Illustration of a person holding their head in their hand with the brain highlighted in red and showing signs of ischemic stroke
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Two cheap, safe, and already approved drugs could help treat lacunar stroke—a leading cause of dementia. A study led by the Universities of Edinburgh and Nottingham and the U.K. Dementia Research Institute, found that isosorbide mononitrate and cilostazol, which are currently used to treat other heart and circulatory diseases, can safely improve debilitating outcomes of this type of stroke.

Their findings appear today in JAMA Neurology. The lead author is Joanna M. Wardlaw, MD, of University of Edinburgh.

Sir Nilesh Samani, Medical Director at the British Heart Foundation, said, “These promising findings provide a long-awaited positive step towards the first treatments becoming available for lacunar strokes, offering much needed hope for thousands of people. These findings also open new avenues of research into other conditions related to small vessel disease, such as vascular dementia.”

Lacunar strokes occur when small blood vessels deep within the brain become damaged. This is a common cause of cognitive impairment and dementia. There are currently no effective treatments.

Cilostazol and isosorbide mononitrate are believed to improve the function of the inner lining of blood vessels. As these researchers report, isosorbide mononitrate (ISMN) is a nitric oxide (NO) donor that augments the NO-cyclic guanosine monophosphate phosphodiesterase PDE5-inhibitor pathway. Cilostazol is a PDE3 inhibitor that augments the prostacyclin-cyclic adenosine monophosphate pathway.

The authors write, “Endothelial function depends on both pathways; therefore, both ISMN and cilostazol could improve vascular endothelial function.”

This trial involved 363 people who had experienced a lacunar stroke. They each received standard stroke prevention treatment. But for one year they also took either ISMN or cilostazol individually, both drugs together, or neither.

Participants that took both drugs were nearly 20 percent less likely to have problems with their thinking and memory compared to the group that did not take either drug. They were also more independent and reported a better quality of life.

Taken on their own, ISMN improved thinking and memory skills, and quality of life, while cilostazol improved independence and mood. All these effects were strengthened when the two drugs were taken together.  In addition, those who took isosorbide mononitrate were less likely to have had further strokes at one year than those who did not take the drug.

The team is now planning to test these drugs in a larger four-year clinical trial, which they hope to start by the end of 2023. They are also looking to test whether the drugs are effective in different conditions linked to small vessel disease, such as vascular cognitive impairment and dementia.

Wardlaw, Chair of Applied Neuroimaging at the University of Edinburgh and Foundation Chair at the U.K. Dementia Research Institute, said, “Now we understand more about what is triggering these small vessel strokes to attack the brain, we’ve been able to focus our efforts on treatments that can put a halt to this damage. We need to confirm these results in larger trials before either drug can be recommended as a treatment.”

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