Late Breaking Abstract - Evening Administration of Long-Acting Muscarinic Antagonists in Chronic Obstructive Pulmonary Disease to Prevent Exacerbations

Background: For once daily Long-acting muscarinic antagonists (LAMA) products, morning administration is recommended. Night-time parasympathetic activation combined with the less potent effect of LAMA closer to end of the dosing period suggests greater benefits of evening LAMA-administration.

Aims: To determine whether evening LAMA administration reduces the risk of hospitalization-requiring chronic obstructive pulmonary disease (COPD) exacerbations or all-cause mortality within one year, compared with morning dosing.

Methods: In this randomized controlled, digital platform, pragmatic trial, we used a secure digital mailbox system to invite all Danish COPD patients who used a once-daily LAMA. Danish health registers ensured complete follow-up.

Results: We enrolled 10,011 COPD patients using once-daily LAMA, randomly assigning evening (n=5,028) or morning (n=4,983) administration. In the evening-LAMA group, 245 persons (5%) met the primary outcome compared with 249 persons (5%) in the morning-LAMA group. No difference was found for the primary outcome(P=0.93). Evening LAMA reduced the risk of ICU admission(P=0.0077). There was no difference between groups in the incidence of moderate COPD exacerbation(P=0.52), NIV(P=0.51), or all-cause mortality(P=0.57).

Conclusions: Evening LAMA administration in COPD patients is safe and may be beneficial in COPD-patients at high risk of ICU admission.