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The Cochrane Database of Systematic... Oct 2018Non-selective beta-blockers are recommended for the prevention of bleeding in people with cirrhosis, portal hypertension and gastroesophageal varices. Carvedilol is a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-selective beta-blockers are recommended for the prevention of bleeding in people with cirrhosis, portal hypertension and gastroesophageal varices. Carvedilol is a non-selective beta-blocker with additional intrinsic alpha-blocking effects, which may be superior to traditional, non-selective beta-blockers in reducing portal pressure and, therefore, in reducing the risk of upper gastrointestinal bleeding.
OBJECTIVES
To assess the beneficial and harmful effects of carvedilol compared with traditional, non-selective beta-blockers for adults with cirrhosis and gastroesophageal varices.
SEARCH METHODS
We combined searches in the Cochrane Hepato-Biliary's Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, and Science Citation Index with manual searches. The last search update was 08 May 2018.
SELECTION CRITERIA
We included randomised clinical trials comparing carvedilol versus traditional, non-selective beta-blockers, irrespective of publication status, blinding, or language. We included trials evaluating both primary and secondary prevention of upper gastrointestinal bleeding in adults with cirrhosis and verified gastroesophageal varices.
DATA COLLECTION AND ANALYSIS
Three review authors (AZ, RJ and LH), independently extracted data. The primary outcome measures were mortality, upper gastrointestinal bleeding and serious adverse events. We undertook meta-analyses and presented results using risk ratios (RR) or mean differences (MD), both with 95% confidence intervals (CIs), and I values as a marker of heterogeneity. We assessed bias control using the Cochrane Hepato-Biliary domains and the quality of the evidence with GRADE.
MAIN RESULTS
Eleven trials fulfilled our inclusion criteria. One trial did not report clinical outcomes. We included the remaining 10 randomised clinical trials, involving 810 participants with cirrhosis and oesophageal varices, in our analyses. The intervention comparisons were carvedilol versus propranolol (nine trials), or nadolol (one trial). Six trials were of short duration (mean 6 (range 1 to 12) weeks), while four were of longer duration (13.5 (6 to 30) months). Three trials evaluated primary prevention; three evaluated secondary prevention; while four evaluated both primary and secondary prevention. We classified all trials as at 'high risk of bias'. We gathered mortality data from seven trials involving 507 participants; no events occurred in four of these. Sixteen of 254 participants receiving carvedilol and 19 of 253 participants receiving propranolol or nadolol died (RR 0.86, 95% CI 0.48 to 1.53; I = 0%, low-quality evidence). There appeared to be no differences between carvedilol versus traditional, non-selective beta-blockers and the risks of upper gastrointestinal bleeding (RR 0.77, 95% CI 0.43 to 1.37; 810 participants; 10 trials; I = 45%, very low-quality evidence) and serious adverse events (RR 0.97, 95% CI 0.67 to 1.42; 810 participants; 10 trials; I = 14%, low-quality evidence). Significantly more deaths, episodes of upper gastrointestinal bleeding and serious adverse events occurred in the long-term trials but there was not enough information to determine whether there were differences between carvedilol and traditional, non-selective beta-blockers, by trial duration. There was also insufficient information to detect differences in the effects of these interventions in trials evaluating primary or secondary prevention. There appeared to be no differences in the risk of non-serious adverse events between carvedilol versus its comparators (RR 0.55, 95% CI 0.23 to 1.29; 596 participants; 6 trials; I = 88%; very low-quality evidence). Use of carvedilol was associated with a greater reduction in hepatic venous pressure gradient than traditional, non-selective beta-blockers both in absolute (MD -1.75 mmHg, 95% CI -2.60 to -0.89; 368 participants; 6 trials; I = 0%; low-quality evidence) and percentage terms (MD -8.02%, 95% CI -11.49% to -4.55%; 368 participants; 6 trials; I = 0%; low-quality evidence). However, we did not observe a concomitant reduction in the number of participants who failed to achieve a sufficient haemodynamic response (RR 0.76, 95% CI 0.57 to 1.02; 368 participants; 6 trials; I = 42%; very low-quality evidence) or in clinical outcomes.
AUTHORS' CONCLUSIONS
We found no clear beneficial or harmful effects of carvedilol versus traditional, non-selective beta-blockers on mortality, upper gastrointestinal bleeding, serious or non-serious adverse events despite the fact that carvedilol was more effective at reducing the hepatic venous pressure gradient. However, the evidence was of low or very low quality, and hence the findings are uncertain. Additional evidence is required from adequately powered, long-term, double-blind, randomised clinical trials, which evaluate both clinical and haemodynamic outcomes.
Topics: Adrenergic beta-Antagonists; Adult; Carvedilol; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Nadolol; Primary Prevention; Propranolol; Randomized Controlled Trials as Topic; Secondary Prevention
PubMed: 30372514
DOI: 10.1002/14651858.CD011510.pub2 -
BMJ Open May 2016To assess the clinical and haemodynamic effects of carvedilol for patients with cirrhosis and portal hypertension. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the clinical and haemodynamic effects of carvedilol for patients with cirrhosis and portal hypertension.
DESIGN
A systematic review and meta-analysis.
DATA SOURCES
We searched PubMed, Cochrane library databases, EMBASE and the Science Citation Index Expanded through December 2015. Only randomised controlled trials (RCTs) were included.
OUTCOME MEASURE
We calculated clinical outcomes (all-cause mortality, bleeding-related mortality, upper gastrointestinal bleeding) as well as haemodynamic outcomes (hepatic venous pressure (HVPG) reduction, haemodynamic response rate, post-treatment arterial blood pressure (mean arterial pressure; MAP) and adverse events).
RESULTS
12 RCTs were included. In 7 trials that looked at haemodynamic outcomes compared carvedilol versus propranolol, showing that carvedilol was associated with a greater reduction (%) of HVPG within 6 months (mean difference -8.49, 95% CI -12.36 to -4.63) without a greater reduction in MAP than propranolol. In 3 trials investigating differences in clinical outcomes between carvedilol versus endoscopic variceal band ligation (EVL), no significant differences in mortality or variceal bleeding were demonstrated. 1 trial compared clinical outcomes between carvedilol versus nadolol plus isosorbide-5-mononitrate (ISMN), and showed that no significant difference in mortality or bleeding had been found. 1 trial comparing carvedilol versus nebivolol showed a greater reduction in HVPG after 14 days follow-up in the carvedilol group.
CONCLUSIONS
Carvedilol may be more effective in decreasing HVPG than propranolol or nebivolol and it may be as effective as EVL or nadolol plus ISMN in preventing variceal bleeding. However, the overall quality of evidence is low. Further large-scale randomised studies are required before we can make firm conclusions.
TRIAL REGISTRATION NUMBER
CRD42015020542.
Topics: Antihypertensive Agents; Carbazoles; Carvedilol; Dose-Response Relationship, Drug; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hemodynamics; Humans; Hypertension, Portal; Liver Cirrhosis; Propanolamines; Propranolol; Treatment Outcome
PubMed: 27147389
DOI: 10.1136/bmjopen-2015-010902 -
Frontiers in Pharmacology 2023Hepatocellular carcinoma (HCC) is a serious complication of cirrhosis. Currently, non-selective beta-blockers (NSBBs) are commonly used to treat portal hypertension in...
Hepatocellular carcinoma (HCC) is a serious complication of cirrhosis. Currently, non-selective beta-blockers (NSBBs) are commonly used to treat portal hypertension in patients with cirrhosis. The latest research shows that NSBBs can induce apoptosis and S-phase arrest in liver cancer cells and inhibit the development of hepatic vascular endothelial cells, which may be effective in preventing HCC in cirrhosis patients. To determine the relationship between different NSBBs and HCC incidence in patients with cirrhosis. We searched the Cochrane database, MEDLINE, EMBASE, PubMed, and Web of Science. Cohort studies, case‒control studies, and randomized controlled trials were included if they involved cirrhosis patients who were divided into an experimental group using NSBBs and a control group with any intervention. Based on heterogeneity, we calculated odds ratio (OR) and 95% confidence interval (CI) using random-effect models. We also conducted subgroup analysis to explore the source of heterogeneity. Sensitivity analysis and publication bias detection were performed. A total of 47 studies included 38 reporting HCC incidence, 26 reporting HCC-related mortality, and 39 reporting overall mortality. The HCC incidence between the experimental group and the control group was OR = 0.87 (0.69 and 1.10), = 0.000, and I = 81.8%. There was no significant association between propranolol (OR = 0.94 and 95%CI 0.62-1.44) or timolol (OR = 1.32 and 95%CI 0.44-3.95) and HCC incidence, while the risk of HCC decreased by 26% and 38% with nadolol (OR = 0.74 and 95%CI 0.64-0.86) and carvedilol (OR = 0.62 and 95%CI 0.52-0.74), respectively. Different types of NSBB have different effects on the incidence of patients with cirrhosis of the liver, where nadolol and carvedilol can reduce the risk. Also, the effect of NSBBs may vary in ethnicity. Propranolol can reduce HCC incidence in Europe and America. identifier https://CRD42023434175, https://www.crd.york.ac.uk/PROSPERO/.
PubMed: 37538177
DOI: 10.3389/fphar.2023.1216059 -
Critical Care (London, England) Jun 2021β-adrenergic antagonists (BAAs) are used to treat cardiovascular disease such as ischemic heart disease, congestive heart failure, dysrhythmias, and hypertension....
BACKGROUND
β-adrenergic antagonists (BAAs) are used to treat cardiovascular disease such as ischemic heart disease, congestive heart failure, dysrhythmias, and hypertension. Poisoning from BAAs can lead to severe morbidity and mortality. We aimed to determine the utility of extracorporeal treatments (ECTRs) in BAAs poisoning.
METHODS
We conducted systematic reviews of the literature, screened studies, extracted data, and summarized findings following published EXTRIP methods.
RESULTS
A total of 76 studies (4 in vitro and 2 animal experiments, 1 pharmacokinetic simulation study, 37 pharmacokinetic studies on patients with end-stage kidney disease, and 32 case reports or case series) met inclusion criteria. Toxicokinetic or pharmacokinetic data were available on 334 patients (including 73 for atenolol, 54 for propranolol, and 17 for sotalol). For intermittent hemodialysis, atenolol, nadolol, practolol, and sotalol were assessed as dialyzable; acebutolol, bisoprolol, and metipranolol were assessed as moderately dialyzable; metoprolol and talinolol were considered slightly dialyzable; and betaxolol, carvedilol, labetalol, mepindolol, propranolol, and timolol were considered not dialyzable. Data were available for clinical analysis on 37 BAA poisoned patients (including 9 patients for atenolol, 9 for propranolol, and 9 for sotalol), and no reliable comparison between the ECTR cohort and historical controls treated with standard care alone could be performed. The EXTRIP workgroup recommends against using ECTR for patients severely poisoned with propranolol (strong recommendation, very low quality evidence). The workgroup offered no recommendation for ECTR in patients severely poisoned with atenolol or sotalol because of apparent balance of risks and benefits, except for impaired kidney function in which ECTR is suggested (weak recommendation, very low quality of evidence). Indications for ECTR in patients with impaired kidney function include refractory bradycardia and hypotension for atenolol or sotalol poisoning, and recurrent torsade de pointes for sotalol. Although other BAAs were considered dialyzable, clinical data were too limited to develop recommendations.
CONCLUSIONS
BAAs have different properties affecting their removal by ECTR. The EXTRIP workgroup assessed propranolol as non-dialyzable. Atenolol and sotalol were assessed as dialyzable in patients with kidney impairment, and the workgroup suggests ECTR in patients severely poisoned with these drugs when aforementioned indications are present.
Topics: Adrenergic beta-Antagonists; Consensus; Drug Overdose; Extracorporeal Membrane Oxygenation; Humans
PubMed: 34112223
DOI: 10.1186/s13054-021-03585-7 -
Cureus Sep 2021Long QT syndrome (LQTS) is one of the most common inherited cardiac channelopathies with a prevalence of 1:2000. The condition can be congenital or acquired with 15... (Review)
Review
Long QT syndrome (LQTS) is one of the most common inherited cardiac channelopathies with a prevalence of 1:2000. The condition can be congenital or acquired with 15 recognized genotypes; the most common subtypes are LQTS 1, 2, and 3 making up to 85%-90% of the cases. LQTS is characterized by delayed ventricular cardiomyocyte repolarization manifesting on the surface electrocardiogram (EKG) by a prolonged corrected QT (QTc) interval. The mainstay of treatment for this condition involves in part or combination medical therapy via β-blockers as first-line (or other anti-arrhythmic), left cardiac sympathectomy, or implantable cardiac defibrillator placement. Given the high rate of adverse cardiac events (ACE) or sudden cardiac death (SCD) in this population of patients with this disease, this review seeks to highlight the genotype-specific treatment consensus in β-blocker therapy of the most common subtypes. A database search of PubMed, PMC, and Medline was conducted to ascertain the most recent data in the last five years on the management of LQTS types 1-3 and the role of β-blockers in reducing ACE in these types. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were adhered to in the study selection, and selected studies focused on humans, written in the English Language, and within the last five years of LQTS subtypes 1, 2, and 3. Eleven relevant studies were selected after considering inclusion criteria, exclusion criteria, and quality appraisal within the last five years, focusing on β-blocker selection directed based on the subtypes of LQTS. Two meta-analyses, one cohort study, and eight reviews provided significant data that non-selective β-blockers unequivocally are of benefit in these LQTS types. Summary of findings suggested nadolol followed by propranolol yields the best results in LQTS 1, while nadolol would yield the best effect in LQTS 2 and 3.
PubMed: 34646680
DOI: 10.7759/cureus.17632 -
British Journal of Clinical Pharmacology Aug 2021To investigate the statistical association between hypoglycaemia and β-blocker use and to define what patient and drug characteristics could potentially increase the...
AIMS
To investigate the statistical association between hypoglycaemia and β-blocker use and to define what patient and drug characteristics could potentially increase the risk for its occurrence.
METHODS
We investigated the relationship between pharmacological parameters of β-blockers and the occurrence of hypoglycaemia by conducting a case/non case analysis using the Food and Drug Administration Adverse Event Reporting System database. Pharmacological properties that could represent a predictive factor for hypoglycaemia were analysed through a multilinear binary logistic regression (null hypothesis rejected for values of P < .05). We also performed a systematic review of clinical studies on this association.
RESULTS
Of 83 954 selected reports, 1465 cases (1.75%) of hypoglycaemia were identified. The association was found statistically significant for nadolol (reporting odds ratio [95% confidence interval]: 6.98 [5.40-9.03]), celiprolol (2.35 [1.35-4.10]), propranolol (2.14 [1.87-2.46]) and bisoprolol (1.42 [1.25-1.61]). Paediatric cases (n = 310) showed a positive association with hypoglycaemia for long half-life drugs (odds ratio [95% confidence interval]: 2.232 [1.398-3.563]) and a negative association for β1-selectivity (0.644 [0.414-0.999]). Seven papers were included in the systematic review. Because of great heterogeneity in study design and demographics, hypoglycaemia incidence rates varied greatly among studies, occurring in 1.73% of the cases for propranolol treatment (n total participants = 575), 6.6% for atenolol (n = 30) and 10% for carvedilol (n = 20).
CONCLUSION
Nadolol appears to be the β-blocker significantly most associated with hypoglycaemia and children represent the most susceptible sample. Furthermore, long half-life and nonselective β-blockers seem to increase the risk for its occurrence.
Topics: Adrenergic beta-Antagonists; Carvedilol; Child; Humans; Hypoglycemia; Odds Ratio; Pharmacovigilance
PubMed: 33506522
DOI: 10.1111/bcp.14754 -
Journal of the American Academy of... Oct 2020Flushing and erythema are frequent skin symptoms in rosacea. Because their adequate treatment remains a clinical challenge, new treatment options are explored, such as...
BACKGROUND
Flushing and erythema are frequent skin symptoms in rosacea. Because their adequate treatment remains a clinical challenge, new treatment options are explored, such as oral β-blockers.
OBJECTIVES
To evaluate the efficacy of oral β-blockers for rosacea-associated facial flushing and erythema.
METHODS
PubMed, Embase, Web of Science, and Cochrane Library were systematically searched, including studies providing original data on the efficacy of oral β-blockers in rosacea patients with facial flushing and/or persistent erythema. Risk of bias was assessed using the Cochrane Risk of Bias tool, Newcastle-Ottawa scale, and Quality in Prognosis Studies tool.
RESULTS
Nine studies evaluating the use of carvedilol, propranolol, nadolol, and β-blockers in general were included. Articles studying carvedilol and propranolol showed a large reduction of erythema and flushing during treatment with a rapid onset of symptom control. Bradycardia and hypotension were the most commonly described adverse events.
LIMITATIONS
Most studies had a retrospective design with a small sample size, and outcome measurement was often subjective.
CONCLUSIONS
Oral β-blockers could be an effective treatment option for patients with rosacea with facial erythema and flushing that does not respond to conventional therapy. Larger prospective trials with objective outcome assessment are needed to validate the promising results of these studies.
Topics: Administration, Oral; Adrenergic beta-Antagonists; Bradycardia; Carvedilol; Dermatologic Agents; Drug Evaluation; Erythema; Facial Dermatoses; Flushing; Humans; Hypotension; Nadolol; Propranolol; Retrospective Studies; Rosacea; Treatment Outcome
PubMed: 32360760
DOI: 10.1016/j.jaad.2020.04.129 -
Journal of General Internal Medicine Sep 2013Systematic review of preventive pharmacologic treatments for community-dwelling adults with episodic migraine. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Systematic review of preventive pharmacologic treatments for community-dwelling adults with episodic migraine.
DATA SOURCES
Electronic databases through May 20, 2012.
ELIGIBILITY CRITERIA
English-language randomized controlled trials (RCTs) of preventive drugs compared to placebo or active treatments examining rates of ≥50 % reduction in monthly migraine frequency or improvement in quality of life.
STUDY APPRAISAL AND SYNTHESIS METHODS
We assessed risk of bias and strength of evidence and conducted random effects meta-analyses of absolute risk differences and Bayesian network meta-analysis.
RESULTS
Of 5,244 retrieved references, 215 publications of RCTs provided mostly low-strength evidence because of the risk of bias and imprecision. RCTs examined 59 drugs from 14 drug classes. All approved drugs, including topiramate (9 RCTs), divalproex (3 RCTs), timolol (3 RCTs), and propranolol (4 RCTs); off-label beta blockers metoprolol (4 RCTs), atenolol (1 RCT), nadolol (1 RCT), and acebutolol (1 RCT); angiotensin-converting enzyme inhibitors captopril (1 RCT) and lisinopril (1 RCT); and angiotensin II receptor blocker candesartan (1 RCT), outperformed placebo in reducing monthly migraine frequency by ≥50 % in 200-400 patients per 1,000 treated. Adverse effects leading to treatment discontinuation (68 RCTs) were greater with topiramate, off-label antiepileptics, and antidepressants than with placebo. Limited direct evidence as well as frequentist and exploratory network Bayesian meta-analysis showed no statistically significant differences in benefits between approved drugs. Off-label angiotensin-inhibiting drugs and beta-blockers were most effective and tolerable for episodic migraine prevention.
LIMITATIONS
We did not quantify reporting bias or contact principal investigators regarding unpublished trials.
CONCLUSIONS
Approved drugs prevented episodic migraine frequency by ≥50 % with no statistically significant difference between them. Exploratory network meta-analysis suggested that off-label angiotensin-inhibiting drugs and beta-blockers had favorable benefit-to-harm ratios. Evidence is lacking for long-term effects of drug treatments (i.e., trials of more than 3 months duration), especially for quality of life.
Topics: Adult; Anticonvulsants; Evidence-Based Medicine; Humans; Migraine Disorders; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 23592242
DOI: 10.1007/s11606-013-2433-1 -
The Cochrane Database of Systematic... Sep 2019Randomized controlled trials (RCTs) have yielded conflicting results regarding the ability of beta-blockers to influence perioperative cardiovascular morbidity and...
BACKGROUND
Randomized controlled trials (RCTs) have yielded conflicting results regarding the ability of beta-blockers to influence perioperative cardiovascular morbidity and mortality. Thus routine prescription of these drugs in unselected patients remains a controversial issue. A previous version of this review assessing the effectiveness of perioperative beta-blockers in cardiac and non-cardiac surgery was last published in 2018. The previous review has now been split into two reviews according to type of surgery. This is an update and assesses the evidence in cardiac surgery only.
OBJECTIVES
To assess the effectiveness of perioperatively administered beta-blockers for the prevention of surgery-related mortality and morbidity in adults undergoing cardiac surgery.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, Biosis Previews and Conference Proceedings Citation Index-Science on 28 June 2019. We searched clinical trials registers and grey literature, and conducted backward- and forward-citation searching of relevant articles.
SELECTION CRITERIA
We included RCTs and quasi-randomized studies comparing beta-blockers with a control (placebo or standard care) administered during the perioperative period to adults undergoing cardiac surgery. We excluded studies in which all participants in the standard care control group were given a pharmacological agent that was not given to participants in the intervention group, studies in which all participants in the control group were given a beta-blocker, and studies in which beta-blockers were given with an additional agent (e.g. magnesium). We excluded studies that did not measure or report review outcomes.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, extracted data, and assessed risks of bias. We assessed the certainty of evidence with GRADE.
MAIN RESULTS
We included 63 studies with 7768 participants; six studies were quasi-randomized and the remaining were RCTs. All participants were undergoing cardiac surgery, and in most studies, at least some of the participants were previously taking beta-blockers. Types of beta-blockers were: propranolol, metoprolol, sotalol, esmolol, landiolol, acebutolol, timolol, carvedilol, nadolol, and atenolol. In twelve studies, beta-blockers were titrated according to heart rate or blood pressure. Duration of administration varied between studies, as did the time at which drugs were administered; in nine studies this was before surgery, in 20 studies during surgery, and in the remaining studies beta-blockers were started postoperatively. Overall, we found that most studies did not report sufficient details for us to adequately assess risk of bias. In particular, few studies reported methods used to randomize participants to groups. In some studies, participants in the control group were given beta-blockers as rescue therapy during the study period, and all studies in which the control was standard care were at high risk of performance bias because of the open-label study design. No studies were prospectively registered with clinical trials registers, which limited the assessment of reporting bias. We judged 68% studies to be at high risk of bias in at least one domain.Study authors reported few deaths (7 per 1000 in both the intervention and control groups), and we found low-certainty evidence that beta-blockers may make little or no difference to all-cause mortality at 30 days (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.47 to 1.90; 29 studies, 4099 participants). For myocardial infarctions, we found no evidence of a difference in events (RR 1.05, 95% CI 0.72 to 1.52; 25 studies, 3946 participants; low-certainty evidence). Few study authors reported cerebrovascular events, and the evidence was uncertain (RR 1.37, 95% CI 0.51 to 3.67; 5 studies, 1471 participants; very low-certainty evidence). Based on a control risk of 54 per 1000, we found low-certainty evidence that beta-blockers may reduce episodes of ventricular arrhythmias by 32 episodes per 1000 (RR 0.40, 95% CI 0.25 to 0.63; 12 studies, 2296 participants). For atrial fibrillation or flutter, there may be 163 fewer incidences with beta-blockers, based on a control risk of 327 incidences per 1000 (RR 0.50, 95% CI 0.42 to 0.59; 40 studies, 5650 participants; low-certainty evidence). However, the evidence for bradycardia and hypotension was less certain. We found that beta-blockers may make little or no difference to bradycardia (RR 1.63, 95% CI 0.92 to 2.91; 12 studies, 1640 participants; low-certainty evidence), or hypotension (RR 1.84, 95% CI 0.89 to 3.80; 10 studies, 1538 participants; low-certainty evidence).We used GRADE to downgrade the certainty of evidence. Owing to studies at high risk of bias in at least one domain, we downgraded each outcome for study limitations. Based on effect size calculations in the previous review, we found an insufficient number of participants in all outcomes (except atrial fibrillation) and, for some outcomes, we noted a wide confidence interval; therefore, we also downgraded outcomes owing to imprecision. The evidence for atrial fibrillation and length of hospital stay had a moderate level of statistical heterogeneity which we could not explain, and we, therefore, downgraded these outcomes for inconsistency.
AUTHORS' CONCLUSIONS
We found no evidence of a difference in early all-cause mortality, myocardial infarction, cerebrovascular events, hypotension and bradycardia. However, there may be a reduction in atrial fibrillation and ventricular arrhythmias when beta-blockers are used. A larger sample size is likely to increase the certainty of this evidence. Four studies awaiting classification may alter the conclusions of this review.
Topics: Adrenergic beta-Antagonists; Arrhythmias, Cardiac; Bradycardia; Cardiac Surgical Procedures; Cerebrovascular Disorders; Humans; Hypotension; Morbidity; Myocardial Infarction; Myocardial Ischemia; Perioperative Care; Postoperative Complications; Randomized Controlled Trials as Topic
PubMed: 31544227
DOI: 10.1002/14651858.CD013435 -
The Cochrane Database of Systematic... Sep 2019Randomized controlled trials (RCTs) have yielded conflicting results regarding the ability of beta-blockers to influence perioperative cardiovascular morbidity and...
BACKGROUND
Randomized controlled trials (RCTs) have yielded conflicting results regarding the ability of beta-blockers to influence perioperative cardiovascular morbidity and mortality. Thus routine prescription of these drugs in an unselected population remains a controversial issue. A previous version of this review assessing the effectiveness of perioperative beta-blockers in cardiac and non-cardiac surgery was last published in 2018. The previous review has now been split into two reviews according to type of surgery. This is an update, and assesses the evidence in non-cardiac surgery only.
OBJECTIVES
To assess the effectiveness of perioperatively administered beta-blockers for the prevention of surgery-related mortality and morbidity in adults undergoing non-cardiac surgery.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, Biosis Previews and Conference Proceedings Citation Index-Science on 28 June 2019. We searched clinical trials registers and grey literature, and conducted backward- and forward-citation searching of relevant articles.
SELECTION CRITERIA
We included RCTs and quasi-randomized studies comparing beta-blockers with a control (placebo or standard care) administered during the perioperative period to adults undergoing non-cardiac surgery. If studies included surgery with different types of anaesthesia, we included them if 70% participants, or at least 100 participants, received general anaesthesia. We excluded studies in which all participants in the standard care control group were given a pharmacological agent that was not given to participants in the intervention group, studies in which all participants in the control group were given a beta-blocker, and studies in which beta-blockers were given with an additional agent (e.g. magnesium). We excluded studies that did not measure or report review outcomes.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, extracted data, and assessed risks of bias. We assessed the certainty of evidence with GRADE.
MAIN RESULTS
We included 83 RCTs with 14,967 participants; we found no quasi-randomized studies. All participants were undergoing non-cardiac surgery, and types of surgery ranged from low to high risk. Types of beta-blockers were: propranolol, metoprolol, esmolol, landiolol, nadolol, atenolol, labetalol, oxprenolol, and pindolol. In nine studies, beta-blockers were titrated according to heart rate or blood pressure. Duration of administration varied between studies, as did the time at which drugs were administered; in most studies, it was intraoperatively, but in 18 studies it was before surgery, in six postoperatively, one multi-arm study included groups of different timings, and one study did not report timing of drug administration. Overall, we found that more than half of the studies did not sufficiently report methods used for randomization. All studies in which the control was standard care were at high risk of performance bias because of the open-label study design. Only two studies were prospectively registered with clinical trials registers, which limited the assessment of reporting bias. In six studies, participants in the control group were given beta-blockers as rescue therapy during the study period.The evidence for all-cause mortality at 30 days was uncertain; based on the risk of death in the control group of 25 per 1000, the effect with beta-blockers was between two fewer and 13 more per 1000 (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.89 to 1.54; 16 studies, 11,446 participants; low-certainty evidence). Beta-blockers may reduce the incidence of myocardial infarction by 13 fewer incidences per 1000 (RR 0.72, 95% CI 0.60 to 0.87; 12 studies, 10,520 participants; low-certainty evidence). We found no evidence of a difference in cerebrovascular events (RR 1.65, 95% CI 0.97 to 2.81; 6 studies, 9460 participants; low-certainty evidence), or in ventricular arrhythmias (RR 0.72, 95% CI 0.35 to 1.47; 5 studies, 476 participants; very low-certainty evidence). Beta-blockers may reduce atrial fibrillation or flutter by 26 fewer incidences per 1000 (RR 0.41, 95% CI 0.21 to 0.79; 9 studies, 9080 participants; low-certainty evidence). However, beta-blockers may increase bradycardia by 55 more incidences per 1000 (RR 2.49, 95% CI 1.74 to 3.56; 49 studies, 12,239 participants; low-certainty evidence), and hypotension by 44 more per 1000 (RR 1.40, 95% CI 1.29 to 1.51; 49 studies, 12,304 participants; moderate-certainty evidence).We downgraded the certainty of the evidence owing to study limitations; some studies had high risks of bias, and the effects were sometimes altered when we excluded studies with a standard care control group (including only placebo-controlled trials showed an increase in early mortality and cerebrovascular events with beta-blockers). We also downgraded for inconsistency; one large, well-conducted, international study found a reduction in myocardial infarction, and an increase in cerebrovascular events and all-cause mortality, when beta-blockers were used, but other studies showed no evidence of a difference. We could not explain the reason for the inconsistency in the evidence for ventricular arrhythmias, and we also downgraded this outcome for imprecision because we found few studies with few participants.
AUTHORS' CONCLUSIONS
The evidence for early all-cause mortality with perioperative beta-blockers was uncertain. We found no evidence of a difference in cerebrovascular events or ventricular arrhythmias, and the certainty of the evidence for these outcomes was low and very low. We found low-certainty evidence that beta-blockers may reduce atrial fibrillation and myocardial infarctions. However, beta-blockers may increase bradycardia (low-certainty evidence) and probably increase hypotension (moderate-certainty evidence). Further evidence from large placebo-controlled trials is likely to increase the certainty of these findings, and we recommend the assessment of impact on quality of life. We found 18 studies awaiting classification; inclusion of these studies in future updates may also increase the certainty of the evidence.
Topics: Adrenergic beta-Antagonists; Anesthesia, General; Arrhythmias, Cardiac; Bradycardia; Cause of Death; Humans; Hypotension; Morbidity; Myocardial Infarction; Perioperative Care; Postoperative Complications; Quality of Life; Randomized Controlled Trials as Topic; Surgical Procedures, Operative
PubMed: 31556094
DOI: 10.1002/14651858.CD013438