Background and significance Current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend the use of long-acting beta agonists (LABA) plus inhaled corticosteroids (ICS), or long-acting muscarinic antagonists (LAMA) for the treatment of patients with moderate to severe COPD. The combination of LABA+LAMA is recently indicated for COPD patients with severe symptoms; however, its role in reducing exacerbations is less clear.
Methods We performed a meta-analysis of randomised controlled trials that compared efficacy and safety of LABA+LAMA versus LABA+ICS in moderate to severe COPD patients. The primary outcome is the rate of COPD exacerbations. Other outcome measures include improvement in trough FEV1, St. George Respiratory Questionnaire for COPD (SGRQ-C) scores, transition dyspnea index (TDI) scores, rescue medication use and pneumonia risk. Analysis was performed in accordance with the Quality of Reporting of Meta-Analyses (QUORUM) guidelines.
Results A total of 6 RCTs with 3370 patients were included. Over-all exacerbation rates were 21% lower in those treated with LABA+LAMA versus LABA+ICS (RR 0.79, [95% CI: 0.66–0.94]). This effect is more pronounced in patients who had >1 exacerbation per year, showing 25% lower exacerbation rates (RR 0.75 [0.60–0.95]) compared to those with no history of prior exacerbations (RR 0.85 [0.61–1.14]). Patients given Indacaterol+Glycopyrronium also experienced lower rates exacerbation versus LABA+ICS (RR 0.71 [0.57–0.59]) compared to those given Umeclidinium+Vilanterol (RR 1.16 [0.68–2.00]).
There were also statistically significant improvements in FEV1 (mean difference 70 mL [95% CI: 0.07–0.07 Liters]), improvement in SGRQ-C (mean difference −0.92 points [−0.95, −0.90]), improvement in TDI scores (mean difference 0.24 [0.23–0.25]) and decrease in use of rescue medications (mean difference −0.20 puffs/day[−0.21, −0.20]). Pneumonia risk was 41% lower in patients given LABA+LAMA compared LABA+ICS (RR 0.59 [0.43 – 0.80]).