A recent study has found that the buildup of fatty deposits in arteries does not appear to cause lacunar ischaemic stroke, with a different vascular abnormality—enlargement and widening of arteries in the brain—now identified as being strongly linked to lacunar stroke. According to researchers, this new evidence “challenges long-held assumptions” about the causes of lacunar ischaemic strokes, potentially also offering clues as to why widely used preventative treatments—including aspirin and other antiplatelet drugs—are typically less effective in these patients.
These results were presented last week at the 2026 European Stroke Organisation Conference (ESOC; 6–8 May, Maastricht, Netherlands) alongside their publication in the journal Circulation, and are now helping to inform new treatment approaches—including within the LACI-3 trial, which is testing drugs that directly target the brain’s small blood vessels.
To investigate the underlying causes of small vessel disease—and, by extension, lacunar stroke—researchers from the University of Edinburgh (Edinburgh, UK), the UK Dementia Research Institute and other collaborators studied 229 patients who had experienced either lacunar or mild non-lacunar stroke.
Participants underwent clinical and cognitive assessments, along with brain magnetic resonance imaging (MRI) scans at the time of their stroke, and again one year later. These scans allowed researchers to track stroke type, signs of small vessel disease and new areas of brain damage. They compared fatty narrowing of large arteries with widening and elongation of arteries in the brain, and found that narrowing of large arteries was not linked to lacunar stroke nor small vessel disease, despite being seen more commonly in other types of stroke. Additionally, arterial narrowing did not predict new areas of brain injury on follow-up scans.
In contrast, widening of arteries showed strong links to lacunar disease. Patients with this feature were more than four times as likely to have lacunar stroke. Arterial widening was also associated with a greater burden of small vessel disease, faster worsening of brain damage, and a higher risk of developing new ‘silent’ strokes—small areas of brain-tissue damage caused by interrupted blood supply that can occur without obvious symptoms. More than one in four participants developed these silent strokes during the study, despite receiving standard treatments to prevent further strokes.
As such, researchers believe future treatments should instead target the underlying small vessel damage. Trials like LACI-3 are now testing whether existing drugs, including cilostazol and isosorbide mononitrate, can protect the brain, reduce further strokes, and help prevent problems with memory, mobility and dementia after lacunar stroke.
“This study provides strong evidence that lacunar stroke is not caused by fatty blockage of larger arteries, but by disease of the small vessels within the brain itself,” explained Joanna Wardlaw (University of Edinburgh, Edinburgh, UK). “Recognising this distinction is crucial, because it explains why conventional treatments like antiplatelet drugs are not as effective for this type of stroke, and highlights the urgent need to develop new therapies that target the underlying microvascular damage.”
