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ISC 2023 | Protecting the endothelium as a therapeutic strategy in cerebral small vessel disease

The results of the prospective, randomized, 2×2 factorial Lacunar Intervention Trial 2 (LACI-2) were presented at the International Stroke Conference 2023, demonstrating the promise of cilostazol and isosorbide mononitrate for the treatment of lacunar stroke. These agents exert protective effects on the endothelium and have now been shown to reduce recurrent stroke, cognitive impairment, and dependency in patients with clinical lacunar ischemic stroke in a Phase II setting. Lacunar strokes are caused by the occlusion of small penetrating vessels supplying deep areas of the brain. Joanna Wardlaw, CBE, MD, FRCP, FRSE, FMedSci, University of Edinburgh, Edinburgh, UK, and Philip Bath, DSc, FMedSci, The University of Nottingham, Nottingham University Hospitals NHS Trust, Nottingham, UK, comment on the promise of cilostazol, isosorbide mononitrate, and agents with similar mechanisms of action in lacunar stroke and beyond. As well as confirming the efficacy of these agents in clinical lacunar stroke with the Phase III LACI-3 trial, it is hoped that this approach could be further tested in patients with radiological evidence of lacunar stroke but no clinical symptoms, as well as other forms of small vessel disease, stroke, and neurodegenerative diseases. This interview took place during the International Stroke Conference (ISC) 2023 in Dallas, TX.

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Philip Bath: My team was supported by the British Heart Foundation for this work.
Joana Wardlaw: British Heart Foundation funded LACI-2 with input from the UK Dementia Research Institute (funded by UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK), the Stroke Association and the Alzheimer’s Society; I also hold academic research grants for other research on cerebrovascular disease.