scholarly journals Comparisons of Efficacy and Safety between Triple (Inhaled Corticosteroid/Long-Acting Muscarinic Antagonist/Long-Acting Beta-Agonist) Therapies in Chronic Obstructive Pulmonary Disease: Systematic Review and Bayesian Network Meta-Analysis

Respiration ◽  
2021 ◽  
pp. 1-13
Author(s):  
Hyun Woo Lee ◽  
Hyung Jun Kim ◽  
Eun Jin Jang ◽  
Chang-Hoon Lee
Keyword(s):  
Cardiovascular Events ◽  
Meta Analysis ◽  
Beta Agonist ◽  
Chronic Obstructive ◽  
Inhaled Corticosteroid ◽  
Obstructive Pulmonary Disease ◽  
All Cause Mortality ◽  
Long Acting ◽  
Severe Copd ◽  
Related Mortality

<b><i>Background:</i></b> Various combinations of inhaled corticosteroid (ICS), long-acting muscarinic antagonist (LAMA), and long-acting beta-agonist (LABA) have been used as triple therapy for stable chronic obstructive pulmonary disease (COPD). <b><i>Objective:</i></b> Our study was conducted to answer whether there were significant differences among various combinations in efficacy, for reducing exacerbation or mortality, and in safety, for increasing cardiovascular events or pneumonia. <b><i>Method:</i></b> We searched parallel-group randomized controlled trials (RCTs) comparing ICS/LAMA/LABA with other inhaled drugs in patients with stable COPD for at least 12 weeks in PubMed, EMBASE, the Cochrane Library, and clinical trial registries from inception to December 31, 2019. We conducted a network meta-analysis with Bayesian statistics using a random-effects model with heterogeneous variance structure (PROSPERO, CRD42019126757). <b><i>Results:</i></b> Nine different combinations of ICS/LAMA/LABA were identified in 21 RCTs containing 29,892 patients with moderate to very severe COPD. We could not find any significant evidence suggesting a better treatment for reducing total exacerbations or all-cause mortality among ICS/LAMA/LABA combinations. There were also no significant differences in moderate to severe exacerbation, COPD-related mortality, or cardiovascular disease-related mortality among ICS/LAMA/LABA combinations, and the risk of major adverse cardiovascular events was not different. A significantly lower risk of pneumonia was found in fluticasone propionate (FP)/glycopyrrolate/salmeterol (SAL) than FP/tiotropium/SAL {median odds ratio [OR] (95% credible interval [CrI]) = 0 [0–0.72]} and FP/umeclidinium/SAL {median OR (95% Crl) = 0 [0–0.97]}. <b><i>Conclusion:</i></b> There were no significant differences in clinical outcomes, including acute exacerbation and all-cause mortality among various ICS/LAMA/LABA combinations in patients with moderate to very severe COPD.

scholarly journals Major comorbidities lead to the risk of adverse cardiovascular events in chronic obstructive pulmonary disease patients using inhaled long-acting bronchodilators: a case-control study

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yen-Fu Chen ◽  
Yi-Ching Cheng ◽  
Chien-Hong Chou ◽  
Chung-Yu Chen ◽  
Chong-Jen Yu
Keyword(s):  
Cardiovascular Events ◽  
Case Control Study ◽  
Case Control ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
History Of ◽  
Long Acting ◽  
Control Study ◽  
Related Mortality

Abstract Background While inhaled bronchodilators reduce symptoms and acute exacerbations of chronic obstructive pulmonary disease (COPD), their use is associated with increased cardiovascular events in some studies. This study investigates the risk of adverse events associated with the use of inhaled bronchodilators in COPD patients with multimorbidity. Methods A case-control study was conducted between January 2015 and December 2017, and patients with spirometry-confirmed diagnosis of COPD (N = 1565) using inhaled long-acting bronchodilators were enrolled. Medical records were reviewed and clinical data, including age, gender, smoking status, major comorbidities, lung function stage, history of exacerbations, bronchodilator regimens, and treatment duration were analyzed. Major adverse cardiovascular events occurring during long-acting bronchodilator use were recorded. Results The most common comorbidities were cardiovascular disease (CVD) (53.6%) and chronic kidney disease (CKD) (25.8%). We observed that CVD (odds ratio [OR], 5.77), CKD (OR, 2.02) and history of frequent exacerbations (OR, 2.37) were independent risk factors for cardiovascular events, regardless of the type of bronchodilators use. Moreover, COPD patients with both CKD and CVD had higher risk (6.32-fold) of adverse cardiovascular effects than those with neither comorbidity. Eighty-seven of 1565 (5.56%) COPD patients died during this study period. Of them, 21.8% (19/87) were cardiovascular-related and 73.6% (64/87) patients were respiratory-related mortality. Among COPD patients using long-acting bronchodilators, CKD was the only risk factor to predict cardiovascular events and cardiovascular-related mortality (OR, 4.87; 95% confidence interval [CI], 1.75–13.55]. Conclusions COPD patients had higher risk of cardiovascular events were associated with their CVD and/or CKD comorbidities and history of frequent exacerbations, rather than associated with their use of inhaled bronchodilators.

scholarly journals Comparisons of exacerbations and mortality among LAMA/LABA combinations in stable chronic obstructive pulmonary disease: systematic review and Bayesian network meta-analysis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Hyun Woo Lee ◽  
Jimyung Park ◽  
Eun Jin Jang ◽  
Chang-Hoon Lee
Keyword(s):  
Bayesian Network ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Major Adverse Cardiovascular Events ◽  
Chronic Obstructive ◽  
Level Of Evidence ◽  
Obstructive Pulmonary Disease ◽  
Beta Agonists ◽  
All Cause Mortality ◽  
Long Acting

Abstract Background Only few randomized controlled trials (RCTs) for head-to-head comparison have been conducted between various combinations of long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs). Our study was conducted to compare acute exacerbation and all-cause mortality among different LAMA/LABA regimens using Bayesian network meta-analysis (NMA). Methods We searched Medline, EMBASE, and the Cochrane library (search date: July 1, 2019). We included parallel-group RCTs comparing LAMA/LABA combinations with other inhaled drugs in the stable COPD for ≥ 48 weeks. Two different network geometries were used. The geometry of network (A) had nodes of individual drugs or their combination, while that of network (B) combined all other treatments except LAMA/LABA into each drug class. This study was prospectively registered in PROSPERO; CRD42019126753. Results We included 16 RCTs involving a total of 39,065 patients with stable COPD. Six combinations of LAMA/LABA were identified: tiotropium/salmeterol, glycopyrrolate/indacaterol, umeclidinium/vilanterol, tiotropium/olodaterol, aclidinium/formoterol, and glycopyrrolate/formoterol. We found that umeclidinium/vilanterol was associated with a lower risk of total exacerbations than other LAMA/LABAs in the NMA using network (A) (level of evidence: low or moderate). However, the significant differences were not present in the NMA of network (B). There were no significant differences among the LAMA/LABA combinations in terms of the number of moderate to severe exacerbations, all-cause mortality, major adverse cardiovascular events, or pneumonia. Conclusions The present NMA including all available RCTs provided that there is no strong evidence suggesting different benefits among LAMA/LABAs in patients with stable COPD who have been followed up for 48 weeks or more. Trial registration: This study was prospectively registered in PROSPERO; CRD42019126753.

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