Meta-analysis: Anticholinergics, but not beta-agonists, reduce severe exacerbations and respiratory mortality in COPD
ABSTRACT Anticholinergics and beta2-agonists have generally been considered equivalent choices for bronchodilation in chronic obstructive pulmonary disease (COPD).
To assess the safety and efficacy of anticholinergics and beta2-agonists in COPD.
We comprehensively searched electronic databases from 1966 to December 2005, clinical trial websites, and references from selected reviews. We included randomized controlled trials of at least 3 months duration that evaluated anticholinergic or beta2-agonist use compared with placebo or each other in patients with COPD.
We evaluated the relative risk (RR) of exacerbations requiring withdrawal from the trial, severe exacerbations requiring hospitalization, and deaths attributed to a lower respiratory event.
Pooled results from 22 trials with 15,276 participants found that anticholinergic use significantly reduced severe exacerbations (RR 0.67, confidence interval [CI] 0.53 to 0.86) and respiratory deaths (RR 0.27, CI 0.09 to 0.81) compared with placebo. Beta2-agonist use did not affect severe exacerbations (RR 1.08, CI 0.61 to 1.95) but resulted in a significantly increased rate of respiratory deaths (RR 2.47, CI 1.12 to 5.45) compared with placebo. There was a 2-fold increased risk for severe exacerbations associated with beta2-agonists compared with anticholinergics (RR 1.95, CI 1.39 to 2.93). The addition of beta2-agonist to anticholinergic use did not improve any clinical outcomes.
Inhaled anticholinergics significantly reduced severe exacerbations and respiratory deaths in patients with COPD, while beta2-agonists were associated with an increased risk for respiratory deaths. This suggests that anticholinergics should be the bronchodilator of choice in patients with COPD, and beta2-agonists may be associated with worsening of disease control.
Full-textDOI: · Available from: Shelley R Salpeter, Jun 24, 2015
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ABSTRACT: COPD is characterized by progressive airflow obstruction which does not fully reverse to inhaled or oral pharmacotherapy. The management of patients with COPD has taken a totally new direction over the past 20 years, thank to the use of novel therapies aimed to improve and modify the natural history of COPD. Long-acting bronchodilators, including long-acting beta2-agonists (LABAs), were introduced several years ago in order to enhance improvements in lung function, health status related quality of life, and reduce the rate of exacerbations. These effects can be boosted by the combination of LABAs with long-acting anticholinergic, and/or with inhaled corticosteroids. Inhaled LABAs are commonly well tolerated although adverse effects such as tremor and palpitations are occasionally troublesome.International Journal of COPD 02/2008; 3(4):521-9. · 2.73 Impact Factor
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ABSTRACT: Background: Observational pharmacoepidemiological (PE) studies on drug safety have produced discrepant results that may be due to differences in design, conduct and analysis. Purpose: The pharmacoepidemiology work-package (WP2) of the Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium (PROTECT) project aims at developing, testing and disseminating methodological standards for design, conduct and analysis of pharmacoepidemiological studies applicable to different safety issues using different databases across European countries. This article describes the selection of the safety issues and the description of the databases to be systematically studied. Methods: Based on two consensus meetings and a literature search, we selected five drug-adverse event (AE) pairs to be evaluated in different databases. This selection was done according to pre-defined criteria such as regulatory and public health impact, and the potential to investigate a broad range of methodological issues. Results: The selected drug-AE pairs are: 1) inhaled long-acting beta-2 agonists and acute myocardial infarction; 2) antimicrobials and acute liver injury; 3) antidepressants and/or benzodiazepines and hip fracture; 4) anticonvulsants and suicide/suicide attempts; and 5) calcium channel blockers and malignancies. Six European databases, that will be used to evaluate the drug-AE pairs retrospectively, are also described. Conclusion: The selected drug-AE pairs will be evaluated in PE studies using common protocols. Based on consistencies and discrepancies of these studies, a framework for guiding methodological choices will be developed. This will increase the usefulness and reliability of PE studies for benefit-risk assessment and decision-making.11/2013; 9(2). DOI:10.2174/1574884708666131111211802