Association between the cumulative defined daily dose of statins and ischemic stroke recurrence: a cohort study

BACKGROUND: The cumulative defined daily dose (cDDD) enables quantification of statin exposure, balancing therapeutic intensity and patient adherence. However, the relationship between statin cDDD and recurrence risk in ischemic stroke (IS) patients remains unclear. OBJECTIVE: The aim of this study was to investigate the impact of statin cDDD on recurrence risk in IS patients. METHODS: This prospective cohort study enrolled 728 patients with acute ischemic stroke (AIS). After 1 year of follow-up, participants were stratified into four groups (Q1-Q4) according to the quartiles of statin cDDD, and Kaplan-Meier curves were used to estimate the risk of stroke recurrence. The association between cDDD and recurrence risk was examined using restricted cubic spline (RCS) and Cox proportional hazards models, with sensitivity analyses employed to assess population heterogeneity and confirm the robustness of the findings. RESULTS: Kaplan-Meier survival analysis revealed statistically significant differences in recurrence rates across quartiles (P < 0.001). RCS analysis confirmed a nonlinear negative correlation between cDDD and recurrence risk (P for nonlinearity < 0.001). Multivariate Cox regression demonstrated that the recurrence risk in Q4 was 87.7% lower than in Q1. Sensitivity analysis further confirmed that the association between cDDD and IS recurrence risk was independent of antihypertensive or antidiabetic medication use. CONCLUSIONS: Statin cDDD shows a significant nonlinear inverse correlation with stroke recurrence, and exhibits a dose-dependent threshold effect.