Background : The place of long-acting β agonist/long-acting muscarinic antagonist (LABA/LAMA) combinations in stable patients with COPD is not well defined. The purpose of this study was to systematically review the efficacy and safety of LABA/LAMA combinations.
Methods : Several databases and manufacturers’ websites were searched for relevant clinical trials. Randomised control trials, at least 12 weeks duration, comparing a LABA/LAMA combination with placebo and/or monotherapy were included. The data were pooled using a network as well as a traditional direct comparison meta-analysis.
Results : Twenty-three trials with a total of 27 172 patients were included in the analysis. LABA/LAMA combinations were associated with a greater improvement in lung function, St. George's Respiratory Questionnaire (SGRQ) score, and Transitional Dyspnoea Index (TDI) than monotherapies. LABA/LAMA combinations were associated with a significantly greater proportion of SGRQ and TDI responders than monotherapies (OR 1.23 (95% credible interval (CrI) 1.06–1.39), OR 1.34 (95% CrI 1.19–1.50) versus LABAs and OR 1.24 (95% CrI 1.11–1.36), OR 1.31 (95% CrI 1.18–1.46) versus LAMAs, respectively) and fewer moderate-to-severe exacerbations compared with LABAs (HR 0.82 (95% CrI 0.73–0.93)), but not when compared with LAMAs (HR 0.92 (95% CrI 0.84–1.00)). There were no statistically significant differences associated with LABA/LAMA combinations compared with monotherapies in safety outcomes as well as in severe exacerbations.
Conclusions : The combination therapy was the most effective strategy in improving lung function, quality of life, symptom scores and moderate-to-severe exacerbation rates, and had similar effects on safety outcomes and severe exacerbations as compared with monotherapies.
Background : While some retrospective studies have suggested that β-blocker use in patients with COPD is associated with a reduction in the frequency of acute exacerbations and lower mortality, there is concern that their use in patients with severe COPD on home oxygen may be harmful.
Methods : Subjects with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2–4 COPD participating in a prospective follow-up of the COPDGene cohort, a multicentre observational cohort of current and former smokers were recruited. Total and severe exacerbation rates were compared between groups categorised by β-blocker use on longitudinal follow-up using negative binomial regression analyses, after adjustment for demographics, airflow obstruction, %emphysema on CT, respiratory medications, presence of coronary artery disease, congestive heart failure and coronary artery calcification, and after adjustment for propensity to prescribe β-blockers.
Results : 3464 subjects were included. During a median of 2.1 years of follow-up, β-blocker use was associated with a significantly lower rate of total (incidence risk ratio (IRR) 0.73, 95% CI 0.60 to 0.90; p=0.003) and severe exacerbations (IRR 0.67, 95% CI 0.48 to 0.93; p=0.016). In those with GOLD stage 3 and 4 and on home oxygen, use of β-blockers was again associated with a reduction in the rate of total (IRR 0.33, 95% CI 0.19 to 0.58; p<0.001) and severe exacerbations (IRR 0.35, 95% CI 0.16 to 0.76; p=0.008). Exacerbation reduction was greatest in GOLD stage B. There was no difference in all-cause mortality with β-blocker use.
Conclusions : β-Blockers are associated with a significant reduction in COPD exacerbations regardless of severity of airflow obstruction. The findings of this study should be tested in a randomised, placebo-controlled trial.