In Chronic Obstructive Pulmonary Disease (COPD), when do we initiate treatment with a Long-Acting Muscarinic Antagonist (LAMA) versus a Long-Acting Beta-Agonist (LABA)?

From the Guidelines

In COPD, a long-acting muscarinic antagonist (LAMA) is typically started as first-line maintenance therapy for patients with persistent symptoms or exacerbations, while a long-acting beta-agonist (LABA) is generally considered as an alternative first-line option or added as part of combination therapy, as recommended by the 2023 Canadian Thoracic Society guideline on pharmacotherapy in patients with stable COPD 1. The guideline suggests that LAMAs, such as tiotropium, umeclidinium, or glycopyrronium, are preferred initially because they provide superior exacerbation prevention compared to LABAs and offer effective bronchodilation with once-daily dosing. Some key points to consider when deciding between LAMA and LABA include:

• The patient's symptom burden, including shortness of breath, activity limitation, and impaired health status
• The patient's risk of future exacerbations, including the number of moderate or severe exacerbations in the last year
• The patient's spirometry results, including FEV1 percentage
• The presence of concomitant asthma, which may affect the choice of therapy As stated in the 2023 Canadian Thoracic Society guideline, LAMA/LABA single inhaled dual therapy is preferred over ICS/LABA inhaled combination therapy considering the additional improvements in lung function and the lower rates of adverse events such as pneumonia 1. The preference for LAMAs stems from their mechanism of action blocking acetylcholine's bronchoconstricting effect on M3 receptors in airway smooth muscle, while also reducing mucus secretion, which addresses both the bronchospasm and hypersecretion components of COPD. LABAs, such as salmeterol, formoterol, or indacaterol, may be chosen first in patients who have predominant exercise limitation or dyspnea without frequent exacerbations, or in those who experience significant anticholinergic side effects from LAMAs (dry mouth, urinary retention, glaucoma) 1.

From the Research

COPD Treatment Guidelines

The decision to start with a Long-Acting Muscarinic Antagonist (LAMA) versus a Long-Acting Beta-Agonist (LABA) in COPD patients depends on various factors, including symptom severity and exacerbation history.

• According to the study 2, tiotropium (a LAMA) is more effective than salmeterol (a LABA) in preventing exacerbations in patients with moderate-to-very-severe COPD.
• The study 3 suggests that LAMA/LABA combinations can be used as initial maintenance therapy for symptomatic patients with low exacerbation risk and severe breathlessness or patients with severe symptoms who are at risk of exacerbations.

Patient Selection

The choice between LAMA and LABA as initial therapy may depend on individual patient characteristics, such as:

• Symptom severity: Patients with more severe symptoms may benefit from dual bronchodilator therapy (LABA/LAMA) 4.
• Exacerbation history: Patients with a history of exacerbations may benefit from LAMA therapy 2.
• COPD classification: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) report recommends initial pharmacological treatment with a LAMA or a LABA as monotherapy for most patients, or dual bronchodilator therapy (LABA/LAMA) in patients with more severe symptoms 4.

Treatment Efficacy and Safety

• The study 5 found that tiotropium (a LAMA) is safe and efficacious as a long-term, once-daily treatment for COPD, reducing exacerbations and improving lung function.
• The study 6 provides an overview of LAMA/LABA combinations, highlighting their efficacy and safety in COPD management.
• The study 3 found that LAMA/LABA treatment leads to greater improvements in lung function and symptoms than LAMA monotherapy or ICS/LABA treatment, with a similar incidence of adverse events.