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 Fecal Microbiota Transplantation as Therapy for Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Xiaolei Liu ◽  
Yan Li ◽  
Kaichun Wu ◽  
Yongquan Shi ◽  
Min Chen
Keyword(s):  
Systematic Review ◽  
Ulcerative Colitis ◽  
Adverse Events ◽  
Clinical Remission ◽  
Fecal Microbiota Transplantation ◽  
Meta Analysis ◽  
Fecal Microbiota ◽  
Serious Adverse Events ◽  
Significant Difference ◽  
Endoscopic Remission

Aim. Increasing evidence supports the role of the gut microbiota in the etiology of ulcerative colitis (UC). Fecal microbiota transplantation (FMT) is a highly effective treatment against recurrent Clostridium difficile infection; however, its efficacy in UC is still controversial. A systematic review and meta-analysis was conducted to evaluate the efficacy and safety of FMT for treatment of active UC. Methods. We searched Cochrane, Medline, Web of Science, and Embase from inception to February 2020. Randomized controlled trials (RCTs) recruiting adults with active UC, which compared FMT with controls, were eligible. The primary outcome was combined clinical remission with endoscopic remission/response. Secondary outcomes included clinical remission, endoscopic remission, and serious adverse events. Relative risk (RR) with 95% confidence interval (CI) is reported. Results. Five RCTs with 292 participants were eligible for inclusion. When data were pooled for all patients, FMT was associated with a higher combined clinical remission with endoscopic remission/response; the RR of combined outcome not achieving after FMT vs. control was 0.79 (95% CI 0.70-0.88). FMT delivered via lower gastrointestinal route was superior to upper gastrointestinal route with regard to combined clinical remission with endoscopic remission/response ( RR = 0.79 , 95% CI 0.70-0.89). FMT with pooled donor stool ( RR = 0.69 , 95% CI 0.56-0.85) and higher frequency of administration ( RR = 0.76 , 95% CI 0.62-0.93) may be more effective with regard to clinical remission. There was no statistically significant difference in serious adverse events with FMT compared with controls ( RR = 0.98 , 95% CI 0.93-1.03). Conclusion. FMT shows a promising perspective with comparable safety and favorable clinical efficacy for the treatment of active UC in the short term. However, further larger, more rigorously conducted RCTs of FMT in UC are still needed in order to resolve the controversial questions.

scholarly journals Efficacy and safety of low-dose versus high-dose hydrocortisone to treat hypotension in neonates: a protocol for a systematic review and meta-analysis

2021 ◽  
Vol 5 (1) ◽  
pp. e001200
Author(s):  
Katelyn Sushko ◽  
Nada Al-Rawahi ◽  
Kristi Watterberg ◽  
John Van Den Anker ◽  
Catherine Litalien ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Critically Ill ◽  
Systematic Reviews ◽  
Meta Analysis ◽  
Adrenal Function ◽  
High Dose ◽  
Cochrane Central Register ◽  
Efficacy And Safety ◽  
Registration Number

BackgroundImpaired adrenal function is a well-described entity in critically ill term and preterm neonates with systemic hypotension. The standard treatment for neonatal hypotension includes volume expanders and vasopressors. Recent evidence supports the use of glucocorticoids for the primary or rescue treatment of neonatal hypotension associated with impaired adrenal function. However, inconsistency regarding the prescribed dosing regimen to provide the best balance between efficacy and safety in this vulnerable population remains an area of concern.MethodsWe will conduct a systematic review and meta-analysis to evaluate low-dosing compared with high-dosing regimens of hydrocortisone for the treatment of hypotension in critically ill term, preterm and very low birth weight neonates. Ovid MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and Web of Science will be searched from inception to November 2021. Study screening and selection will be completed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Our primary outcomes will be (1) an improvement in end-organ perfusion, defined as an increase in blood pressure along with an increase in urine output or a reduction in serum lactate and (2) mortality prior to discharge. Our secondary outcomes will be the development of (1) major neurosensory abnormality, (2) bronchopulmonary dysplasia and (3) the occurrence of adverse events.DiscussionHydrocortisone may be beneficial in the treatment of hypotension associated with impaired adrenal function among critically ill neonates. However, its optimal dosing to balance desired efficacy with the risk of adverse events is yet to be determined. Our systematic review and meta-analysis aims to address this evidence gap, providing valuable knowledge for a large audience, including guideline developers, policy-makers and clinicians.PROSPERO registration numberThis protocol is submitted for registration to the international database of prospectively registered systematic reviews (PROSPERO, awaiting registration number).

scholarly journals The safety, tolerability and mortality reduction efficacy of remdesivir; based on randomized clinical trials, observational and case studies reported safety outcomes: an updated systematic review and meta-analysis

2021 ◽  
Vol 12 ◽  
pp. 204209862110425
Author(s):  
Chenchula Santenna ◽  
Kota Vidyasagar ◽  
Krishna Chaitanya Amarneni ◽  
Sai Nikhila Ghanta ◽  
Balakrishnan Sadasivam ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Antiviral Drug ◽  
Mortality Reduction ◽  
Serious Adverse Events ◽  
Significant Difference ◽  
Grade 3

Introduction: Remdesivir, an experimental antiviral drug has shown to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), both in vitro and in vivo. The present systematic review and meta-analysis were performed to quantify the safety and tolerability of remdesivir, based on safety outcome findings from randomized controlled trials, observational studies and case reports of remdesivir in coronavirus disease 2019 (COVID-19) patients. Methods: We have performed a systematic search in the PubMed, Google Scholar and Cochrane Library using specific keywords such as ‘COVID-19’ OR ‘SARS CoV-2’ AND ‘Remdesivir’. The study endpoints include total adverse events (AEs), serious adverse events (SAEs), grade 3 and grade 4 AEs, mortality and drug tolerability. Statistical analysis was carried out by using Revman 5.4 software. Results: Total 15 studies were included for systematic review, but only 5 randomized clinical trials (RCTs) ( n = 13,622) were included for meta-analysis. Visual inspection of the forest plots for remdesivir 10-day versus placebo and remdesivir 10-day versus 5-day groups revealed that there is a significant difference in SAEs [10-day remdesivir versus control (odds ratio [OR] = 0.55, 0.40–0.74) p = 0.0001; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 0.56, 0.38–0.84) p = 0.005; I2 = 13%]. In grade 4 AEs, there is a significant difference in 10-day remdesivir versus control (OR = 0.32, 0.19–0.54) p = 0.0001; I2 = 0%, but not in comparison to 5-day remdesivir (OR = 0.95, 0.59–1.54) p = 0.85; I2 = 0%. But there is no significant difference in grade 3 AEs [remdesivir 10 day versus control (OR = 0.81, 0.59–1.11) p = 0.19; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 1.24, 0.86–1.80) p = 0.25; I2 = 0%], in total AEs [remdesivir 10 day versus control (OR = 1.07, 0.66–1.75) p = 0.77; I2 = 79%; remdesivir 10 day versus 5 day (OR = 1.08, 0.70–1.68) p = 0.73; I2 = 54%)], in mortality [10-day remdesivir versus control (OR = 0.93, 0.80–1.08) p = 0.32; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 1.39, 0.73–2.62) p = 0.32; I2 = 0%)] and tolerability [remdesivir 10 day versus control (OR = 1.05, 0.51–2.18) p = 0.89; I2 = 65%, 10-day remdesivir versus 5-day remdesivir (OR = 0.86, 0.18–4.01) p = 0.85; I2 = 78%]. Discussion & Conclusion: Ten-day remdesivir was a safe antiviral agent but not tolerable over control in the hospitalized COVID-19 patients with a need of administration cautiousness for grade 3 AEs. There was no added benefit of 10- or 5-day remdesivir in reducing mortality over placebo. To avoid SAEs, we suggest for prior monitoring of liver function tests (LFT), renal function tests (RFT), complete blood count (CBC) and serum electrolytes for those with preexisting hepatic and renal impairments and patients receiving concomitant hepatotoxic or nephrotoxic drugs. Furthermore, a number of RCTs of remdesivir in COVID-19 patients are suggested. Plain Language Summary Ten-day remdesivir is a safe antiviral drug with common adverse events in comparison to placebo. The rate of serious adverse events and grade 3 adverse events were significantly lower in 10-day remdesivir in comparison to placebo/5-day remdesivir. There was no significant difference in the rate of tolerability and mortality reduction in 10-day remdesivir over placebo/5-day remdesivir. There were no new safety signals reported in vulnerable populations, paediatric, pregnant and lactating women.

scholarly journals Comparative Effectiveness of Pharmacological Interventions for Covid-19: A Systematic Review and Network Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Franco De Crescenzo ◽  
Laura Amato ◽  
Fabio Cruciani ◽  
Luke P Moynihan ◽  
Gian Loreto D’Alò ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Pharmacological Intervention ◽  
Pharmacological Interventions ◽  
Serious Adverse Events ◽  
All Cause Mortality ◽  
Randomised Controlled

Background: Several pharmacological interventions are now under investigation for the treatment of Covid-19, and the evidence is evolving rapidly. Our aim is to assess the comparative efficacy and safety of these drugs.Methods and Findings: We performed a systematic review and network meta-analysis searching Medline, Pubmed, Embase, Cochrane Covid-19 register, international trial registers, medRxiv, bioRxiv, and arXiv up to December 10, 2020. We included all randomised controlled trials (RCTs) comparing any pharmacological intervention for Covid-19 against any drugs, placebo or standard care (SC). Data extracted from published reports were assessed for risk of bias in accordance with the Cochrane tool, and using the GRADE framework. Primary outcomes were all-cause mortality, adverse events (AEs) and serious adverse events (SAEs). We estimated summary risk ratio (RR) using pairwise and network meta-analysis with random effects (Prospero, number CRD42020176914). We performed a systematic review and network meta-analysis searching Medline, Pubmed, Embase, Cochrane Covid-19 register, international trial registers, medRxiv, bioRxiv, and arXiv up to December 10, 2020. We included all randomised controlled trials (RCTs) comparing any pharmacological intervention for Covid-19 against any drugs, placebo or standard care (SC). Data extracted from published reports were assessed for risk of bias in accordance with the Cochrane tool, and using the GRADE framework. Primary outcomes were all-cause mortality, adverse events (AEs) and serious adverse events (SAEs). We estimated summary risk ratio (RR) using pairwise and network meta-analysis with random effects (Prospero, number CRD42020176914). We included 96 RCTs, comprising of 34,501 patients. The network meta-analysis showed in terms of all-cause mortality, when compared to SC or placebo, only corticosteroids significantly reduced the mortality rate (RR 0.90, 95%CI 0.83, 0.97; moderate certainty of evidence). Corticosteroids significantly reduced the mortality rate also when compared to hydroxychloroquine (RR 0.83, 95%CI 0.74, 0.94; moderate certainty of evidence). Remdesivir proved to be better in terms of SAEs when compared to SC or placebo (RR 0.75, 95%CI 0.63, 0.89; high certainty of evidence) and plasma (RR 0.57, 95%CI 0.34, 0.94; high certainty of evidence). The combination of lopinavir and ritonavir proved to reduce SAEs when compared to plasma (RR 0.49, 95%CI 0.25, 0.95; high certainty of evidence). Most of the RCTs were at unclear risk of bias (42 of 96), one third were at high risk of bias (34 of 96) and 20 were at low risk of bias. Certainty of evidence ranged from high to very low.Conclusion: At present, corticosteroids reduced all-cause mortality in patients with Covid-19, with a moderate certainty of evidence. Remdesivir appeared to be a safer option than SC or placebo, while plasma was associated with safety concerns. These preliminary evidence-based observations should guide clinical practice until more data are made public.

scholarly journals Efficacy and Safety of Daprodustat for Anemia Therapy in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Qiyan Zheng ◽  
Yahui Wang ◽  
Huisheng Yang ◽  
Luying Sun ◽  
Xinwen Fu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Binding Capacity ◽  
Meta Analysis ◽  
Transferrin Saturation ◽  
Placebo Treatment ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Significant Difference

Objective: Daprodustat is a novel oral agent in treating anemia of chronic kidney disease (CKD), and several clinical trials have been conducted to compare daprodustat with recombinant human erythropoietin (rhEPO) or placebo. Our systematic review aimed to investigate the efficacy and safety of daprodustat for anemia treatment in both dialysis-dependent (DD) and non-dialysis-dependent (NDD) patients.Methods: Six databases were searched for randomized controlled trials (RCTs) reporting daprodustat vs. rhEPO or placebo for anemia patients in CKD. The outcome indicators were focused on hemoglobin (Hb), ferritin, transferrin saturation (TSAT), total iron-binding capacity (TIBC), vascular endothelial growth factor (VEGF), and serious adverse events (SAEs).Results: Eight eligible studies with 1,516 participants were included. For both NDD and DD patients, changes in Hb levels from baseline were significantly higher in daprodustat group than that in the placebo (mean difference (MD) = 1.73, [95% confidence interval (CI), 0.34 to 3.12], p = 0.01; MD = 1.88, [95% CI, 0.68 to 3.09], p = 0.002; respectively), and there was no significant difference between daprodustat and rhEPO group (MD = 0.05, [95% CI, −0.49 to 0.59], p = 0.86; MD = 0.12, [95% CI, −0.28 to 0.52], p = 0.55; respectively). The indexes of iron metabolism were improved significantly in the daprodustat group compared to placebo- or rhEPO-treated patients, while there was no similar change in terms of TSAT for DD patients. Furthermore, no trend of increasing plasma VEGF was observed in daprodustat-treated subjects. As for safety, there was no significant difference in the incidence of SAEs between daprodustat and placebo treatment, while the incidence of SAEs in the daprodustat group was significantly lower than that in the rhEPO group.Conclusion: Daprodustat was efficacious and well tolerated for anemia in both NDD and DD patients in the short term based on current RCTs. And daprodustat may become an effective alternative for treatment of anemia with CKD. Since the application of daprodustat is still under exploration, future researches should consider the limitations of our study to evaluate the value of daprodustat.

scholarly journals Optimal treatment strategy of fremanezumab in migraine prevention: a systematic review with network meta-analysis of randomized clinical trials

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
I-Hsin Huang ◽  
Po-Chien Wu ◽  
Ya-Han Lee ◽  
Yi-No Kang
Keyword(s):  
Adverse Events ◽  
Treatment Strategy ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Reduction Rate ◽  
High Dose ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Mean Differences

Abstract Identifying the optimal fremanezumab treatment strategy is crucial in treating patients with migraines. The optimal strategy was investigated by assessing the cumulative 50% reduction rate (50%CRR), cumulative 75% reduction rate (75%CRR), reduction in the number of migraine days, treatment-related adverse events, and serious adverse events in patients treated with fremanezumab 225 mg monthly (225 mg), 675 mg monthly (675 mg), 900 mg monthly (900 mg), a single high dose of 675 mg (S675mg), 675 mg at baseline with 225 mg monthly (675/225 mg), and placebo. Biomedical databases were searched for randomized controlled trials on this topic, and data were individually extracted. Risk ratios and mean differences were used to present the pooled results. The surface under the cumulative ranking curve (SUCRA) was used to determine the effects of the medication strategies of fremanezumab. Five trials (n = 3404) were used to form a six-node network meta-analysis. All fremanezumab medication strategies displayed significantly higher cumulative 50% reduction rates than the placebo. The SUCRA revealed that treatment with 675 mg yielded the highest 50%CRR value (mean rank = 2.5). S675 mg was the only treatment with significantly higher 75%CRR reduction rate than placebo, whereas the SUCRA for 225 mg displayed the highest mean rank (2.2). Moreover, 225 mg (mean rank = 2.2) and S675 mg (mean rank = 2.2) presented lower probabilities of serious adverse events. Collectively, S675mg and 225 mg exhibited the optimal balance between efficacy and safety within three months. Long-term efficacy and safety remain unclear, and future studies should further evaluate the long-term outcomes.

scholarly journals Enough with the madness: a systematic review and meta-analysis of hydroxychloroquine for COVID-19

2021 ◽  
Vol 13 (2) ◽  
pp. 186-220
Author(s):  
André Santos ◽  
◽  
Érica Gonçalves ◽  
Ananda Oliveira ◽  
Douglas Lima ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Meta Analysis ◽  
Standard Of Care ◽  
P Value ◽  
Serious Adverse Events ◽  
Risk Of Death ◽  
Increased Risk ◽  
Significant Difference

Objective: Because of preliminary results from in vitro studies, hydroxychloroquine (HCQ) and chloroquine (CQ) have been proposed as possible treatments for COVID-19, but the clinical evidence is discordant. This study aims to evaluate the safety and efficacy of CQ and HCQ for the treatment of COVID-19. Methods: A systematic review with meta-analysis was performed. An electronic search was conducted in four databases for randomized controlled trials that compared HCQ or CQ with standard-of-care. A complementary search was performed. A quantitative synthesis of clinical outcomes was performed using the inverse variance method adjusting for a random-effects model. Results: In total, 16 studies were included. The meta-analysis found no significant difference between intervention and control groups in terms of mortality at the most extended follow-up (RR = 1.09, CI95% = 0.99-1.19, p-value = 0.08), patients with negative PCR results (RR = 0.99, CI95% = 0.89-1.10, p-value = 0.86), or serious adverse events (RR = 2.21, CI95% = 0.89-5.47, p-value = 0.09). HCQ was associated with an increased risk of adverse events (RR = 2.28, CI95% = 1.36-2.83, p-value < 0.01). The quality of evidence varied from very low to high. Conclusion: There is no evidence that HCQ reduces the risk of death or improves cure rates in patients with COVID-19, but it might be associated with an increased risk of adverse events

scholarly journals Systematic Review and Meta-analysis of the Safety of Chloroquine and Hydroxychloroquine From Randomized Controlled Trials on Malarial and Non-malarial Conditions

2020 ◽  
Author(s):  
Mayra Souza Botelho ◽  
Fernanda Bolfi ◽  
Renata Giacomini Occhiuto Ferreira Leite ◽  
Mauro Salles Ferreira Leite ◽  
Luisa Rocco Banzato ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Evaluation System ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Low Frequency ◽  
Cardiac Complications ◽  
Serious Adverse Events ◽  
Significant Difference ◽  
Meta Analyses

Abstract Background: Despite the expectations regarding the effectiveness of chloroquine (CQ) and hydroxychloroquine (HCQ) for coronavirus disease (COVID-19) management, concerns about their adverse events have remained. Objectives: The objective of this systematic review was to evaluate the safety of CQ and HCQ from malarial and non-malarial randomized clinical trials (RCTs). Methods: The primary outcomes were the frequencies of serious adverse events (SAEs), retinopathy, and cardiac complications. Search strategies were applied to MEDLINE, EMBASE, LILACS, CENTRAL, Scopus, and Trip databases. We used random-effects model to pool results across studies and Peto one-step odds ratio (OR) for event rates below 1 %. Both-armed zero-event studies were excluded from the meta-analyses. We used the Grading of Recommendations Assessment, Development, and Evaluation system to evaluate the certainty of evidence.Results: Ninety-two RCTs were included. We found no significant difference between CQ/HCQ and control (placebo or non-CQ/HCQ) in the frequency of SAEs (OR: 0.98, 95 % confidence interval [CI]: 0.71–1.36, 25 trials, 11,605 participants, moderate certainty of evidence). No clear relationship was observed between CQ/HCQ and retinopathy (OR: 1,63, 95 % CI: -0.4–6.57, 5 trials, 344 participants, very low certainty of evidence). There was a low certainty of evidence of the effect of CQ/HCQ versus control on cardiac complications (Relative risk: 1.48, 95 % CI: 1.1–1.98, 8 trials, 5,970 participants).Conclusions: CQ and HCQ might be safe, with low frequency of SAEs on malarial and non-malarial conditions. No clear effect of their use on the incidence of retinopathy and cardiac complications was observed.The protocol for this systematic review was registered with PROSPERO (registration number: CRD42020177818)

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&lt;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&lt;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

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.

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