Long-Acting Beta agonists and their relation to increased Asthma Morbidity and Mortality. The FDA Meta-Analysis

10.5580/60b ◽  
2009 ◽  
Vol 7 (1) ◽  
1996 ◽  
Vol 3 (4) ◽  
pp. 261-268 ◽  
Author(s):  
Malcolm R Sears

Many markers of asthma morbidity have shown substantial increases over the past two decades, including family physician visits, use of anti-asthma medications, emergency room visits and hospital admissions. The reported prevalence of diagnosed asthma and of wheezing has increased, especially in children, with accompanying evidence of increased atopy and increased airway responsiveness. Allergen exposure and parental smoking are significant risk factors for childhood wheezing, whereas the influence of outdoor air pollution is uncertain. Increasing use of beta-agonist treatment, which appears to increase the severity of asthma by increasing early and late responses to allergen, may contribute to increased morbidity and mortality, especially if potent beta-agonists are used. Risk factors for asthma mortality include age, smoking, allergy and airway lability, as well as over-reliance on beta-agonists and poor compliance with other aspects of treatment. Following withdrawal of the potent beta-agonist fenoterol in New Zealand, both hospital admissions and mortality from asthma fell abruptly. Continued patient and physician education, with emphasis on avoidance of risk factors and use of appropriate treatment, should reduce morbidity and mortality from asthma in Canada.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Hyun Woo Lee ◽  
Jimyung Park ◽  
Eun Jin Jang ◽  
Chang-Hoon Lee

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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