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World Journal For Pediatric &... May 2017Paradoxical hypertension after repair of coarctation of the aorta is a well-known phenomenon. The pathogenesis involves the activation of the sympathetic nervous system... (Review)
Review
BACKGROUND
Paradoxical hypertension after repair of coarctation of the aorta is a well-known phenomenon. The pathogenesis involves the activation of the sympathetic nervous system (first phase) and renin-angiotensin system (second phase). Only a limited number of different treatment strategies have been published in the literature, without any comparative studies.
METHODS
Our aim was to describe the current international practice variation surrounding pharmacological treatment currently being employed to treat paradoxical hypertension following the repair of coarctation of the aorta in children. We performed an online survey among 197 members of the Pediatric Cardiac Intensive Care Society. We also conducted a systematic review of the literature regarding the treatment of paradoxical hypertension.
RESULTS
Eighty-eight people (45%), from 62 different centers, responded and answered the questions regarding blood pressure control. Nitroprusside is the first drug of choice for initial blood pressure control in 66% of respondents, esmolol in 11%, labetalol in 11%, and angiotensin-converting enzyme inhibitors (ACEIs) are used by 3% of respondents. For oral blood pressure control after discharge from the pediatric intensive care unit, 75% of respondents use ACEIs, 18% use labetalol, and 12% use other beta-blockers (propranolol, carvedilol, atenolol, metoprolol). The systematic review identified 14 articles reporting pharmacological treatment of direct postoperative hypertension following coarctation repair.
CONCLUSION
There is wide practice variability, due to the lack of sufficient compelling evidence. The majority (66%) of caregivers use nitroprusside to control blood pressure in the acute postoperative phase. The ACEIs are the drug of choice for chronic blood pressure control.
Topics: Antihypertensive Agents; Aortic Coarctation; Blood Pressure; Child; Humans; Hypertension; Postoperative Complications; Practice Guidelines as Topic
PubMed: 28520538
DOI: 10.1177/2150135117690104 -
International Journal of Health Sciences 2019Uncontrolled hypertension is a main predisposing risk factor leading to chronic atrial fibrillation (AF). Although several treatment methods for patients with HTN and AF... (Review)
Review
OBJECTIVES
Uncontrolled hypertension is a main predisposing risk factor leading to chronic atrial fibrillation (AF). Although several treatment methods for patients with HTN and AF were developed in past decades, further investigations of their efficacies are needed. This systematic narrative review presents an overview of studies reporting treatment efficacies in patients with HTN and/or AF.
METHODS
A narrative-based systematic review was performed using EMBASE, Medline, PubMed, Google Scholar, and the Cochrane Library searching for relevant papers published between October 2008 and October 2018. Out of 4481 studies, only 15 studies could be included following the inclusion criteria.
RESULTS
Included studies reported treatment measures, measured outcomes, and efficacies in adult patients with HTN and AF with defined interventions and methodologies. Treatment methods with effective outcomes were administration of hydrochlorothiazide, losartan or atenolol, telmisartan or amlodipine, or general anti-hypertensive drugs. Treatment methods that showed the most effective outcomes (lowering AF recurrence and improving BP control) were those containing pulmonary vein (or antrum) isolation (PVI/PVAI) (6 studies) and/or in conjunction with renal denervation (RDN)(6 studies). Treatment methods showing the most effective outcomes were PVI/PVAI in conjunction with RDN.
CONCLUSION
The latest evidence shows that PVI (in conjunction with RDN in some instances) was more efficacious among patients suffering from HTN and/or AF.
PubMed: 31745397
DOI: No ID Found -
Frontiers in Neuroscience 2018Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and has minimal risk for extrapyramidal symptoms. Therapeutic benefits, however, are...
Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and has minimal risk for extrapyramidal symptoms. Therapeutic benefits, however, are accompanied by a myriad of cardiometabolic side-effects. The specific reasons for clozapine's high propensity to cause adverse cardiometabolic events remain unknown, but it is believed that autonomic dysfunction may play a role in many of these. This systematic review summarizes the literature on autonomic dysfunction and related cardiovascular side effects associated with clozapine treatment. A search of the EMBASE, MEDLINE, and EBM Cochrane databases was conducted using the search terms antipsychotic agents, antipsychotic drug, antipsychotic, schizophrenia, schizophren, psychos, psychotic, mental ill, mental disorder, neuroleptic, cardiovascular, cardiovascular diseases, clozapine, clozaril, autonomic, sympathetic, catecholamine, norepinephrine, noradrenaline, epinephrine, adrenaline. The search yielded 37 studies that were reviewed, of which only 16 studies have used interventions to manage cardiovascular side effects. Side effects reported in the studies include myocarditis, orthostatic hypotension and tachycardia. These were attributed to sympathetic hyperactivity, decreased vagal contribution, blockade of cholinergic and adrenergic receptors, reduced heart rate variability and elevated catecholamines with clozapine use. Autonomic neuropathy was identified by monitoring blood pressure and heart rate changes in response to stimuli and by spectral analysis of heart rate variability. Metoprolol, lorazepam, atenolol, propranolol, amlodipine, vasopressin and norepinephrine infusion were used to treat tachycardia and fluctuations in blood pressure, yet results were limited to case reports. The results indicate there is a lack of clinical studies investigating autonomic dysfunction and a limited use of interventions to manage cardiovascular side effects associated with clozapine. As there is often no alternative treatment for refractory schizophrenia, the current review highlights the need for better designed studies, use of autonomic tests for prevention of cardiovascular disease and development of novel interventions for clozapine-induced side effects.
PubMed: 29670504
DOI: 10.3389/fnins.2018.00203 -
Emergency Medicine Journal : EMJ Sep 2018Beta blockers (β-blockers) remain a standard therapy in the early treatment of acute coronary syndromes. However, β-blocker therapy in patients with cocaine-associated... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Beta blockers (β-blockers) remain a standard therapy in the early treatment of acute coronary syndromes. However, β-blocker therapy in patients with cocaine-associated chest pain (CACP) continues to be an area of debate due to the potential risk of unopposed α-adrenergic stimulation and coronary vasospasm. Therefore, we performed a systematic review and meta-analysis of available studies to compare outcomes of β-blocker versus no β-blocker use among patients with CACP.
METHODS
We searched the MEDLINE and EMBASE databases through September 2016 using the keywords 'beta blocker', 'cocaine' and commonly used β-blockers ('atenolol', 'bisoprolol', 'carvedilol', 'esmolol', 'metoprolol' and 'propranolol') to identify studies evaluating β-blocker use among patients with CACP. We specifically focused on studies comparing outcomes between β-blocker versus no β-blocker usage in patients with CACP. Studies without a comparison between β-blocker and no β-blocker use were excluded. Outcomes of interest included non-fatal myocardial infarction (MI) and all-cause mortality. Quantitative data synthesis was performed using a random-effects model and heterogeneity was assessed using Q and Istatistics.
RESULTS
A total of five studies evaluating 1794 subjects were included. Overall, there was no significant difference on MI in patients with CACP on β-blocker versus no β-blocker (OR 1.36, 95% CI 0.68 to 2.75; p=0.39). Similarly, there was no significant difference in all-cause mortality in patients on β-blocker versus no β-blocker (OR 0.68, 95% CI 0.26 to 1.79; p=0.43).
CONCLUSIONS
In patients presenting with acute chest pain and underlying cocaine, β-blocker use does not appear to be associated with an increased risk of MI or all-cause mortality.
Topics: Humans; Acute Coronary Syndrome; Adrenergic beta-Antagonists; Atenolol; Bisoprolol; Carvedilol; Cocaine; Metoprolol; Propanolamines; Propranolol
PubMed: 29921621
DOI: 10.1136/emermed-2017-207065 -
Lancet (London, England) Mar 2017Globally, most patients with hypertension are treated with monotherapy, and control rates are poor because monotherapy only reduces blood pressure by around 9/5 mm Hg on... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Globally, most patients with hypertension are treated with monotherapy, and control rates are poor because monotherapy only reduces blood pressure by around 9/5 mm Hg on average. There is a pressing need for blood pressure-control strategies with improved efficacy and tolerability. We aimed to assess whether ultra-low-dose combination therapy could meet these needs.
METHODS
We did a randomised, placebo-controlled, double-blind, crossover trial of a quadpill-a single capsule containing four blood pressure-lowering drugs each at quarter-dose (irbesartan 37·5 mg, amlodipine 1·25 mg, hydrochlorothiazide 6·25 mg, and atenolol 12·5 mg). Participants with untreated hypertension were enrolled from four centres in the community of western Sydney, NSW, Australia, mainly by general practitioners. Participants were randomly allocated by computer to either the quadpill or matching placebo for 4 weeks; this treatment was followed by a 2-week washout, then the other study treatment was administered for 4 weeks. Study staff and participants were unaware of treatment allocations, and masking was achieved by use of identical opaque capsules. The primary outcome was placebo-corrected 24-h systolic ambulatory blood pressure reduction after 4 weeks and analysis was by intention to treat. We also did a systematic review of trials evaluating the efficacy and safety of quarter-standard-dose blood pressure-lowering therapy against placebo. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12614001057673. The trial ended after 1 year and this report presents the final analysis.
FINDINGS
Between November, 2014, and December, 2015, 55 patients were screened for our randomised trial, of whom 21 underwent randomisation. Mean age of participants was 58 years (SD 11) and mean baseline office and 24-h systolic and diastolic blood pressure levels were 154 (14)/90 (11) mm Hg and 140 (9)/87 (8) mm Hg, respectively. One individual declined participation after randomisation and two patients dropped out for administrative reasons. The placebo-corrected reduction in systolic 24-h blood pressure with the quadpill was 19 mm Hg (95% CI 14-23), and office blood pressure was reduced by 22/13 mm Hg (p<0·0001). During quadpill treatment, 18 (100%) of 18 participants achieved office blood pressure less than 140/90 mm Hg, compared with six (33%) of 18 during placebo treatment (p=0·0013). There were no serious adverse events and all patients reported that the quadpill was easy to swallow. Our systematic review identified 36 trials (n=4721 participants) of one drug at quarter-dose and six trials (n=312) of two drugs at quarter-dose, against placebo. The pooled placebo-corrected blood pressure-lowering effects were 5/2 mm Hg and 7/5 mm Hg, respectively (both p<0·0001), and there were no side-effects from either regimen.
INTERPRETATION
The findings of our small trial in the context of previous randomised evidence suggest that the benefits of quarter-dose therapy could be additive across classes and might confer a clinically important reduction in blood pressure. Further examination of the quadpill concept is needed to investigate effectiveness against usual treatment options and longer term tolerability.
FUNDING
National Heart Foundation, Australia; University of Sydney; and National Health and Medical Research Council of Australia.
Topics: Female; Humans; Male; Middle Aged; Administration, Oral; Amlodipine; Antihypertensive Agents; Atenolol; Biphenyl Compounds; Blood Pressure; Cross-Over Studies; Double-Blind Method; Drug Combinations; Hydrochlorothiazide; Hypertension; Irbesartan; Medication Adherence; Tetrazoles; Treatment Outcome
PubMed: 28190578
DOI: 10.1016/S0140-6736(17)30260-X -
American Journal of Cardiovascular... Mar 2021Cardiovascular diseases are the main cause of mortality worldwide, and systemic arterial hypertension is associated with a large number of these cases. The objective of... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Cardiovascular diseases are the main cause of mortality worldwide, and systemic arterial hypertension is associated with a large number of these cases. The objective of health professionals and health policies should be searching for the best therapeutics to control this disease. A recent consensus indicated that β-blockers have recently lost their place in initial indications for the treatment of systemic arterial hypertension and are now more indicated for the treatment of hypertension in association with other clinical situations such as angina, heart failure and arrhythmia; however, it is known that this approach was based on studies that evaluated older β-blockers such as atenolol.
OBJECTIVE
The main objective of this study was to perform a systematic review with subsequent meta-analysis on the use of nebivolol for hypertensive disease treatment, comparing it with drugs of the main antihypertensive classes.
METHODS
This systematic review was based on a search of the MEDLINE (via Pubmed), Scopus, Cochrane, International Pharmaceuticals Abstracts (IPA), and Lilacs databases for randomized and double-blind clinical trials. In addition, we also searched for gray literature studies, to 31 July 2015. Next, a cumulative meta-analysis was performed, with studies being added in a sequential manner, evaluating their impact on the combined effect. For this project, we only meta-analyzed direct comparisons of random effect.
RESULTS
Overall, 981 clinical trials were included in this systematic review. After careful analysis, 34 randomized and double-blind clinical trials were included to investigate the efficacy of nebivolol on systolic (SBP) and diastolic blood pressure (DBP) control and adverse effects. The study population comprised 12,465 patients with systemic arterial hypertension (SAH) aged between 18 and 85 years; 17% of subjects were of Black ethnicity, approximately 55% were men, and almost 10% had diabetes. In SBP management, nebivolol was superior to other β-blockers and diuretics and showed no difference in efficacy when compared with angiotensin receptor blockers or calcium channel blockers. There were insufficient studies on angiotensin-converting enzyme inhibitors for adequate comparison of both SBP and DBP control. For DBP control, nebivolol was more efficient than other β-blockers, angiotensin receptor blockers, diuretics, and calcium channel blockers.
DISCUSSION
Nebivolol is a third-generation β-blocker with additional capabilities to improve blood pressure levels in patients with arterial hypertension, because it acts by additional mechanisms such as endothelium-dependent vasodilation associated with L-arginine and oxide nitric acid, nitric oxide activity on smooth muscle cells, decreasing platelet aggregation, and leukocyte adhesion in the endothelium, decreasing oxidative stress. Although nebivolol has shown good results in controlling hypertension in this study (with few adverse events when compared with placebo treatment) and has an unquestionable benefit in individuals with heart failure (mainly with reduced ejection fraction), there is a lack of studies proving the benefit of this drug for controlling hypertension and reducing clinical outcomes such as cardiovascular (or general) mortality, acute myocardial infarction, or stroke.
CONCLUSIONS
Nebivolol demonstrated at least similar control of blood pressure levels in hypertensive individuals when compared with drugs of the most used classes. In addition, in relation to the control of arterial hypertension, studies with clinical outcomes should be performed to ensure the use of this drug in detriment to others with these well-established results.
Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Age Factors; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Diabetes Mellitus; Diuretics; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged; Multicenter Studies as Topic; Nebivolol; Randomized Controlled Trials as Topic; Sex Factors; Socioeconomic Factors; Young Adult
PubMed: 32710438
DOI: 10.1007/s40256-020-00422-0 -
Hypertension Research : Official... Apr 2019Although beta blockers have been used as initial therapy for ischemic heart diseases and heart failure, the beneficial effects of beta blockers are controversial...
Although beta blockers have been used as initial therapy for ischemic heart diseases and heart failure, the beneficial effects of beta blockers are controversial compared with other antihypertensive agents as initial therapy for hypertension without compelling indications. Moreover, atenolol has been most commonly used with beta blockers. The objective of the present systematic review associated with the Japanese Society of Hypertension (JSH) 2019 Hypertension Guideline (Clinical Question 6) was to assess the outcomes (cardiocerebrovascular mortality, total cause mortality, hypotension, bradycardia, other adverse effects, and changes in systolic blood pressure (SBP)) of currently used carvedilol and bisoprolol as initial therapy for adult hypertension without compelling indications. Two independent systematic reviewers searched randomized controlled trials (RCTs) up to October 2017 in the Cochrane Hypertension Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, EMBASE Ovid, and ClinicalTrials.gov. Finally, eight RCTs with 2494 participants were identified to meet our inclusion criteria. There were no RCTs in which cardiocerebrovascular mortality, total cause mortality, hypotension, and bradycardia were assessed between carvedilol or bisoprolol and placebo. SBP-lowering effects were significantly increased for bisoprolol compared with placebo. Here, 50 mg carvedilol significantly reduced SBP compared with placebo, whereas 12.5 mg or 25 mg did not. Regarding adverse effects, no differences were noted between carvedilol and placebo (two RCTs, 286 participants, moderate certainly evidence). In conclusion, current evidence does not support carvedilol or bisoprolol as first-line therapy for adult hypertension without compelling indications.
Topics: Antihypertensive Agents; Bisoprolol; Blood Pressure; Carvedilol; Humans; Hypertension; Treatment Outcome
PubMed: 30948819
DOI: 10.1038/s41440-018-0174-6 -
American Journal of Cardiovascular... Oct 2020Obesity hypertension is an ongoing pandemic. The first-line medications to treat this condition are still subject to debate. We compared diuretics, calcium-channel... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Obesity hypertension is an ongoing pandemic. The first-line medications to treat this condition are still subject to debate. We compared diuretics, calcium-channel blockers (CCB), beta-blockers (BB), angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) as an initial antihypertensive therapy for prevention of cardiovascular morbimortality of hypertensive individuals who are overweight or obese.
METHODS
We conducted a search of the literature for randomized clinical trials in which at least 50% of the participants were overweight or obese. The primary outcomes were all-cause mortality, cardiovascular mortality, acute myocardial infarction (MI), heart failure (HF), stroke, or end-stage renal disease.
RESULTS
Our search yielded 16 randomized studies. Comparisons of two classes of drugs with at least two studies indicated that (1) CCB and ACEI increased the risk of HF [relative risk (RR) = 2.26; 95% confidence interval (CI) 1.16-4.40] and stroke [hazard ratio (HR) = 1.13; 1.00-1.26]), respectively, compared to diuretics; and (2) CCB showed a reduction in stroke (HR = 0.77; 0.66-0.89) and total mortality (HR = 0.94; 0.87-1.01) compared to the BB atenolol. Comparisons of two classes of antihypertensive medications with only one study showed that the risk of MI was higher with ARB valsartan versus CCB (HR = 1.19; 95% CI 1.02-1.38, p = 0.02). In contrast, losartan lowered the risk of a composite cardiovascular outcome compared to atenolol (HR = 0.87; 95% CI 0.77-0.98, p = 0.02).
CONCLUSIONS
In hypertensive subjects with excess weight, diuretics are more effective for preventing HF and stroke than CCB and ACEI, respectively. CCB are a good first-line choice for prevention of cardiovascular disease, except HF.
Topics: Antihypertensive Agents; Cardiometabolic Risk Factors; Cardiovascular Diseases; Humans; Hypertension; Obesity; Randomized Controlled Trials as Topic
PubMed: 31898196
DOI: 10.1007/s40256-019-00393-x -
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 -
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