Efficacy and safety of long-acting muscarinic antagonists in COPD: A meta-analysis and meta-regression with a focus on aging

The increasing global elderly population, projected to reach 20 % of individuals aged 65 and over by 2030, faces significant pulmonary challenges, including chronic obstructive pulmonary disease (COPD). Aging is associated with a natural decline in lung function and structural changes that exacerbate respiratory issues. COPD, characterized by chronic respiratory symptoms and airflow obstruction, presents a unique challenge in older patients due to the accelerated decline in lung function. Acetylcholine plays a pivotal role in airway dynamics through muscarinic acetylcholine receptors, particularly M₃ subtype, which mediates bronchoconstriction. The efficacy of long-acting muscarinic antagonists (LAMA) may differ in older adults, with evidence suggesting that these patients can respond favorably to LAMA treatment. This study utilized meta-analysis and meta-regression to explore the efficacy and safety of LAMA in treating COPD, while considering aging as a potential modifier. A meta-analysis of Phase III randomized controlled trials highlighted significant improvements in trough forced expiratory volume in the 1st second when LAMA were compared to placebo (PCB). Furthermore, the meta-regression revealed a trend suggesting older adults may experience enhanced benefits from LAMA therapy, particularly with once-daily regimens. Safety outcomes, including serious adverse events (SAE), cardiovascular SAE, and mortality, were not modulated by age when comparing LABA to PCB. Overall, these findings support the use of LAMA in elderly COPD patients and underscore the need for tailored treatment strategies to improve clinical outcomes in this vulnerable population.