Do Statins Reduce Risk of Stroke in Patients with MoyaMoya disease?

A receent article published in Stroke and Vascular Neurology sugests that in patients with Moya Moya disease (MMD), statin therapy is associated with a reduced risk of subsequent stroke. The findings indicate statin treatment may be beneficial for patients with MMD.

Moyamoya disease  is a rare cerebrovascular disease characterised by progressive non-atherosclerotic steno-occlusive changes in the terminal portion of the bilateral internal carotid artery (ICA) and formation of abnormal vascular networks. As the disease progresses, patients with MMD are at increased risk of experiencing cerebrovascular complications of ischaemic and haemorrhagic stroke. For patients with MMD with severe haemodynamic impairment and repeated ischaemic symptoms, surgical revascularisation is considered the standard treatment to prevent future stroke but is not applicable to all patients. 

Statins are widely prescribed lipid-lowering drugs shown to reduce the risk for cardiovascular disease, particularly due to atherosclerosis, such as ischaemic stroke or myocardial infarction. Based on extensive evidence, statin therapy is highly recommended as primary and secondary prevention for individuals with established atherosclerotic cardiovascular disease or subjects at high risk of developing atherosclerotic cardiovascular disease. Although MMD is a non-atherosclerotic vasculopathy, statins have multiple pleiotropic and vasculoprotective activities including endothelial protection, vascular remodelling, antithrombotic, anti-inflammatory, immunomodulatory and lipid-lowering effects. Inflammation and immune responses play an important role in the development and progression of MMD. Therefore, statins are considered potential candidates for medical treatment in MMD. 

In this nationwide population-based cohort study conducted Yoo et al from South Korea with 13 373 newly diagnosed patients with MMD,  statin treatment was associated with a lower incidence of stroke. Patients with MMD who received statin treatment were also at lower risk of all-cause mortality. Regardless of a concurrent stroke at the time of MMD diagnosis and revascularisation surgery, statinswere associated with a decreased risk of stroke. 

In patients with MMD, various circulating proinflammatory molecules and angiogenetic factors are involved in the formation of moyamoya vessels by causing endothelial proliferation, intimal thickening, smooth muscle cell migration and matrix accumulation. Therefore, controlling the inflammatory and pathogenic cascade could be a possible target in the treatment of MMD. Experimental and clinical evidence has shown that statins exert various vasculoprotective effects on immunomodulatory, anti-inflammatory and antioxidant properties independent of their LDL-C-lowering effects. Statins increase the bioavailability of nitric oxide, promote re-endothelialisation, reduce oxidative stress and suppress CD40 expression and nuclear factor (NF)-κB activation, which inhibit the inflammatory response. Statins also modulate hypoxia-induced endothelial proliferation, formation of reactive oxygen species and the angiogenesis signalling pathway. 

In the present study, statins were associated with a lower incidence of haemorrhagic stroke in patients with MMD who are at high risk of haemorrhagic stroke due to their vulnerable moyamoya vessels. In addition, haemorrhagic stroke occurred more frequently than ischaemic stroke. When rebleeding occurs in patients with MMD with prior haemorrhagic stroke, the prognosis is very poor. Statin therapy can inhibit the expression of the proinflammatory molecules which  contribute to the reduction of haemorrhagic stroke, a critical complication in patients with MMD. The results of the present study indicate statins may protect against haemorrhagic stroke in patients with MMD, and statins can at least be used relatively safely in patients with MMD at increased risk of haemorrhagic stroke.

Although statins are not commonly used in patients with MMD, statins may be a useful treatment option for the prevention of stroke in patients with MMD. The potential effects of statins demonstrated in this study should be further confirmed in prospective studies, the authors suggest.

Reference

Yoo J, Jeon J, Baik M, et al Association between statin therapy and the risk of stroke in patients with moyamoya disease: a nationwide cohort study Stroke and Vascular Neurology 2023;8

doi: 10.1136/svn-2022-001985