Investigating the treatment of vascular risk with simvastatin in secondary progressive multiple sclerosis: analysis from the MS-STAT2 randomised controlled trial

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ID: 318657
2026
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Abstract
Abstract Vascular comorbidity is associated with more severe disability in multiple sclerosis. However, it is unknown whether treating vascular risk will lead to a disease modifying effect. Given the established role of simvastatin as a modifier of vascular risk, we aimed to investigate whether randomisation to simvastatin could mitigate the relationships between serum cholesterol profiles and disease worsening, compared to placebo, in the MS-STAT2 trial. MS-STAT2 (NCT03387670) recruited 964 patients with secondary progressive multiple sclerosis, who were randomised to simvastatin (80mg) or placebo for 3 years. 246 participants additionally underwent yearly magnetic resonance imaging (MRI). Vascular risks were systematically assessed at trial baseline. In this exploratory analysis, the relationships between cholesterol ratio (total cholesterol/high-density lipoprotein) and longitudinal clinical and MRI outcomes were assessed, comparing simvastatin to placebo groups. At baseline, median (IQR) age was 55 (50-60) years and median cholesterol ratio 3.4 (2.8 to 4.3). 73% were female, and 72% required a walking aid. Higher cholesterol ratio was associated with more severe baseline disability. No longitudinal relationships were observed between cholesterol ratio and clinical or brain atrophy outcomes. However, for each unit increase in cholesterol ratio, T2 lesion volume increased by +2.47% (95% CI: +0.03 to +4.97) from baseline in the placebo group. This relationship was significantly reduced in those randomised to simvastatin (-3.10% [-0.06 to -6.06]). Randomisation to simvastatin appeared to mitigate the relationship between higher cholesterol ratio and longitudinal increases in T2 lesion volume in patients with secondary progressive multiple sclerosis. Further multi-modal interventional studies targeting vascular risk in patients with multiple sclerosis are warranted.
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openalex_W7165727458 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors
Journal Brain communications
Year 2026
DOI
10.1093/braincomms/fcag240
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