Initial Treatment of COPD with LABA-LAMA Versus LAMA: Real-World Comparative Effectiveness and Safety

Respiratory societies now advocate for long-acting beta₂-agonist (LABA) and long-acting muscarinic antagonist (LAMA) combinations (LABA-LAMA) as initial pharmacological treatment of COPD patients with multiple exacerbations or significant symptoms. However, the evidence comes from trials involving treatment-experienced patients. We identified a cohort of newly diagnosed COPD patients, 40 years of age or older, from the UK's Clinical Practice Research Datalink over 2014-2021. Treatment-naïve initiators of single-inhaler LABA-LAMA or LAMA were compared on the incidence of COPD exacerbation and major adverse cardiovascular events (MACE) over one year, after adjustment by propensity score weighting. The cohort included 16,804 initiators of LABA-LAMA and 57,295 of LAMA. The adjusted hazard ratio (HR) of a first moderate or severe exacerbation with LABA-LAMA relative to LAMA was 1.00 (95% confidence interval (CI): 0.96-1.05). This HR was 0.93 (95% CI: 0.86-1.00) among GOLD group E patients, 1.07 (95% CI: 0.99-1.15) among GOLD group B patients, and 0.91 (95% CI: 0.83-0.99) for patients with FEV₁ < 50% predicted. The HR of MACE was 1.13 (95% CI: 1.02-1.25) overall and 1.03 (95% CI: 0.83-1.28) among patients with FEV₁ < 50% predicted. In a real-world clinical practice setting of COPD treatment, initiating therapy with LABA-LAMA may be more effective at exacerbation reduction than LAMA among patients with multiple exacerbations and those with FEV₁<50% predicted. The small increase in MACE risk with LABA-LAMA should be considered when initiating bronchodilator therapy in newly diagnosed COPD, particularly those with FEV₁≥50% predicted. This study supports a targeted approach to initial COPD therapy.