Dual– Versus Mono–Bronchodilator Therapy in Moderate to Severe COPD: A Meta-analysis

2020 ◽  
Vol 54 (12) ◽  
pp. 1232-1242
Author(s):  
Melissa Lipari ◽  
Pramodini B. Kale-Pradhan ◽  
Sheila M. Wilhelm
Keyword(s):  
Adverse Events ◽  
English Language ◽  
Meta Analysis ◽  
Dual Therapy ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Jadad Score ◽  
Serious Adverse Events ◽  
Bronchodilator Therapy ◽  
Long Acting

Background: Chronic obstructive pulmonary disease (COPD) guidelines recommend both long-acting and dual bronchodilator therapy. It is unclear if there are differences in efficacy and safety. Objective: This meta-analysis evaluates the efficacy of dual therapy with long-acting β-agonist (LABA) + long acting muscarinic antagonist (LAMA) compared with monotherapy with LAMA for COPD. Methods: We searched PubMed, CINAHL, and Web of Science databases from inception through March 2020 to identify English-language, prospective randomized controlled trials (RCTs) that compared dual therapy with monotherapy in adult patients with COPD. Risk of bias was assessed using the Jadad score. Overall analysis was performed using Review Manager 5.3. Treatment effect was determined with the random-effects model using the Mantel-Haenszel method and was reported as mean difference (MD) with 95% CI. Results: A total of 18 RCTs were included (n = 6086; median Jadad score 5/5) that compared LAMA + LABA with LAMA. There was a greater improvement in forced expiratory volume at 1 s (FEV1) with dual therapy compared with LAMA: MD = 0.08; 95% CI = [0.05, 0.11]. There was no difference in St George Respiratory Questionnaire (SGRQ) scores between groups: OR = −0.85; 95% CI = [−1.83, 0.13]. There were no differences in overall adverse events (OR = 1.00; 95% CI = 0.92, 1.09), serious adverse events (OR = 1.01; 95% CI = 0.86, 1.18), or cardiovascular events (OR = 0.88; 95% CI = 0.58, 1.34). Conclusion and Relevance: Dual therapy improves FEV1 and is as safe as LAMA. Dual therapy does not improve SGRQ scores more than LAMA.

scholarly journals Long-acting muscarinic antagonists vs. long-acting β 2 agonists in COPD exacerbations: a systematic review and meta-analysis

2017 ◽  
Vol 43 (4) ◽  
pp. 302-312 ◽  
Author(s):  
Israel Silva Maia ◽  
Mariângela Pimentel Pincelli ◽  
Victor Figueiredo Leite ◽  
João Amadera ◽  
Anna Maria Buehler
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Therapeutic Effects ◽  
Muscarinic Antagonists ◽  
Serious Adverse Events ◽  
Exacerbation Rate ◽  
Copd Exacerbations ◽  
Long Acting

ABSTRACT Objective: To determine whether long-acting muscarinic antagonists (LAMAs) provide superior therapeutic effects over long-acting β2 agonists (LABAs) for preventing COPD exacerbations. Methods: This was a systematic review and meta-analysis of randomized clinical trials involving patients with stable, moderate to severe COPD according to the Global Initiative for Chronic Obstructive Lung Disease criteria, treated with a LAMA (i.e., tiotropium bromide, aclidinium, or glycopyrronium), followed for at least 12 weeks and compared with controls using a LABA in isolation or in combination with a corticosteroid. Results: A total of 2,622 studies were analyzed for possible inclusion on the basis of their title and abstract; 9 studies (17,120 participants) were included in the analysis. In comparison with LABAs, LAMAs led to a greater decrease in the exacerbation rate ratio (relative risk [RR] = 0.88; 95% CI: 0.84-0.93]; a lower proportion of patients who experienced at least one exacerbation (RR = 0.90; 95% CI: 0.87-0.94; p < 0.00001); a lower risk of exacerbation-related hospitalizations (RR = 0.78; 95% CI: 0.69-0.87; p < 0.0001); and a lower number of serious adverse events (RR = 0.81; 95% CI: 0.67-0.96; p = 0.0002). The overall quality of evidence was moderate for all outcomes. Conclusions: The major findings of this systematic review and meta-analysis were that LAMAs significantly reduced the exacerbation rate (exacerbation episodes/year), as well as the number of exacerbation episodes, of hospitalizations, and of serious adverse events.

scholarly journals Efficacy and safety profile of xanthines in COPD: a network meta-analysis

2018 ◽  
Vol 27 (148) ◽  
pp. 180010 ◽  
Author(s):  
Mario Cazzola ◽  
Luigino Calzetta ◽  
Peter J. Barnes ◽  
Gerard J. Criner ◽  
Fernando J. Martinez ◽  
...  
Keyword(s):  
Adverse Events ◽  
Safety Profile ◽  
Meta Analysis ◽  
Forced Expiratory Volume ◽  
Therapeutic Window ◽  
Comparable Efficacy ◽  
Chronic Obstructive ◽  
Efficacy And Safety ◽  
Quantitative Synthesis ◽  
The Impact

Theophylline can still have a role in the management of stable chronic obstructive pulmonary disease (COPD), but its use remains controversial, mainly due to its narrow therapeutic window. Doxofylline, another xanthine, is an effective bronchodilator and displays a better safety profile than theophylline. Therefore, we performed a quantitative synthesis to compare the efficacy and safety profile of different xanthines in COPD.The primary end-point of this meta-analysis was the impact of xanthines on lung function. In addition, we assessed the risk of adverse events by normalising data on safety as a function of person-weeks. Data obtained from 998 COPD patients were selected from 14 studies and meta-analysed using a network approach.The combined surface under the cumulative ranking curve (SUCRA) analysis of efficacy (change from baseline in forced expiratory volume in 1 s) and safety (risk of adverse events) showed that doxofylline was superior to aminophylline (comparable efficacy and significantly better safety), bamiphylline (significantly better efficacy and comparable safety), and theophylline (comparable efficacy and significantly better safety).Considering the overall efficacy/safety profile of the investigated agents, the results of this quantitative synthesis suggest that doxofylline seems to be the best xanthine for the treatment of COPD.

scholarly journals LABA/LAMA combination in COPD: a meta-analysis on the duration of treatment

2017 ◽  
Vol 26 (143) ◽  
pp. 160043 ◽  
Author(s):  
Luigino Calzetta ◽  
Paola Rogliani ◽  
Josuel Ora ◽  
Ermanno Puxeddu ◽  
Mario Cazzola ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Treatment Options ◽  
Forced Expiratory Volume ◽  
Fixed Dose ◽  
Chronic Obstructive ◽  
Duration Of Treatment ◽  
Eligibility Criteria ◽  
Treatment Comparison ◽  
Long Acting ◽  
Meta Analyses

When there are no randomised clinical trials directly comparing all relevant treatment options, an indirect treatment comparison via meta-analysis of the available clinical evidence is an acceptable alternative. However, meta-analyses may be very misleading if not adequately performed. Here, we propose and validate a simple and effective approach to meta-analysis for exploring the effectiveness of long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combinations in chronic obstructive pulmonary disease.14 articles with 20 329 patients (combinations n=9292; monocomponents n=11 037) were included in this study. LABA/LAMA combinations were always more effective than the monocomponents in terms of the improvement in trough forced expiratory volume in 1 s, transition dyspnoea index and St George's Respiratory Questionnaire scores after 3, 6 and 12 months of treatment. No significant publication bias was identified. Significant discrepancies with previous network meta-analyses have been found, with overall differences ranging from 26.7% to 43.3%.Results from previous network meta-analyses were misleading because no adequate attention was given to formulating the review question, specifying eligibility criteria, correctly identifying studies, collecting appropriate information and deciding what it would be pharmacologically relevant to analyse. The real gradient of effectiveness of LABA/LAMA fixed-dose combinations remains an unmet medical need; however, it can be investigated indirectly using a high-quality meta-analytic approach.

scholarly journals Triple therapy in the management of chronic obstructive pulmonary disease: systematic review and meta-analysis

BMJ ◽  
2018 ◽  
pp. k4388 ◽  
Author(s):  
Yayuan Zheng ◽  
Jianhong Zhu ◽  
Yuyu Liu ◽  
Weiguang Lai ◽  
Chunyu Lin ◽  
...  
Keyword(s):  
Triple Therapy ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Dual Therapy ◽  
Chronic Obstructive ◽  
Controlled Trials ◽  
Obstructive Pulmonary Disease ◽  
Long Acting ◽  
Randomised Controlled

AbstractObjectiveTo compare the rate of moderate to severe exacerbations between triple therapy and dual therapy or monotherapy in patients with chronic obstructive pulmonary disease (COPD).DesignSystematic review and meta-analysis of randomised controlled trials.Data sourcesPubMed, Embase, Cochrane databases, and clinical trial registries searched from inception to April 2018.Eligibility criteriaRandomised controlled trials comparing triple therapy with dual therapy or monotherapy in patients with COPD were eligible. Efficacy and safety outcomes of interest were also available.Data extraction and synthesisData were collected independently. Meta-analyses were conducted to calculate rate ratios, hazard ratios, risk ratios, and mean differences with 95% confidence intervals. Quality of evidence was summarised in accordance with GRADE methodology (grading of recommendations assessment, development, and evaluation).Results21 trials (19 publications) were included. Triple therapy consisted of a long acting muscarinic antagonist (LAMA), long acting β agonist (LABA), and inhaled corticosteroid (ICS). Triple therapy was associated with a significantly reduced rate of moderate or severe exacerbations compared with LAMA monotherapy (rate ratio 0.71, 95% confidence interval 0.60 to 0.85), LAMA and LABA (0.78, 0.70 to 0.88), and ICS and LABA (0.77, 0.66 to 0.91). Trough forced expiratory volume in 1 second (FEV1) and quality of life were favourable with triple therapy. The overall safety profile of triple therapy is reassuring, but pneumonia was significantly higher with triple therapy than with dual therapy of LAMA and LABA (relative risk 1.53, 95% confidence interval 1.25 to 1.87).ConclusionsUse of triple therapy resulted in a lower rate of moderate or severe exacerbations of COPD, better lung function, and better health related quality of life than dual therapy or monotherapy in patients with advanced COPD.Study registrationProspero CRD42018077033.

scholarly journals Efficacy and cardiovascular safety of LAMA in patients with COPD: a systematic review and meta-analysis

2021 ◽  
pp. jim-2021-001931
Author(s):  
Chuchu Zhang ◽  
Meng Zhang ◽  
Yalei Wang ◽  
Huaiyu Xiong ◽  
Qiangru Huang ◽  
...  
Keyword(s):  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Forced Expiratory Volume ◽  
Cochrane Library ◽  
Chronic Obstructive ◽  
Cardiovascular Safety ◽  
Obstructive Pulmonary Disease ◽  
Significant Difference ◽  
St George's Respiratory Questionnaire ◽  
Long Acting

Chronic obstructive pulmonary disease (COPD) is at present the third leading cause of death in the world. Long-acting muscarinic antagonist (LAMA) is widely used as a bronchodilator in patients with COPD. However, there is controversy concerning their cardiovascular safety. This meta-analysis aims to assess the efficacy and cardiovascular safety of LAMAs versus placebo in patients with COPD. We searched Pub Med, Embase, Cochrane Library, and Web of Science to identify studies that compared LAMA with placebo in patients with COPD. Twenty-one studies involving 24,987 participants were finally included in the analysis. There was no significant difference in the incidence of all adverse events (risk ratio (RR)=1.01, 95% CI 1.00 to 1.02, I2=15.2%) and cardiovascular events (RR=0.98, 95% CI 0.88 to 1.09, I2=4.9%) in patients treated with LAMAs versus placebo. LAMAs significantly improved trough forced expiratory volume in 1 s (weighted mean difference (WMD)=0.12, 95% CI 0.10 to 0.14, I2=86.6%), Transitional Dyspnea Index (WMD=0.75, 95% CI 0.56 to 0.94, I2=0%), and St. George’s Respiratory Questionnaire (WMD=‒2.50, 95% CI ‒3.32 to ‒1.69, I2=39.8%). Moreover, LAMAs significantly reduced the incidence of exacerbation in patients with COPD (RR=0.85, 95% CI 0.79 to 0.91, I2=69.9%). LAMAs are safe therapy and play a pivotal role in improving lung function, dyspnea, and health status, and reducing the exacerbation in patients with COPD.

scholarly journals Comparative Effectiveness and Safety of Seven Qi-Tonifying Chinese Medicine Injections for AECOPD Patients: A Systematic Review and Network Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Xueyi Deng ◽  
Fuqin Kang ◽  
Xueyin Chen ◽  
Jiaqi Lai ◽  
Xuanchen Guan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Chinese Medicine ◽  
Adverse Events ◽  
Comparative Effectiveness ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Small Sample ◽  
Cochrane Library ◽  
Chronic Obstructive ◽  
Serious Adverse Events

Introduction. Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) imposes a large burden on economy and society worldwide. In addition to western medicine, multiple kinds of qi-tonifying Chinese medicine injections have been widely used in China as adjunctive treatments. Previous small-sample clinical trials have proven their efficacy in the treatment of AECOPD. However, data on comparative effectiveness and safety of qi-tonifying injections are limited. We conducted this network meta-analysis to compare the efficacy and safety of 7 commonly used qi-tonifying injections in patients with AECOPD. Methods. Literature search was conducted through electronic databases, including PubMed, the Cochrane Library, EMBASE, CINAHL, AMED, CBM, CNKI, Wanfang database, and VIP database. Randomized clinical trials (RCTs) exploring the efficacy of any of these 7 qi-tonifying injections were included. The primary outcome was lung function (FEV1 and FVC). R 4.0.0 and STATA 12.0 were adopted to perform the network meta-analysis using Bayesian statistics. Results. A total of 36 RCTs involving 2657 participants were included. The results of network meta-analyses indicated that Chuankezhi injection (CKZ) combined with routine treatment (RT) was superior to other qi-tonifying injections combined with RT in terms of FEV1 improvement (MD = 0.63, 95% CI: 0.22, 1.04). For improving FVC, Shengmai injection (SGM) combined with RT showed the greatest therapeutic effect (MD = 0.38, 95% CI: 0.13, 0.61). Moreover, SGM combined with RT revealed the best estimates for response rate (MD = 4.00, 95% CI: 1.34, 13.63). The main adverse events in this study were gastrointestinal reactions and injection site reactions. No serious adverse events were reported. Conclusion. In this network meta-analysis, SGM and CKZ were potential best adjunctive therapies in the treatment of AECOPD.

scholarly journals Single-inhaler Triple vs Single-inhaler Dual Therapy in Patients with Chronic Obstructive Pulmonary Disease: A Meta-analysis of Randomized Control Trials

2021 ◽  
Author(s):  
Huanyu Long ◽  
Hongxuan Xu ◽  
Jean-Paul Janssens ◽  
Yanfei Guo
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Triple Therapy ◽  
Pulmonary Disease ◽  
Risk Ratio ◽  
Meta Analysis ◽  
Dual Therapy ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
All Cause Mortality ◽  
Long Acting

Abstract BACKGROUND: A meta-analysis was performed to compare the efficacy and safety of single-inhaler triple therapy combining long-acting beta2-agonist (LABA), long-acting muscarinic antagonist (LAMA), and inhaled corticosteroids (ICS) versus single-inhaler dual therapy (ICS/LABA and LABA/LAMA) in patients with chronic obstructive pulmonary disease (COPD).METHODS: We used the following search terms in PubMed, MEDLINE (OvidSP), EMBASE and Cochrane Library databases to investigate the effect of single-inhaler triple therapy in COPD. The primary end points were the effect of single-inhaler triple therapy on all-cause mortality, risk of acute exacerbation of COPD (AECOPD), and some safety endpoints, compared with single-inhaler dual therapy. Cochrane Collaboration's tool was used to assess quality of each randomized trial and risk of bias. RESULTS: A total of 25,171 patients suffering from COPD were recruited for the 6 studies. This meta-analysis indicated that single-inhaler triple therapy resulted in a significantly lower rate of all-cause mortality than single-inhaler dual therapy (risk ratio, 0.83; 95% CI 0.71‐0.98). Single-inhaler triple therapy reduced the risk of exacerbation (rate ratio, 0.78; 95% CI 0.73‐0.83), prolonged time to first exacerbation (hazard ratio, 0.86; 95% CI 0.84-0.89), improved trough FEV1 (mean difference, 81.35 ml; 95% CI 45.6–117.06) and St George Respiratory Questionnaire (SGRQ) Score (mean difference, -1.48; 95% CI -1.75–-1.22) vs. single-inhaler dual therapy. Risk of pneumonia was however significantly higher with ICS/LAMA/LABA than with LABA/LAMA (risk ratio, 1.25; 95% CI 1.04‐1.50). CONCLUSIONS: This meta-analysis suggests that single-inhaler triple therapy is effective in reducing the risk of moderate or severe exacerbations and death of any causes in COPD patients, compared with single-inhaler dual therapy. However, risk of pneumonia is higher with ICS/LAMA/LABA combination than with dual therapy of LABA/LAMA.TRIAL REGISTRY: ClinicalTrials.gov; No.: CRD42020186726; URL: www.clinicaltrials.gov.

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