New medicine derived from celery seeds given after clot treatment may improve stroke outcomes

People who had an ischemic stroke (caused by clots) and were treated with a clot-busting drug and/or mechanical removal of the clot and also received butyl phthalide, a drug initially made from celery seeds, experienced neurological symptoms milder with better functioning three months after their stroke, compared with stroke patients who had their clots treated but received a placebo drug, according to preliminary research to be presented at American Stroke’s International Stroke Conference 2023 Association. The meeting, which will take place in Dallas in person and virtually on February 8 -10, 2023, is a first-ever global meeting for researchers and clinicians dedicated to the science of stroke and brain health.

In previous studies in China, butyl phthalide has shown the potential to safely protect and preserve the brain from possible stroke-related damage in animal models of clot-induced strokes. The current study evaluated whether treatment with butyl phthalide can improve outcomes in people who initially received the intravenous clot-busting drug tissue plasminogen activator (tPA) and/or a mechanical clot removal procedure to remove physically the clot plus butylphthalide. In China, butyl phthalide is licensed for use in the treatment of ischemic stroke; however, it is not currently approved by the United States Food and Drug Administration.

“This is the first study showing the benefit of using a drug that protects the brain from damage caused by lack of oxygen to brain tissue. The drug was given to acute ischemic stroke patients who were also receiving treatment to restore blood flow to the brain,” said Baixue Jia, MD, study co-author, attending physician in interventional neuroradiology in the neurology department of Capital Medical University’s Beijing Tiantan Hospital and faculty member at the China National Clinical Research Center for Neurological Diseases, both in Beijing.

The researchers studied 90-day outcomes in 1,216 adults (mean age, 66 years; 68% men) after suffering a stroke initially treated with tPA or mechanical clot-removal therapy. Participants were treated between 2018 and 2022 at one of 59 medical centers in China. People who had minimal stroke symptoms during their initial exam (defined as 0-3 on the National Institutes of Health Stroke Scale, or NIHSS) or had severe stroke symptoms (defined as >26 on the NIHSS) were excluded from this study .

Along with the initial physician-chosen treatment, participants were randomly selected to receive butylphthalide or a similar placebo administered by daily intravenous injection for the first 14 days, followed by 76 days of oral capsules. Patients were randomly assigned to either the butyl phthalide treatment group (607 adults) or the placebo group (609 adults). Neither the patients nor the research team knew which participants were assigned which treatment.

Results were deemed favorable if an individual had the following markers 90 days after the stroke:

• an initially mild to moderate stroke (4-7 on the NIHSS) and no symptoms (0 on the modified Rankin Scale, a scale that measures disability and dependency) after treatment;
• a stroke that was initially moderate to severe (8-14 on the NIHSS) and had no residual symptoms or mild symptoms that did not impair their ability to perform the routine activities of daily living without assistance (0-1 on the disability scale); OR
• an initially severe to severe stroke (15-25 on the NIHSS) had no remaining symptoms or mild disability that impaired some activities but still allowed a person to go about their business without assistance (0-2 on the disability scale).

The study found:

• Participants in the butyl phthalide group were 70 percent more likely to have a favorable outcome at 90 days than in the placebo group.
• Butylphthalide improved function equally well in subgroups of patients who initially received tPA, those who received endovascular therapy, or those who received both tPA and endovascular treatment.
• Secondary events, such as recurrent stroke and intracranial hemorrhage (bleeding in the brain), were not significantly different between the butyl phthalide and placebo groups.

“Patients who received butylphthalide had less severe neurological symptoms and improved life status 90 days post-stroke than those who received the placebo. If the findings are confirmed in other studies, this could lead to more options for treat strokes caused by blood clots,” Jia said.

It is unclear how butyl phthalide works, with animal studies suggesting various possible mechanisms. “The next step should be to investigate the exact mechanisms of butylphthalide in humans,” Jia said.

The study is limited in that it was based on participants who all received initial treatment with intravenous clot-busting drugs or a procedure to remove the clot, or both, so the results may not be generalizable to stroke patients who received other treatments. The results of this study conducted in China may not be generalizable to other populations. Additionally, butyl phthalide is not approved by the FDA for any use in the United States

“Although these are interesting results, this is only a relatively small study in a fairly select population in China. Butylphthalide, a drug originally made from celery seeds, is not ready for use in standard stroke treatment; however, these findings warrant further consideration of the study,” said Daniel T. Lackland, American Stroke Association volunteer expert and EPI and Stroke Council member, Dr.PH, FAHA, professor and director, Division of Neuroscience Translational and Population Studies and the Department of Neurology at the Medical University of South Carolina in Charleston, SC. ​​“The drug used in this study is not the same as celery seed or celery seed supplements. The survivors stroke should always consult their neurologist or healthcare professional regarding diet after a stroke.” Dr. Lackland was not involved in this study.

Co-authors are lead author Anxin Wang, Ph.D.; Xuelei Zhang, MD; Yilong Wang Sr., MD, Ph.D.; and Zhongrong Miao, MD, Ph.D.