Transient anticholinergic burden and out-of-hospital cardiac arrest: a case-crossover study

BACKGROUND AND AIMS: Anticholinergic burden has been linked to cardiovascular events and mortality, but its association with out-of-hospital cardiac arrest (OHCA) remains unclear. This study investigated whether transient increases in anticholinergic burden elevate OHCA risk in middle-aged and older populations. METHODS: A nationwide case-crossover, case-time-control, and case-case-time-control study using Taiwan's National Health Insurance Research Database involved 173 974 adults aged ≥40 years who experienced OHCA between 2011 and 2021. The participants were middle-aged (40-64 years) or older (≥65 years). Anticholinergic burden was assessed using established scales and categorized as 0, 1-2, and 3 or more points. Each participant's burden during the hazard period (days -30 to -1 before OHCA) was compared to a randomly selected 30-day reference period (from days -180 to -61). Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Case-crossover analysis showed more patients having higher anticholinergic burden during the hazard period than during the reference period in both age groups. The ORs for OHCA were 1.48 (95% CI: 1.42-1.55) and 1.56 (95% CI: 1.52-1.61) for scores of 1-2, compared with 0, and 2.03 (95% CI: 1.95-2.11) and 2.21 (95% CI: 2.15-2.27) for scores of 3 or more, compared to 0, in the middle-aged and older groups, respectively. Case-time-control and case-case-time-control analyses consistently showed a dose-response relationship, with results confirmed by sensitivity analyses. CONCLUSIONS: Transient increases in anticholinergic burden significantly raise OHCA risk, particularly among individuals with higher burden levels.