Effect of evening vs. morning LAMA administration on risk of ICU admission in COPD patients according to adherence to administration timing: A Sub-Study of LAMA BY NIGHT

<bold>Background:</bold> The RCT LAMA BY NIGHT examined whether the timing of long-acting muscarinic antagonists (LAMA) administration influenced clinical outcomes, finding no effect on COPD exacerbations or mortality but a reduction in ICU admissions in the evening dosing group. This study aimed to evaluate whether the association between timing of LAMA and ICU admissions was modified by adherence to the assigned timing. Methods:This post hoc analysis compared evening vs. morning LAMA in patients with COPD. Adherence was defined as using LAMA at least six days a week at the assigned time. Non-adherence was defined as using LAMA at a different time or <6 days a week. Adherence data were collected via patient self-report. ICU admission risk was compared between groups at 6 and 12 months for both adherent and non-adherent patients. Results:A total of 6,747 patients (67%) were included. In the adherent group, the risk of ICU admission was numerically lower in the evening LAMA group at both 6 months (evening:14 vs. morning:24, RR= 0.77, p=0.55) and at 12 months (evening:29 vs. morning:42, RR=0.97, p=1). Among non-adherent patients, the risk of ICU admission did not differ between groups at 6 months (3 vs. 3, RR=0.38, p=0.45) and 12 months (1 vs. 1, RR=0.27, p=0.90). <bold>Conclusions:</bold> Timing of LAMA did not affect the risk of ICU admission in COPD patients. However, the low event rate limits conclusions regarding adherence’s impact.