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

Abstract 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.