scholarly journals Efficacy and safety of intravenous beta-blockers in acute atrial fibrillation and flutter is dependent on beta-1 selectivity: a systematic review and meta-analysis of randomised trials

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M Perrett ◽  
N Gohil ◽  
O Tica ◽  
K.V Bunting ◽  
D Kotecha
Keyword(s):  
Atrial Fibrillation ◽  
Systematic Review ◽  
Heart Rate ◽  
Adverse Events ◽  
Sinus Rhythm ◽  
Beta Blockers ◽  
Meta Analysis ◽  
Efficacy And Safety ◽  
Target Heart Rate ◽  
Significant Difference

Abstract Background Intravenous (IV) beta-blockers are commonly used to manage patients with acute atrial fibrillation (AF) and atrial flutter (AFl). Important pharmacodynamic differences exist amongst beta-blockers, and the choice of beta-blocker or other therapy is often not evidence-based. Purpose Systematic review and meta-analysis of randomised controlled trials (RCTs) in the setting of acute AF/AFl to assess the efficacy and safety of IV beta-blockers against other pharmacological interventions (diltiazem, verapamil, digoxin, anti-arrhythmic drugs or placebo). Methods Prospectively registered (PROSPERO: CRD42020204772). MEDLINE, EMBASE and Cochrane Register were searched from inception to August 2020. The primary outcomes were reduction in heart rate and proportion of patients achieving study-defined target heart rate. Secondary outcomes included conversion to sinus rhythm and incidence of adverse events. Beta-blockers were divided according to beta-1 adrenoreceptor selectivity. Meta-analysis was performed to calculate risk ratios (RR) and standardised mean differences (SMD) using random-effects, and fixed-effects within beta-1 subgroups. Results From 5974 studies, 12 RCTs were included with variable risk of bias, encompassing 1152 participants with mean age 62 years, 38% women and baseline heart rate 137 beats/minute. With high heterogeneity (I2=87%; p<0.001), there was no difference in the reduction in heart rate between beta-blockers and comparators (SMD −0.65, 95% CI −1.63–0.21; p=0.19), and no difference in the proportion that achieved target heart rate (RR 0.85, 95% CI 0.36–1.97; p=0.70). Analysis by beta-1 selectivity demonstrated that conventional beta-1 blockers (metoprolol, esmolol) were inferior for target heart rate reduction (RR 0.33, 95% CI 0.17–0.64; p=0.001), whereas super-selective agents (landiolol) were superior (RR 1.98, 95% CI 1.54–2.54; p<0.001). There was no difference in the rate of conversion to sinus rhythm between beta-blockers and comparators (RR 1.15, 95% CI 0.92–1.44; p=0.21). Adverse events were similar in both groups overall, with no significant difference in hypotension (RR 1.74, 95% CI 0.85–3.58; p=0.13), bradycardia (RR 0.86, 95% CI 0.19–3.81; p=0.153) or events leading to drug discontinuation (RR 1.16, 95% CI 0.26–5.15; p=0.84). Assessment by beta-1 selectivity showed that hypotension and bradycardia were more frequent with non-selective beta-blockers (sotalol) than comparators (RR 4.57, 95% CI 1.92–10.85; p=0.001 and 5.97, 95% CI 1.34–26.57; p=0.019). Conclusion There is no difference between IV beta-blockers overall and other medications for the control of acute AF/AFl, although better efficacy was shown for beta-blockers with higher beta-1 selectivity. IV beta-blockers were as safe as comparator agents, with the exception of non-selective beta-blockers. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Independent systematic review commissioned by Amomed Pharma. Target heart rate and hypotension events

Efficacy and safety of pharmacological cachexia interventions: systematic review and network meta-analysis

2020 ◽  
pp. bmjspcare-2020-002601
Author(s):  
Manit Saeteaw ◽  
Phitjira Sanguanboonyaphong ◽  
Jukapun Yoodee ◽  
Kaitlyn Craft ◽  
Ratree Sawangjit ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Meta Analysis ◽  
Total Body Weight ◽  
Megestrol Acetate ◽  
High Dose ◽  
Efficacy And Safety ◽  
Pharmacological Interventions ◽  
Serious Adverse Events ◽  
Significant Difference

AimsRandomised controlled trials (RCTs) demonstrated benefits of pharmacological interventions for cachexia in improving weight and appetite. However, comparative efficacy and safety are not available. We conducted a systematic review and network meta-analysis (NMA) to evaluate the relative efficacy and safety of pharmacological interventions for cachexia.MethodsPubMed, EmBase, Cochrane, and ClinicalTrials.gov were searched for RCTs until October 2019. Key outcomes were total body weight (TBW) improvement, appetite (APP) score and serious adverse events. Two reviewers independently extracted data and assessed risk of bias. NMA was performed to estimate weight gain and APP score increase at 8 weeks, presented as mean difference (MD) or standardised MD with 95% CI.Results80 RCTs (10 579 patients) with 12 treatments were included. Majority is patients with cancer (7220). Compared with placebo, corticosteroids, high-dose megestrol acetate combination (Megace_H_Com) (≥400 mg/day), medroxyprogesterone, high-dose megestrol acetate (Megace_H) (≥400 mg/day), ghrelin mimetic and androgen analogues (Androgen) were significantly associated with MD of TBW of 6.45 (95% CI 2.45 to 10.45), 4.29 (95% CI 2.23 to 6.35), 3.18 (95% CI 0.94 to 5.41), 2.66 (95% CI 1.47 to 3.85), 1.73 (95% CI 0.27 to 3.20) and 1.50 (95% CI 0.56 to 2.44) kg. For appetite improvement, Megace_H_Com, Megace_H and Androgen significantly improved standardised APP score, compared with placebo. There is no significant difference in serious adverse events from all interventions compared with placebo.ConclusionsOur findings suggest that several pharmacological interventions have potential to offer benefits in treatment of cachexia especially Megace_H and short-term use corticosteroids. Nonetheless, high-quality comparative studies to compare safety and efficacy are warranted for better management of cachexia.

scholarly journals The efficacy and safety of prophylactic corticosteroids for the prevention of adverse outcomes in patients undergoing heart surgery using cardiopulmonary bypass: a systematic review and meta-analysis of randomized controlled trials

2020 ◽  
Vol 57 (4) ◽  
pp. 620-627 ◽  
Author(s):  
Ka Ting Ng ◽  
Judith Van Paassen ◽  
Clare Langan ◽  
Deep Pramod Sarode ◽  
M Sesmu Arbous ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Systematic Review ◽  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Adverse Events ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Site Infection ◽  
Efficacy And Safety ◽  
Randomized Controlled

Abstract Corticosteroids are often administered prophylactically to attenuate the inflammatory response associated with cardiac surgery using cardiopulmonary bypass (CPB). However, the efficacy and safety profile of corticosteroids remain uncertain. The primary aim of this systematic review and meta-analysis was to investigate the effect of corticosteroids on mortality in adult cardiac surgery using CPB. Secondary aims were to examine the effect of corticosteroids on myocardial adverse events, pulmonary adverse events, atrial fibrillation, surgical site infection, gastrointestinal bleeding and duration of stay in the intensive care unit and hospital. Randomized controlled trials (RCTs) were systematically searched in electronic databases (MEDLINE, EMBASE, CINAHL, CENTRAL and Web of Science) from their inception until March 2019. Observational studies, case reports, case series and literature reviews were excluded. Sixty-two studies (n = 16 457 patients) were included in this meta-analysis. There was no significant difference in mortality between the corticosteroid and placebo groups [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.81–1.14; P = 0.65, participants = 14 693, studies = 24, evidence of certainty: moderate]. Compared to those receiving a placebo, patients who were given corticosteroids had a significantly higher incidence of myocardial adverse events (OR 1.17, 95% CI 1.03–1.33; P = 0.01, participants = 14 512, studies = 23) and a lower incidence of pulmonary adverse events (OR 0.86, 95% CI 0.75–0.98; P = 0.02, participants = 13 426, studies = 17). The incidences of atrial fibrillation (OR 0.87, 95% CI 0.81–0.94; P < 0.001, participants = 14 148, studies = 24) and surgical site infection (OR 0.81, 95% CI 0.73–0.90; P < 0.001, participants = 13 946; studies = 22) were all lower in patients who were given corticosteroids. In the present meta-analysis of 62 RCTs (16 457 patients), including the 2 major RCTs (SIRS and DECS trials: 12 001 patients), we found that prophylactic corticosteroids in cardiac surgery did not reduce mortality. The clinical significance of an increase in myocardial adverse events remains unclear as the definition of a relevant myocardial end point following cardiac surgery varied greatly between RCTs.

scholarly journals Systematic review and meta-analysis of second-generation antidepressants for the treatment of older adults with depression: questionable benefit and considerations for frailty

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Laurie Mallery ◽  
Tanya MacLeod ◽  
Michael Allen ◽  
Pamela McLean-Veysey ◽  
Natasha Rodney-Cail ◽  
...  
Keyword(s):  
Systematic Review ◽  
Older Adults ◽  
Adverse Events ◽  
Second Generation ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Frail Older Adults ◽  
Significant Difference

Abstract Background Frail older adults are commonly prescribed antidepressants. Yet, there is little evidence to determine the efficacy and safety of antidepressants to treat depression with concomitant frailty. To better understand this issue, we examined the efficacy and safety of second-generation antidepressants for the treatment of older adults with depression and then considered implications for frailty. Methods Due to the absence of therapeutic studies of frail older adults with depression, we conducted a systematic review and meta-analysis of double-blind, randomized controlled trials that compared antidepressants versus placebo for adults with depression, age 65 years or older. We searched PubMed/MEDLINE, Cochrane Library, reference lists from meta-analyses/studies, hand searches of publication lists, and related articles on PubMed. Outcomes included rates of response, remission, and adverse events. After evaluating the data, we applied a frailty-informed framework to consider how the evidence could be applied to frailty. Results Nine trials were included in the meta-analysis (n = 2704). Subjects had moderate to severe depression. For older adults with depression, there was no statistically significant difference in response or remission to second-generation antidepressants compared to placebo. Response occurred in 45.3% of subjects receiving an antidepressant compared to 40.5% receiving placebo (RR 1.15, 95% CI: 0.96 – 1.37, p = 0.12, I2 = 71%). Remission occurred in 33.1% with antidepressant versus 31.3% with placebo (RR 1.10, 95% CI: 0.92 – 1.31, p = 0.30, I2 = 56%) (Figure 2 and 3). There were more withdrawals due to adverse events with antidepressants, 13% versus 5.8% (RR 2.30, 95% CI: 1.45–3.63; p < 0.001; I2 = 61%; NNH 14, 95% CI:10–28). Implications for frailty Subjects in the meta-analysis did not have obvious characteristics of frailty. Using framework questions to consider the implications of frailty, we hypothesize that, like older adults, frail individuals with depression may not respond to antidepressants. Further, observational studies suggest that those who are frail may be less responsive to antidepressants compared to the non-frail. Given the vulnerability of frailty, adverse events may be more burdensome. Conclusions Second-generation antidepressants have uncertain benefit for older adults with depression and cause more adverse events compared to placebo. Until further research clarifies benefit, careful consideration of antidepressant prescribing with frailty is warranted.

Efficacy and Safety of Antigen-specific Immunotherapy in the Treatment of Patients with Non-small-cell Lung Cancer: A Systematic Review and Meta-analysis

2019 ◽  
Vol 19 (3) ◽  
pp. 199-209 ◽  
Author(s):  
Bing-Di Yan ◽  
Xiao-Feng Cong ◽  
Sha-Sha Zhao ◽  
Meng Ren ◽  
Zi-Ling Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Specific Immunotherapy ◽  
Meta Analysis ◽  
Small Cell ◽  
Efficacy And Safety ◽  
Small Cell Lung

Background and Objective: We performed this systematic review and meta-analysis to assess the efficacy and safety of antigen-specific immunotherapy (Belagenpumatucel-L, MAGE-A3, L-BLP25, and TG4010) in the treatment of patients with non-small-cell lung cancer (NSCLC). </P><P> Methods: A comprehensive literature search on PubMed, Embase, and Web of Science was conducted. Eligible studies were clinical trials of patients with NSCLC who received the antigenspecific immunotherapy. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated for overall survival (OS), progression-free survival (PFS). Pooled risk ratios (RRs) were calculated for overall response rate (ORR) and the incidence of adverse events. </P><P> Results: In total, six randomized controlled trials (RCTs) with 4,806 patients were included. Pooled results showed that, antigen-specific immunotherapy did not significantly prolong OS (HR=0.92, 95%CI: 0.83, 1.01; P=0.087) and PFS (HR=0.93, 95%CI: 0.85, 1.01; P=0.088), but improved ORR (RR=1.72, 95%CI: 1.11, 2.68; P=0.016). Subgroup analysis based on treatment agents showed that, tecemotide was associated with a significant improvement in OS (HR=0.85, 95%CI: 0.74, 0.99; P=0.03) and PFS (HR=0.70, 95%CI: 0.49, 0.99, P=0.044); TG4010 was associated with an improvement in PFS (HR=0.87, 95%CI: 0.75, 1.00, P=0.058). In addition, NSCLC patients who were treated with antigen-specific immunotherapy exhibited a significantly higher incidence of adverse events than those treated with other treatments (RR=1.11, 95%CI: 1.00, 1.24; P=0.046). </P><P> Conclusion: Our study demonstrated the clinical survival benefits of tecemotide and TG4010 in the treatment of NSCLC. However, these evidence might be limited by potential biases. Therefore, further well-conducted, large-scale RCTs are needed to verify our findings.

Inhaled Levodopa (CVT-301) for the Treatment of Parkinson Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials

2021 ◽  
pp. 10.1212/CPJ.0000000000001143
Author(s):  
Glenardi Glenardi ◽  
Tutwuri Handayani ◽  
Jimmy Barus ◽  
Ghea Mangkuliguna
Keyword(s):  
Systematic Review ◽  
Placebo Group ◽  
Adverse Events ◽  
Respiratory Symptoms ◽  
Meta Analysis ◽  
Motor Fluctuation ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
Improve Motor Function

ABSTRACTPurposeof Review: To investigate the efficacy and safety of CVT-301 for motor fluctuation in Parkinson’s disease (PD).Recent Findings:This study demonstrated that the CVT-301 group had a higher proportion of patients achieving an ON state than the placebo group (OR=2.68; 95% CI: 1.86-3.86; p<0.00001). Moreover, CVT-301 had also shown to improve motor function by UPDRS-III score (SMD=3.83; 95% CI: 2.44-5.23; p<0.00001) and promote an overall improvement of PD by PGIC self-rating (OR=2.95; 95% CI: 1.78-4.9; p<0.00001). The most common adverse events encountered were respiratory symptoms (OR=12.18; 95% CI: 5.01-29.62; p<0.00001) and nausea (OR=3.95; 95% CI: 1.01-15.41; p=0.05).Summary:CVT-301 had the potential to be an alternative or even a preferred treatment for motor fluctuation in PD patients.

scholarly journals Racecadotril for acute diarrhoea in children: systematic review and meta-analyses

2015 ◽  
Vol 101 (3) ◽  
pp. 234-240 ◽  
Author(s):  
Morris Gordon ◽  
Anthony Akobeng
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Methodological Quality ◽  
Data Extraction ◽  
Meta Analysis ◽  
Acute Diarrhoea ◽  
Risk Of Bias ◽  
Duration Of Symptoms ◽  
Duration Of Illness ◽  
Significant Difference

ObjectiveRacecadotril is an antisecretory agent that can prevent fluid/electrolyte depletion from the bowel as a result of acute diarrhoea without affecting intestinal motility. An up-to-date systematic review is indicated to summarise the evidence on racecadotril for the treatment of acute diarrhoea in children.DesignA Cochrane format systematic review of randomised controlled trials (RCTs). Data extraction and assessment of methodological quality were performed independently by two reviewers. Methodological quality was assessed using the Cochrane risk of bias tool.PatientsChildren with acute diarrhoea, as defined by the primary studies.InterventionsRCTs comparing racecadotril with placebo or other interventions.Main outcome measursDuration of illness, stool output/volume and adverse events.ResultsSeven RCTs were included, five comparing racecadotril with placebo or no intervention, one with pectin/kaolin and one with loperamide. Moderate to high risk of bias was present in all studies. There was no significant difference in efficacy or adverse events between racecadotril and loperamide. A meta-analysis of three studies with 642 participants showed significantly shorter duration of symptoms with racecadotril compared with placebo (mean difference −53.48 h, 95% CI −65.64 to −41.33). A meta-analysis of five studies with 949 participants showed no significant difference in adverse events between racecadotril and placebo (risk ratio 0.99, 95% CI 0.73 to 1.34).ConclusionsThere is some evidence that racecadotril is more effective than placebo or no intervention in reducing the duration of illness and stool output in children with acute diarrhoea. However, the overall quality of the evidence is limited due to sparse data, heterogeneity and risk of bias. Racecadotril appears to be safe and well tolerated.

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