LACunar Intervention Trial-3 (LACI-3): Assessment of safety and efficacy of cilostazol and isosorbide mononitrate to prevent recurrent lacunar stroke and progression of cerebral small vessel disease.

A quarter of all strokes are lacunar strokes—small, deep brain infarcts caused by diseased small blood vessels—and no drug is currently proven to prevent them recurring. This matters because lacunar stroke survivors face a high risk of repeat strokes, cognitive decline, and long-term disability. Existing antiplatelet drugs like aspirin offer limited protection and increase bleeding risk. The LACI-2 trial showed that two repurposed drugs—cilostazol (a platelet inhibitor) and isosorbide mononitrate (a vasodilator)—were safe, well tolerated, and individually appeared to reduce recurrent stroke, improve cognition, and enhance quality of life. The combination seemed to maintain or strengthen these benefits. If LACI-3 confirms these findings, it could provide the first evidence-based drug treatment specifically for lacunar stroke and the underlying small vessel disease. That would change clinical practice for a patient group that currently has no tailored therapy, potentially preventing thousands of repeat strokes and slowing cognitive decline. The drugs are already off-patent and inexpensive, so implementation could be rapid and cost-effective within the NHS.