Association of statin therapy on acute ischemic stroke patients with atrial fibrillation: insights from a nationwide cohort study

Although statins are well-established in improving outcomes after ischemic stroke, their effectiveness in patients with acute ischemic stroke (AIS) and atrial fibrillation (AF) without conventional indications remains uncertain. This study investigates the association between statin therapy and vascular outcomes in patients with AIS and AF without previously diagnosed atherosclerotic cardiovascular disease (ASCVD). This retrospective, nationwide cohort study utilized the Korean National Health Insurance Service database (2011–2023). Patients aged ≥ 20 years with AIS or transient ischemic attack and concurrent AF were included if they underwent neuroimaging, had no prior statin use at admission, and no documented history of ASCVD. Propensity score matching and inverse probability of treatment weighting (IPTW) were used to adjust for potential confounders. The primary outcome was a composite of all-cause death, ischemic stroke or systemic embolism, intracranial hemorrhage (ICH), and myocardial infarction within 1 year. Hazard ratios (HR) were estimated using Cox regression. Subgroup analyses assessed the association of statin dose (high vs. standard), ezetimibe combination therapy, and statin type. A total of 64,190 patients (mean age; 73.76, male 55.3%) were finally analyzed and categorized into statin users (n = 37,033) and non-users (n = 27,157). In the IPTW analysis, statin-user was associated with lower risk for primary vascular outcomes (HR 0.821 [95% CI 0.808–0.835]), mortality (HR 0.746 [0.729–0.763]), ischemic stroke and systemic embolism (HR 0.904 [0.884–0.925]), and ICH (HR 0.725 [0.660–0.796]) compared to non-users. Neither statin dose, statin type, nor ezetimibe combination was significantly associated with differences in the primary outcome. In patients with AIS and AF without previously diagnosed ASCVD, statin therapy was associated with a lower risk of major vascular events. These findings suggest a potential benefit of statins in this population and highlight the need for confirmation through prospective randomized trials.