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 ◽  
...  

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.

2020 ◽  
Vol 54 (12) ◽  
pp. 1232-1242
Author(s):  
Melissa Lipari ◽  
Pramodini B. Kale-Pradhan ◽  
Sheila M. Wilhelm

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.


2020 ◽  
Vol 14 ◽  
pp. 175346662093719
Author(s):  
Ching-Yi Chen ◽  
Wang-Chun Chen ◽  
Chi-Hsien Huang ◽  
Yi-Ping Hsiang ◽  
Chau-Chyun Sheu ◽  
...  

Background: Long-acting muscarinic antagonist (LAMA) monotherapy is recommended for chronic obstructive pulmonary disease (COPD) patients with high risk of exacerbations. It is unclear whether long-acting β2-agonist (LABA)/LAMA fixed-dose combinations (FDCs) are more effective than LAMAs alone in preventing exacerbations. The aim of this study was to systematically review the literature to investigate whether LABA/LAMA FDCs are more effective than LAMA monotherapy in preventing exacerbations. Methods: We searched several databases and manufacturers’ websites to identify relevant randomized clinical trials comparing LABA/LAMA FDC treatment with LAMAs alone ⩾24 weeks. Outcomes of interest were time to first exacerbation and rates of moderate to severe, severe and all exacerbations. Results: We included 10 trials in 9 articles from 2013 to 2018 with a total of 19,369 patients for analysis in this study. Compared with LAMA monotherapy, LABA/LAMA FDCs demonstrated similar efficacy in terms of time to first exacerbation [hazard ratio, 0.96; 95% confidence interval (CI) 0.79–1.18; p = 0.71], moderate to severe exacerbations [risk ratio (RR), 0.96; 95% CI 0.90–1.03; p = 0.28], severe exacerbations (RR, 0.92; 95% CI 0.81–1.03; p = 0.15), and a marginal superiority in terms of all exacerbations (RR, 0.92; 95% CI 0.86–1.00; p = 0.04). The incidence of all exacerbation events was lower in the LABA/LAMA FDC group for the COPD patients with a history of previous exacerbations and those with a longer treatment period (52–64 weeks). Conclusion: This study provides evidence that LABA/LAMA FDCs are marginally superior in the prevention of all exacerbations compared with LAMA monotherapy in patients with COPD. The reviews of this paper are available via the supplemental material section.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
David Miller ◽  
Soniya Vaidya ◽  
Juergen Jauernig ◽  
Brian Ethell ◽  
Kristina Wagner ◽  
...  

Abstract Background Indacaterol maleate delivered with the Breezhaler® inhalation device is a long-acting β2-agonist approved for chronic obstructive pulmonary disease. In the development of a once daily, inhaled fixed dose combination (FDC) of indacaterol, glycopyrronium bromide (a long-acting muscarinic antagonist), and mometasone furoate (an inhaled corticosteroid [ICS]) for the treatment of patients with asthma, the acetate salt of indacaterol is used instead of the maleate salt. Here, we investigated the lung function, pharmacokinetics (PK) and safety of indacaterol maleate 150 μg once daily (o.d.) and indacaterol acetate 150 μg o.d. in comparison with placebo. Methods This was a randomised, double-blind, three-period crossover study (ClinicalTrials.gov identifier, NCT03257995) in patients with asthma on background ICS therapy. Patients with percent predicted pre-bronchodilator forced expiratory volume per second (FEV1) ≥50% and ≤ 90% were included in the study. Patients received indacaterol maleate 150 μg o.d., indacaterol acetate 150 μg o.d., or placebo on top of stable background ICS in randomised sequence. Trough FEV1 was assessed after 14 days of treatment. PK of indacaterol salts were assessed at steady state after 14 days of treatment; peak expiratory flow (PEF) rate and rescue medication use were collected with a combined PEF-meter/electronic diary throughout the study. Results Of the 54 adult patients (median age of 48 years), 51 patients completed the study. Both indacaterol salts demonstrated statistically significant improvements in trough FEV1 of 186 mL (maleate) and 146 mL (acetate) compared with placebo (both P < 0.001). FEV1 AUC0-4h improved by 248 mL (maleate) and 245 mL (acetate), and PEF by 33 L/min (maleate) and 30.8 L/min (acetate) versus placebo. Systemic exposure of indacaterol (AUC0-24h,ss and Cmax,ss on Day 14) was comparable after administration of both salt forms. Both salt forms demonstrated a good safety profile and were well tolerated, with a difference in the reporting frequency of AEs of coughing (maleate, 23.5%; acetate, 0%). Conclusions In patients with asthma, indacaterol maleate and acetate elicited comparable and significant improvements in lung function compared with placebo and achieved comparable systemic exposure. Both indacaterol salts were safe and well tolerated. Trial registration ClinicalTrials.gov NCT03257995 June 06, 2017


2021 ◽  
pp. jim-2021-001931
Author(s):  
Chuchu Zhang ◽  
Meng Zhang ◽  
Yalei Wang ◽  
Huaiyu Xiong ◽  
Qiangru Huang ◽  
...  

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.


PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255545
Author(s):  
Yixuan Jiang ◽  
Hao Hu ◽  
Siu-wai Leung

Introduction 2021 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Reports recommends that patients with clinically significant symptoms and exacerbations of chronic obstructive pulmonary disease (COPD) should escalate to triple therapy, a combined use of inhaled corticosteroids (ICS), long-acting muscarinic antagonists (LAMA) and long-acting b2-agonists (LABA)(ICS/LAMA/LABA). Triple therapy in fixed-dose combinations (FDCs), i.e., combining ICS, LABA with LAMA and administrating by a single inhalation device, has appeared in recent years. This study aims to compare the efficacy of triple therapy in FDCs in treating patients with moderate to severe COPD. Methods and analyses Literature search will be conducted on PubMed, Embase and Web of science, according to pre-specified and corresponding search strategies, for relevant reports published since the inception dates of the databases. Randomised controlled trials (RCT) which compared the triple therapy in FDCs with other pharmacological therapies will be included. The Cochrane risk of bias assessment tool (RoB 2) will be used to assess the RCT quality. The outcomes will be analyzed as rate ratios and mean differences under a random-effects model in a frequentist network meta-analysis (NMA). Additional statistical analyses including subgroup analysis, sensitivity analysis, and publication bias analysis will be performed to assess the evidential heterogeneity and robustness. The strength of evidence from the NMA will be evaluated with the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) methods. Ethics and dissemination No ethics approval is required as this systematic review and network meta-analysis do not collect confidential personal data and do not carry out interventions in treating patients. Protocol registration number CRD42021240823.


2020 ◽  
Vol 45 (6) ◽  
pp. 589-597
Author(s):  
BGS Casado ◽  
EP Pellizzer ◽  
JR Souto Maior ◽  
CAA Lemos ◽  
BCE Vasconcelos ◽  
...  

Clinical Relevance The use of laser light during bleaching will not reduce the incidence or severity of sensitivity and will not increase the degree of color change compared with nonlaser light sources. SUMMARY Objective: To evaluate whether the use of laser during in-office bleaching promotes a reduction in dental sensitivity after bleaching compared with other light sources. Methods: The present review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and is registered with PROSPERO (CDR42018096591). Searches were conducted in the PubMed/Medline, Web of Science, and Cochrane Library databases for relevant articles published up to August 2018. Only randomized clinical trials among adults that compared the use of laser during in-office whitening and other light sources were considered eligible. Results: After analysis of the texts retrieved during the database search, six articles met the eligibility criteria and were selected for the present review. For the outcome dental sensitivity, no significant difference was found favoring any type of light either for intensity (mean difference [MD]: −1.60; confidence interval [CI]: −3.42 to 0.22; p=0.09) or incidence (MD: 1.00; CI: 0.755 to 1.33; p=1.00). Regarding change in tooth color, no significant differences were found between the use of the laser and other light sources (MD: −2.22; CI: −6.36 to 1.93; p=0.29). Conclusions: Within the limitations of the present study, laser exerts no influence on tooth sensitivity compared with other light sources when used during in-office bleaching. The included studies demonstrated that laser use during in-office bleaching may have no influence on tooth color change.


BMC Surgery ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Stefano Granieri ◽  
Francesco Sessa ◽  
Alessandro Bonomi ◽  
Sissi Paleino ◽  
Federica Bruno ◽  
...  

Abstract Background Entero-colovesical fistula is a rare complication of various benign and malignant diseases. The diagnosis is prominently based on clinical symptoms; imaging studies are necessary not only to confirm the presence of the fistula, but more importantly to demonstrate the extent and the nature of the fistula. There is still a lack of consensus regarding the if, when and how to repair the fistula. The aim of the study is to review the different surgical treatment options, focus on surgical indications, and explore cumulative recurrence, morbidity, and mortality rates of entero-vesical and colo-vesical fistula patients. Methods A systematic review of the literature was conducted according to PRISMA guidelines. Random effects meta-analyses of proportions were developed to assess primary and secondary endpoints. I2 statistic and Cochran’s Q test were computed to assess inter-studies’ heterogeneity. Results Twenty-two studies were included in the analysis with a total of 861 patients. Meta-analyses of proportions pointed out 5, 22.2, and 4.9% rates for recurrence, complications, and mortality respectively. A single-stage procedure was performed in 75.5% of the cases, whereas a multi-stage operation in 15.5% of patients. Palliative surgery was performed in 6.2% of the cases. In 2.3% of the cases, the surgical procedure was not specified. Simple and advanced repair of the bladder was performed in 84.3% and 15.6% of the cases respectively. Conclusions Although burdened by a non-negligible rate of complications, surgical repair of entero-colovesical fistula leads to excellent results in terms of primary healing. Our review offers opportunities for significant further research in this field. Level of Evidence Level III according to ELIS (SR/MA with up to two negative criteria).


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yoko Azuma ◽  
Atsushi Sano ◽  
Takashi Sakai ◽  
Satoshi Koezuka ◽  
Hajime Otsuka ◽  
...  

Abstract Background Chronic obstructive pulmonary disease (COPD) is an important risk factor for postoperative complications and mortality. To determine the effects of perioperative combination therapy, using a long-acting muscarinic antagonist (LAMA) and a long-acting β2 agonist (LABA), on preoperative lung function, postoperative morbidity and mortality, and long-term outcome in COPD patients. Methods Between January 2005 and October 2019, 130 consecutive patients with newly diagnosed COPD underwent surgery for lung cancer. We conducted a retrospective review of their medical record to evaluate that LAMA/LABA might be an optimal regimen for patients with COPD undergoing surgery for lung cancer. All patients were received perioperative rehabilitation and divided into 3 groups according to the type of perioperative inhaled therapy and management: LAMA/LABA (n = 64), LAMA (n = 23) and rehabilitation only (no bronchodilator) (n = 43). We conducted a retrospective review of their medical records. Results Patients who received preoperative LAMA/LABA therapy showed significant improvement in lung function before surgery (p < 0.001 for both forced expiratory volume in 1 s (FEV1) and percentage of predicted forced expiratory volume in 1 s (FEV1%pred). Compared with patients who received preoperative LAMA therapy, patients with LAMA/LABA therapy had significantly improved lung function (ΔFEV1, LAMA/LABA 223.1 mL vs. LAMA 130.0 mL, ΔFEV1%pred, LAMA/LABA 10.8% vs. LAMA 6.8%; both p < 0.05). Postoperative complications were lower frequent in the LAMA/LABA group than in the LAMA group (p = 0.007). In patients with moderate to severe air flow limitation (n = 61), those who received LAMA/LABA therapy had significantly longer overall survival and disease-free survival compared with the LAMA (p = 0.049, p = 0.026) and rehabilitation-only groups (p = 0.001, p < 0.001). Perioperative LAMA/LABA therapy was also associated with lower recurrence rates (vs. LAMA p = 0.006, vs. rehabilitation-only p = 0.008). Conclusions We believe this treatment combination is optimal for patients with lung cancer and COPD.


2021 ◽  
Vol 10 (2) ◽  
pp. 269
Author(s):  
Elisabetta Zinellu ◽  
Alessandro G. Fois ◽  
Elisabetta Sotgiu ◽  
Sabrina Mellino ◽  
Arduino A. Mangoni ◽  
...  

Background: Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by chronic airway inflammation and lung parenchyma damage. Systemic inflammation and oxidative stress also play a role in the pathogenesis of COPD. Serum albumin is a negative acute-phase protein with antioxidant effects and an important marker of malnutrition. The aim of this meta-analysis was to investigate differences in serum albumin concentrations between patients with stable COPD and non-COPD subjects. Methods: A systematic search was conducted, using the terms “albumin” and “chronic obstructive pulmonary disease” or “COPD”, in the electronic databases PubMed and Web of Science, from inception to May 2020. Results: Twenty-six studies were identified on a total of 2554 COPD patients and 2055 non-COPD controls. Pooled results showed that serum albumin concentrations were significantly lower in COPD patients (standard mean difference, SMD = −0.50, 95% CI −0.67 to −0.32; p < 0.001). No significant differences were observed in SMD of serum albumin concentrations between COPD patients with forced expiratory volume in the 1st second (FEV1) < 50% and those with FEV1 > 50%. Conclusions: Our systematic review and meta-analysis showed that serum albumin concentrations are significantly lower in patients with stable COPD compared to non-COPD controls. This supports the presence of a deficit in systemic anti-inflammatory and antioxidant defense mechanisms in COPD.


2014 ◽  
Vol 45 (2) ◽  
pp. 231-246 ◽  
Author(s):  
A. van Straten ◽  
J. Hill ◽  
D. A. Richards ◽  
P. Cuijpers

BackgroundIn stepped care models patients typically start with a low-intensity evidence-based treatment. Progress is monitored systematically and those patients who do not respond adequately step up to a subsequent treatment of higher intensity. Despite the fact that many guidelines have endorsed this stepped care principle it is not clear if stepped care really delivers similar or better patient outcomes against lower costs compared with other systems. We performed a systematic review and meta-analysis of all randomized trials on stepped care for depression.MethodWe carried out a comprehensive literature search. Selection of studies, evaluation of study quality and extraction of data were performed independently by two authors.ResultsA total of 14 studies were included and 10 were used in the meta-analyses (4580 patients). All studies used screening to identify possible patients and care as usual as a comparator. Study quality was relatively high. Stepped care had a moderate effect on depression (pooled 6-month between-group effect size Cohen'sdwas 0.34; 95% confidence interval 0.20–0.48). The stepped care interventions varied greatly in number and duration of treatment steps, treatments offered, professionals involved, and criteria to step up.ConclusionsThere is currently only limited evidence to suggest that stepped care should be the dominant model of treatment organization. Evidence on (cost-) effectiveness compared with high-intensity psychological therapy alone, as well as with matched care, is required.


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