dosing frequency is unlikely to result in a regimen that yields optimal patient outcomes across different indications.

| S-EPMC4888194 | biostudies-literature

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