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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 -
The Cochrane Database of Systematic... Jun 2024Atrial fibrillation (AF) is the most frequent sustained arrhythmia. Cardioversion is a rhythm control strategy to restore normal/sinus rhythm, and can be achieved... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Atrial fibrillation (AF) is the most frequent sustained arrhythmia. Cardioversion is a rhythm control strategy to restore normal/sinus rhythm, and can be achieved through drugs (pharmacological) or a synchronised electric shock (electrical cardioversion).
OBJECTIVES
To assess the efficacy and safety of pharmacological and electrical cardioversion for atrial fibrillation (AF), atrial flutter and atrial tachycardias.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, Conference Proceedings Citation Index-Science (CPCI-S) and three trials registers (ClinicalTrials.gov, WHO ICTRP and ISRCTN) on 14 February 2023.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) at the individual patient level. Patient populations were aged ≥ 18 years with AF of any type and duration, atrial flutter or other sustained related atrial arrhythmias, not occurring as a result of reversible causes.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology to collect data and performed a network meta-analysis using the standard frequentist graph-theoretical approach using the netmeta package in R. We used GRADE to assess the quality of the evidence which we presented in our summary of findings with a judgement on certainty. We calculated differences using risk ratios (RR) and 95% confidence intervals (CI) as well as ranking treatments using a P value. We assessed clinical and statistical heterogeneity and split the networks for the primary outcome and acute procedural success, due to concerns about violating the transitivity assumption.
MAIN RESULTS
We included 112 RCTs (139 records), from which we pooled data from 15,968 patients. The average age ranged from 47 to 72 years and the proportion of male patients ranged from 38% to 92%. Seventy-nine trials were considered to be at high risk of bias for at least one domain, 32 had no high risk of bias domains, but had at least one domain classified as uncertain risk, and one study was considered at low risk for all domains. For paroxysmal AF (35 trials), when compared to placebo, anteroapical (AA)/anteroposterior (AP) biphasic truncated exponential waveform (BTE) cardioversion (RR: 2.42; 95% CI 1.65 to 3.56), quinidine (RR: 2.23; 95% CI 1.49 to 3.34), ibutilide (RR: 2.00; 95% CI 1.28 to 3.12), propafenone (RR: 1.98; 95% CI 1.67 to 2.34), amiodarone (RR: 1.69; 95% CI 1.42 to 2.02), sotalol (RR: 1.58; 95% CI 1.08 to 2.31) and procainamide (RR: 1.49; 95% CI 1.13 to 1.97) likely result in a large increase in maintenance of sinus rhythm until hospital discharge or end of study follow-up (certainty of evidence: moderate). The effect size was larger for AA/AP incremental and was progressively smaller for the subsequent interventions. Despite low certainty of evidence, antazoline may result in a large increase (RR: 28.60; 95% CI 1.77 to 461.30) in this outcome. Similarly, low-certainty evidence suggests a large increase in this outcome for flecainide (RR: 2.17; 95% CI 1.68 to 2.79), vernakalant (RR: 2.13; 95% CI 1.52 to 2.99), and magnesium (RR: 1.73; 95% CI 0.79 to 3.79). For persistent AF (26 trials), one network was created for electrical cardioversion and showed that, when compared to AP BTE incremental energy with patches, AP BTE maximum energy with patches (RR 1.35, 95% CI 1.17 to 1.55) likely results in a large increase, and active compression AP BTE incremental energy with patches (RR: 1.14, 95% CI 1.00 to 1.131) likely results in an increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: high). Use of AP BTE incremental with paddles (RR: 1.03, 95% CI 0.98 to 1.09; certainty of evidence: low) may lead to a slight increase, and AP MDS Incremental paddles (RR: 0.95, 95% CI 0.86 to 1.05; certainty of evidence: low) may lead to a slight decrease in efficacy. On the other hand, AP MDS incremental energy using patches (RR: 0.78, 95% CI 0.70 to 0.87), AA RBW incremental energy with patches (RR: 0.76, 95% CI 0.66 to 0.88), AP RBW incremental energy with patches (RR: 0.76, 95% CI 0.68 to 0.86), AA MDS incremental energy with patches (RR: 0.76, 95% CI 0.67 to 0.86) and AA MDS incremental energy with paddles (RR: 0.68, 95% CI 0.53 to 0.83) probably result in a decrease in this outcome when compared to AP BTE incremental energy with patches (certainty of evidence: moderate). The network for pharmacological cardioversion showed that bepridil (RR: 2.29, 95% CI 1.26 to 4.17) and quindine (RR: 1.53, (95% CI 1.01 to 2.32) probably result in a large increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up when compared to amiodarone (certainty of evidence: moderate). Dofetilide (RR: 0.79, 95% CI 0.56 to 1.44), sotalol (RR: 0.89, 95% CI 0.67 to 1.18), propafenone (RR: 0.79, 95% CI 0.50 to 1.25) and pilsicainide (RR: 0.39, 95% CI 0.02 to 7.01) may result in a reduction in this outcome when compared to amiodarone, but the certainty of evidence is low. For atrial flutter (14 trials), a network could be created only for antiarrhythmic drugs. Using placebo as the common comparator, ibutilide (RR: 21.45, 95% CI 4.41 to 104.37), propafenone (RR: 7.15, 95% CI 1.27 to 40.10), dofetilide (RR: 6.43, 95% CI 1.38 to 29.91), and sotalol (RR: 6.39, 95% CI 1.03 to 39.78) probably result in a large increase in the maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: moderate), and procainamide (RR: 4.29, 95% CI 0.63 to 29.03), flecainide (RR 3.57, 95% CI 0.24 to 52.30) and vernakalant (RR: 1.18, 95% CI 0.05 to 27.37) may result in a large increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: low). All tested electrical cardioversion strategies for atrial flutter had very high efficacy (97.9% to 100%). The rate of mortality (14 deaths) and stroke or systemic embolism (3 events) at 30 days was extremely low. Data on quality of life were scarce and of uncertain clinical significance. No information was available regarding heart failure readmissions. Data on duration of hospitalisation was scarce, of low quality, and could not be pooled.
AUTHORS' CONCLUSIONS
Despite the low quality of evidence, this systematic review provides important information on electrical and pharmacological strategies to help patients and physicians deal with AF and atrial flutter. In the assessment of the patient comorbidity profile, antiarrhythmic drug onset of action and side effect profile versus the need for a physician with experience in sedation, or anaesthetics support for electrical cardioversion are key aspects when choosing the cardioversion method.
Topics: Aged; Humans; Middle Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Bias; Electric Countershock; Network Meta-Analysis; Randomized Controlled Trials as Topic; Tachycardia; Male; Female
PubMed: 38828867
DOI: 10.1002/14651858.CD013255.pub2 -
Emergency Medicine Journal : EMJ Feb 2015We performed a systematic review of the literature to compare the efficacy of different drug therapies for the termination of stable, monomorphic ventricular tachycardia... (Review)
Review
OBJECTIVE
We performed a systematic review of the literature to compare the efficacy of different drug therapies for the termination of stable, monomorphic ventricular tachycardia (VT).
METHODS
We searched EMBASE, MEDLINE and Cochrane for trials from 1965 through July 2013 using a search strategy derived from the following clinical question in PICO format:
PATIENTS
Adults (≥18 years) with stable monomorphic VT;
INTERVENTION
Intravenous antidysrhythmic drug; Comparator: Intravenous lidocaine or amiodarone;
OUTCOME
Termination of VT. For all drug comparisons, we calculated relative risks (RR; 95% CI) and number needed to treat (NNT, 95% CI) between drugs. We also evaluated the methodological quality of the studies.
RESULTS
Our search yielded 219 articles by PubMed and 390 articles by EMBASE. 3 prospective studies (n=93 patients) and 2 retrospective studies (n=173 patients) met our inclusion and exclusion criteria. From the prospective studies, RR of VT termination of procainamide versus lidocaine was 3.7 (1.3-10.5); ajmaline versus lidocaine, RR=5.3 (1.4-20.5); and sotalol versus lidocaine, RR=3.9 (1.3-11.5). From the retrospective studies: procainamide versus lidocaine, RR=2.2 (1.2-4.0); and procainamide versus amiodarone RR=4.3 (0.8-23.6). All 5 reviewed studies had quality issues, including potential bias for randomisation and concealment.
CONCLUSIONS
Based on limited available evidence from small heterogeneous human studies, for the treatment of stable, monomorphic VT, procainamide, ajmaline and sotalol were all superior to lidocaine; amiodarone was not more effective than procainamide.
Topics: Administration, Intravenous; Anti-Arrhythmia Agents; Humans; Prospective Studies; Retrospective Studies; Tachycardia, Ventricular
PubMed: 24042252
DOI: 10.1136/emermed-2013-202973 -
Clinical Cardiology Oct 2019Brugada syndrome (BrS) is associated with sudden cardiac death (SCD). Although implantable cardioverter-defibrillator (ICD) implantation is recommended, the long-term...
BACKGROUND
Brugada syndrome (BrS) is associated with sudden cardiac death (SCD). Although implantable cardioverter-defibrillator (ICD) implantation is recommended, the long-term outcomes and follow-up data with regard to ICD complications have led to controversy.
HYPOTHESIS
In the present study, we described the data assimilated in a total of 11 studies, analyzing the outcome in 747 BrS patients receiving ICD.
METHODS
Data were performed and analyzed after a systematic review of literature compiled from a thorough database search (PubMed, Web of Science, Cochrane Library, and Cinahl).
RESULTS
The mean age of patients receiving ICD was (43.1 ± 13.4, 82.5% males, 46.6% spontaneous BrS type I). Around 15.3% of the patients were admitted due to SCD and 10.4% suffered from atrial arrhythmia. Appropriate shocks were documented in 18.1% of the patients over a mean follow-up period of 82.3 months (47.5-110.4). The following complications were recorded: lead failure and fracture (5.4%), lead perforation (0.7%), lead dislodgement (1.7%), infection (3.9%), pain (0.4%), subclavian vein thrombosis (0.3%), pericardial effusion (0.1%), endocarditis (0.1%), psychiatric problems (1.5%), pneumothorax (0.7%). Inappropriate shocks were documented in 18.1% of the patients. The management of inappropriate shocks was achieved by pulmonary vein isolation (0.5%), drug treatment with sotalol (1.3%) or sotalol with beta-blocker (0.3%) and hydroquinidine (0.1%).
CONCLUSIONS
ICD therapy in BrS is associated with relevant ICD-related complications including a substantial risk of inappropriate shocks more frequently in symptomatic BrS patients.
Topics: Humans; Brugada Syndrome; Death, Sudden, Cardiac; Defibrillators, Implantable; Electrocardiography; Follow-Up Studies; Global Health; Survival Rate; Time Factors
PubMed: 31441080
DOI: 10.1002/clc.23247 -
PharmacoEconomics Aug 2023Atrial fibrillation (AF) remains the most common form of cardiac arrhythmia. Management of AF aims to reduce the risk of stroke, heart failure and premature mortality...
BACKGROUND
Atrial fibrillation (AF) remains the most common form of cardiac arrhythmia. Management of AF aims to reduce the risk of stroke, heart failure and premature mortality via rate or rhythm control. This study aimed to review the literature on the cost effectiveness of treatment strategies to manage AF among adults living in low-, middle- and high-income countries.
METHODS
We searched MEDLINE (OvidSp), Embase, Web of Science, Cochrane Library, EconLit and Google Scholar for relevant studies between September 2022 and November 2022. The search strategy involved medical subject headings or related text words. Data management and selection was performed using EndNote library. The titles and abstracts were screened followed by eligibility assessment of full texts. Selection, assessment of the risk of bias within the studies, and data extraction were conducted by two independent reviewers. The cost-effectiveness results were synthesised narratively. The analysis was performed using Microsoft Excel 365. The incremental cost effectiveness ratio for each study was adjusted to 2021 USD values.
RESULTS
Fifty studies were included in the analysis after selection and risk of bias assessment. In high-income countries, apixaban was predominantly cost effective for stroke prevention in patients at low and moderate risk of stroke, while left atrial appendage closure (LAAC) was cost effective in patients at high risk of stroke. Propranolol was the cost-effective choice for rate control, while catheter ablation and the convergent procedure were cost-effective strategies in patients with paroxysmal and persistent AF, respectively. Among the anti-arrhythmic drugs, sotalol was the cost-effective strategy for rhythm control. In middle-income countries, apixaban was the cost-effective choice for stroke prevention in patients at low and moderate risk of stroke while high-dose edoxaban was cost effective in patients at high risk of stroke. Radiofrequency catheter ablation was the cost-effective option in rhythm control. No data were available for low-income countries.
CONCLUSION
This systematic review has shown that there are several cost-effective strategies to manage AF in different resource settings. However, the decision to use any strategy should be guided by objective clinical and economic evidence supported by sound clinical judgement.
REGISTRATION
CRD42022360590.
Topics: Adult; Humans; Atrial Fibrillation; Cost-Effectiveness Analysis; Developed Countries; Cost-Benefit Analysis; Stroke
PubMed: 37204698
DOI: 10.1007/s40273-023-01276-5 -
Frontiers in Cardiovascular Medicine 2022Whether early pharmacologic cardioversion is necessary for recent-onset atrial fibrillation is still controversial. Current meta-analyses were limited to evaluating the...
Effect of Early Pharmacologic Cardioversion vs. Non-early Cardioversion in the Patients With Recent-Onset Atrial Fibrillation Within 4-Week Follow-Up Period: A Systematic Review and Network Meta-Analysis.
BACKGROUND
Whether early pharmacologic cardioversion is necessary for recent-onset atrial fibrillation is still controversial. Current meta-analyses were limited to evaluating the effects within 24 h without sufficient considering longer follow-up outcomes. We aimed to compare the effect of early pharmacologic cardioversion and non-early cardioversion in patients with recent-onset atrial fibrillation within 4-weeks of follow-up.
METHODS
We searched the Cochrane Library, EMBASE, MEDLINE, PubMed, Web of Science, ClinicalTrials.gov, and Clinicaltrialsregister. eu for randomized controlled trials (RCTs) published before November 2021 comparing early pharmacologic cardioversion and non-early cardioversion in recent-onset atrial fibrillation and synthesized data in accordance with PRISMA-Systematic Reviews and Network Meta-Analysis (NMA). Early pharmacological cardioversion referred to immediate cardioversion with antiarrhythmic drugs (i.e., amiodarone, propafenone, flecainide, tedisamil, vernakalant, vanoxerine, and sotalol) upon admission, while non-early cardioversion involved the administration of rate-control or placebo medication without immediate cardioversion.
RESULTS
16 RCTs with 2,395 patients were included. Compared to non-early cardioversion, a systematic review showed that early pharmacologic cardioversion resulted in a higher probability of sinus rhythm maintenance within 24 h (odds ratios [OR] 2.50, 95% credible interval [CrI] 1.76 to 3.54) and 1-week (2.50, 1.76 to 3.54), however, there was no significant difference in sinus rhythm maintenance within 4-weeks (1.37, 0.90 to 2.09). In subgroup analysis, the Bayesian NMA revealed that vernakalant may be successful in sinus rhythm maintenance within both 24 h (3.55, 2.28 to 5.55) and 1-week (2.72, 1.72 to 4.31). The results were consistent with the frequentist NMA.
CONCLUSIONS
Non-early pharmacologic cardioversion may not be inferior to early cardioversion within a 4-week follow-up period in patients with recent-onset atrial fibrillation. The evidence remains insufficient to determine which antiarrhythmic agent is optimal in the longer run. Further high-quality relevant RCTs are necessary.
CLINICAL TRIAL REGISTRATION
PROSPERO CRD42020166862.
PubMed: 35479281
DOI: 10.3389/fcvm.2022.843939 -
Circulation. Arrhythmia and... Nov 2019In patients with an implantable cardioverter-defibrillator (ICD), shocks are associated with increased morbidity and mortality. Therefore, we conducted this study to... (Meta-Analysis)
Meta-Analysis
Antiarrhythmic Drugs or Catheter Ablation in the Management of Ventricular Tachyarrhythmias in Patients With Implantable Cardioverter-Defibrillators: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
BACKGROUND
In patients with an implantable cardioverter-defibrillator (ICD), shocks are associated with increased morbidity and mortality. Therefore, we conducted this study to evaluate the efficacy and safety of antiarrhythmic drugs and catheter ablation (CA) in the treatment of ventricular tachyarrhythmias (VT) in patients with an ICD.
METHODS
An electronic database search for randomized controlled trials that evaluated antiarrhythmic drugs and CA in patients with ICD was conducted. The primary outcome was recurrent VT. Secondary outcomes were ICD shocks and any deaths. Bayesian and frequentist network meta-analyses were performed to calculate hazard ratios (HRs) and 95% credible intervals (CrIs)/CIs.
RESULTS
Twenty-two randomized controlled trials were identified (3828 total patients; age 64.3±11.4; 79% males). The use of amiodarone was associated with a significantly reduced rate of VT recurrence compared with control (HR=0.34 [95% CrI=0.15-0.74]; absolute risk difference=-0.23 [95% CrI=-0.23 to -0.09]; number needed to treat=4). Sotalol was associated with increased risk of VT recurrence compared with amiodarone (HR=2.88 [95% CrI=1.35-6.46]). Compared with control, amiodarone (HR=0.33 [95% CrI=0.15-0.76]; absolute risk difference=-0.17 [95% CrI=-0.32 to -0.06]; number needed to treat=6) and CA (HR=0.52 [95% CrI=0.30-0.89; absolute risk difference=-0.12 [95% CrI=-0.24 to -0.03]; number needed to treat=8) were associated with significantly reduced ICD shocks. Compared with amiodarone, sotalol was associated with significantly increased ICD shocks (HR=2.70 [95% CrI=1.17-6.71]). The rate of death was not significantly different between the competing strategies. The node-splitting method showed no inconsistency.
CONCLUSIONS
Among patients with an ICD, amiodarone significantly reduced VT recurrence and ICD shocks, while CA reduced ICD shocks. Sotalol significantly increased VT recurrence and ICD shocks compared with amiodarone. The long-term side effects of amiodarone and early complications of CA should be weighed carefully according to specific patient characteristics.
Topics: Anti-Arrhythmia Agents; Catheter Ablation; Defibrillators, Implantable; Disease Management; Humans; Randomized Controlled Trials as Topic; Tachycardia, Ventricular; Treatment Outcome
PubMed: 31698933
DOI: 10.1161/CIRCEP.119.007600 -
BMJ Open Oct 2020Postoperative atrial fibrillation (POAF) is a potentially lethal and morbid complication after open heart surgery. This systematic review and meta-analysis aimed to... (Meta-Analysis)
Meta-Analysis
PURPOSE
Postoperative atrial fibrillation (POAF) is a potentially lethal and morbid complication after open heart surgery. This systematic review and meta-analysis aimed to investigate metoprolol compared with other treatments for prophylaxis against POAF.
METHODS
We searched CENTRAL, MEDLINE, EMBASE and trial registries for randomised controlled trials that evaluated metoprolol for preventing the occurrence of POAF after surgery against other treatments or placebo. Random-effects model was used for estimating the risk ratios (RRs) and mean differences with 95% CIs.
RESULTS
Nine trials involving 1570 patients showed metoprolol reduced POAF compared with placebo (416 patients; RR 0.46, 95% CI 0.33 to 0.66; I²=21%; risk difference (RD) -0.19, 95% CI -0.28 to -0.10). However, metoprolol increased the risk of POAF compared with carvedilol (159 patients; RR 1.59, 95% CI 1.20 to 2.12; I²=4%; RD 0.13, 95% CI 0.06 to 0.20). There was no difference when compared with sotalol or amiodarone. The occurrence of cardiovascular conditions after drugs administration or death between the groups was not different. The overall quality of evidence was moderate to high. Subgroup analysis and funnel plot were not performed.
CONCLUSIONS
Metoprolol is effective in preventing POAF compared with placebo and showed no difference with class III antiarrhythmic drugs. Death and thromboembolism are associated with open heart surgery, but not significant in relation to the use of metoprolol.
PROSPERO REGISTRATION NUMBER
CRD42019131585.
Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiac Surgical Procedures; Humans; Metoprolol; Postoperative Complications
PubMed: 33130564
DOI: 10.1136/bmjopen-2020-038364 -
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