LAUSR

Because there is a solid pharmacological rationale based on positive interactions between long‐acting muscarinic receptor antagonists (LAMAs) and long‐acting β‐agonists (LABAs) for their ability to relax human airway smooth muscle in vitro alongside several randomised controlled trials (RCTs) and real‐world observational studies that support the use of LAMA/LABA fixed‐dose combinations (FDCs) for the treatment of patients with chronic obstructive pulmonary disease (COPD), in this narrative review we discuss the preclinical and clinical proofs supporting the use of LAMA + LABA therapy in COPD and why this therapeutic approach optimises bronchodilation. Robust evidence indicates that all LAMA/LABA FDCs are consistently more effective than LAMA or LABA administered alone in improving lung function, dyspnoea, quality of life and exercise capacity in patients with COPD. However, the ability of dual bronchodilation with FDCs of LAMA/LABA to prevent or reduce the risk of COPD exacerbations remains unclear due to conflicting data from large RCTs, despite several mechanisms explaining why such combinations should be of value in decreasing the frequency of COPD exacerbations. Both LABAs and LAMAs mechanistically can affect the cardiovascular system, but from clinical studies to date, LAMA/LABA FDCs have an acceptable cardiovascular safety profile, at least in the COPD population enrolled in RCTs. Indirect evidence suggests that some FDCs may even exert a protective role against serious cardiovascular adverse events compared to monotherapies. Consequently, several LAMA/LABA FDCs have been developed and approved for clinical use as treatments for patients with COPD. However, to date, there are unfortunately very few head‐to‐head studies comparing the safety and efficacy of different LAMA/LABA FDCs, making it difficult to choose the most appropriate combination, although the use of meta‐analyses has provided some information in this regard.