Association between cholinesterase inhibitor use and reduced mortality in patients with malignant arrhythmias: a retrospective cohort study

Malignant ventricular arrhythmias (ventricular tachycardia, flutter, or fibrillation; VT/VF) carry a high mortality risk in critically ill patients. Autonomic imbalance contributes to arrhythmogenesis, yet whether enhancing cholinergic tone with cholinesterase inhibitors (ChEi) improves survival remains unknown. In this retrospective cohort study, adult patients with VT/VF were identified. The principal exposure was ChEi use during ICU stay. The outcome was 1-year and ICU mortality. Association was assessed using Kaplan–Meier analysis, multivariable Cox and modified Poisson regression, with robustness verified by propensity‑score matching (PSM), overlap weighting (OW), time‑dependent Cox modeling, and E‑value calculation. β blockers were stratified by blood-brain‑barrier penetration (BBBp), and a benefit‑based algorithm quantified individualized treatment effects. Among 2,450 patients, 276 (11.3%) received a ChEi. ChEi use was associated with lower 1-year mortality (HR 0.56, 95% CI 0.41–0.75; E‑value 2.97), with consistent estimates across sensitivity analyses (PSM HR 0.62; OW HR 0.64; time‑dependent HR 0.61). High‑BBBp β blockers conferred greater survival benefit than low-medium‑BBBp agents (HR 0.41), and combining ChEi with high‑BBBp β blockers yielded the greatest reduction (HR 0.21). The benefit‑based calculator demonstrated treatment‑effect heterogeneity with a monotonous increase in HR of 1.67, 0.55, 0.47, and 0.24 in patients’ subgroups with benefit scores rising. The calculator was deployed online at https://wishtang.shinyapps.io/ChEi-in-VT-VF/ . ChEi use was associated with decreased mortality in patients with VT/VF, particularly when combined with high‑BBBp β blockers, supporting autonomic rebalancing as a potential therapeutic strategy.