Butylphthalide, a medication derived from celery seed, may Excellerate outcomes after an acute ischemic stroke when given in addition to thrombolysis or endovascular treatment, a new report suggests.
Patients treated with butylphthalide had fewer severe neurologic symptoms and better function 90 days after the stroke compared with those receiving placebo.
Butylphthalide is approved and available for use in China, where the study was conducted. However, the medication hasn't been approved for use by the US Food and Drug Administration.
"Patients who received butylphthalide had less severe neurological symptoms and a better living status at 90 days post stroke compared to those who received the placebo," said co-author Baixue Jia, MD, an attending physician in interventional neuroradiology at the Beijing Tiantan Hospital of Capital Medical University and a faculty member at the China National Clinical Research Center for Neurological Diseases in Beijing. "If the results are confirmed in other trials, this may lead to more options to treat strokes caused by clots."
The study was presented at the American Stroke Association's International Stroke Conference (ISC) 2023.
Studying Stroke Outcomes
The researchers describe butylphthalide as a cerebroprotective drug that was originally extracted from seeds of Apium graveolens. In China, previous studies have shown that the drug has cerebroprotective effects in animal models of ischemia-reperfusion, they noted.
In this randomized, double-blind, placebo-controlled trial, Jia and colleagues evaluated whether treatment with butylphthalide could Excellerate 90-day outcomes for adults with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (tPA), endovascular treatment, or both.
The participants were treated at one of 59 medical centers in China between July 2018 and February 2022. Those who had minimal stroke symptoms on their initial exam, defined as a score of 0–3 on the National Institutes of Health Stroke Scale (NIHSS), or had severe stroke symptoms, defined as having a score of 26 or higher on the NIHSS, were excluded from the study.
Along with an initial revascularization intervention chosen by their physician, participants were randomly selected to receive either butylphthalide or a placebo daily for 90 days. The drug was administered through daily intravenous injections for the first 14 days, after which patients received oral capsules for 76 days.
The research team defined the outcomes as "favorable" if a patient fell into one of the following categories 90 days after the stroke:
an initially mild to moderate stroke (NIHSS, 4–7) and no symptoms after treatment, defined as a score of 0 on the Modified Rankin Scale (mRS), which measures disability and dependence;
an initially moderate to serious stroke (NIHSS, 8–14) and no residual symptoms or mild symptoms that don't impair the ability to perform routine activities of daily living without assistance (mRS, 0–1); or
an initially serious to severe stroke (NIHSS, 15–25) and no remaining symptoms or a slight disability that impairs some activities but allows one to conduct daily living without assistance (mRS, 0–2).
Secondary outcomes included symptomatic intracranial hemorrhage, recurrent stroke, and mortality.
Among the 1216 participants, 607 were assigned to the treatment group, and 609 were assigned to the placebo group. The average age was 66 years, and 68% were men.
Overall, participants in the butylphthalide group were 70% more likely to have a favorable 90-day outcome, as compared with the placebo group. Favorable outcomes occurred in 344 patients (56.7%) in the butylphthalide group, as compared with 268 patients (44%) in the placebo group (odds ratio [OR], 1.70; 95% CI, 1.35 – 2.14; P < .001).
In addition, butylphthalide improved function equally well for the patients who initially received tPA, those who received endovascular treatment, and those who received both tPA and endovascular treatment.
Secondary events, such as recurrent stroke and intracranial hemorrhage, weren't significantly different between the butylphthalide and placebo groups.
Jia and colleagues noted the need to understand how butylphthalide works in the brain. Animal studies have suggested several possible mechanisms, but it remains unclear.
"The next step should be investigating the exact mechanisms of butylphthalide in humans," Jia said.
Additional research should assess the medication in other populations, the authors noted, particularly because the study involved participants who received initial treatment with tPA, endovascular treatment, or both. The results may not be generalizable to stroke patients who receive other treatments or to populations outside of China.
"While these are interesting results, this is only one relatively small study on a fairly select population in China. Butylphthalide, a medication initially compounded from celery seed, is not ready for use in standard stroke treatment," said Daniel Lackland, DrPH, a professor of neurology and director of the Division of Translational Neurosciences and Population Studies at the Medical University of South Carolina.
Lackland, who wasn't involved with the study, is a member of the American Stroke Association's Stroke Council. Although butylphthalide was originally extracted from seeds, he noted, it's not what patients would find commercially available.
"The medication used in this study is not the same as celery seed or celery seed extract supplements," he said. "Stroke survivors should always consult with their neurologist or healthcare professional regarding diet after a stroke."
The study was funded by the National Key Technology Research and Development Program of the Ministry of Science and Technology of the People's Republic of China and Shijiazhuang Pharmaceutical Group dl-3-butylphthalide Pharmaceutical. Several authors are employed with Beijing Tiantan Hospital and the Beijing Institute of Brain Disorders. Lackland reported no relevant financial relationships.
International Stroke Conference (ISC) 2023: Abstract 90. Published February 2, 2023.
Carolyn Crist is a health and medical journalist who reports on the latest studies for Medscape, MDedge, and WebMD.
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