Impact of Statin Therapy on the Risk of Stroke Recurrence, Mortality, and Dementia After Ischemic Stroke (ISMARDD...

Ischemic stroke (IS) remains a leading global cause of mortality, recurrence, and long-term disability, with survivors also at risk of post-stroke dementia (PSD) and cognitive impairment (PSCI). The precise impact of statin therapy across different IS populations, including those with cardioembolic/atrial fibrillation (CE/AF) strokes and patients with low-baseline low-density lipoprotein (LDL) cholesterol, remains unclear, as does the influence of statin timing, intensity, type, and solubility.

We conducted the Impact of Statin Therapy on the Risk of Stroke Recurrence, Mortality, and Dementia After Ischemic Stroke (ISMARDD) meta-analysis, synthesizing evidence from 51 studies (n = 521,126), to evaluate the association between post-stroke statin therapy and key outcomes: all-cause mortality, stroke recurrence, cognition, and C-reactive protein (CRP). PSD was defined as new, persistent cognitive decline meeting standard diagnostic criteria, and PSCI as measurable but sub-threshold cognitive deficits. Random-effects models were used, and certainty was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.

Statin therapy significantly reduced all-cause mortality within 3 months (OR 0.32), at 1 year (OR 0.35), and beyond 1 year (OR 0.56). Stroke recurrence was modestly reduced both within 1 year (OR 0.77) and after 1 year (OR 0.76). Statin use was associated with a lower risk of PSD (OR 0.74) but not PSCI overall. Benefits extended to CE/AF-related strokes and patients with low-baseline LDL cholesterol, both showing significantly lower mortality with statin use. Early initiation (<24 h) was linked with reduced recurrence, though effects of statin intensity, type, and solubility were inconsistent. Statins also significantly reduced CRP levels, underscoring anti-inflammatory and pleiotropic mechanisms.

The ISMARDD study demonstrates that statins confer survival benefit and selective cognitive protection (notably reduced PSD risk) after ischemic stroke, with modest recurrence benefit, supporting their broad use in secondary prevention. These findings highlight the need for precision-guided approaches tailored to stroke subtype, pharmacogenomics, and treatment timing to optimize therapeutic outcomes.