Celiprolol may help lower risk of fatal vascular complications in vEDS
First non-European study also shows treatment may offer psychological benefits
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Celiprolol may help lower the risk of fatal vascular complications while also providing psychological reassurance for people with vascular Ehlers-Danlos syndrome (vEDS), according to the first study of the treatment conducted outside Europe.
In the Japanese study, nearly half of the patients experienced no vascular or nonvascular complications during follow-up. Many also reported feeling safer and more confident managing daily life after starting celiprolol.
“This first non-European study on the efficacy of celiprolol therapy supports its general tolerability and beneficial effect in reducing life-threatening vascular complications,” researchers wrote.
The study, “Clinical Outcomes and Patient Experiences With Celiprolol Therapy in Vascular Ehlers–Danlos Syndrome: The First Non-European Cohort,” was published in the American Journal of Medical Genetics.
Celiprolol often used as off-label vEDS treatment
Vascular EDS is a form of Ehlers-Danlos syndrome, a group of genetic disorders that affect the connective tissue, which provides structure to joints, skin, blood vessels, and other tissues. It is usually caused by mutations in the COL3A1 gene, leading to reduced levels of type III collagen, a component of connective tissue. It is marked by fragile blood vessels and easily bruised skin.
Celiprolol, previously known as ACER-002 or Edsivo, is an experimental therapy under development by Zevra Therapeutics for vEDS. Because it aims to reduce pressure in blood vessels at risk of rupture, it is used to treat high blood pressure (hypertension) and is often used as an off-label treatment for vEDS. Zevra was not involved in this study.
European studies have demonstrated that celiprolol is well tolerated and effective in improving survival by reducing vascular events in people with vEDS. However, “outcomes in non-European populations and the therapy’s psychological impact remain unclear.”
Vascular events observed in 11 of 26 participants
To learn more, a research group in Japan retrospectively analyzed data from 26 adults with vEDS ages 20 or older who were treated with celiprolol at a single center between 2000 and 2024. Their mean age was 44.8 years, and most were women (53.8%).
About 39% of patients had a familial history of vascular complications. Most were diagnosed following the onset of vEDS-related symptoms, while three began treatments before any vascular events, based on their family histories.
All patients were treated with celiprolol, initiated at a mean age of 36.9 years, and were followed for about eight years. The majority reached a target dose of 400 mg/day (61.5%), while 27% had their dose increased to 200 mg/day, and 7.7% to 300 mg/day. One patient remained on the 100 mg/day dose.
Overall, 10 patients (38.5%) reported side effects attributed to the treatment, including cough, abnormal heartbeat, fatigue, dizziness, low blood pressure, and fainting. Six patients received additional antihypertensive medications.
Twelve patients (46.2%) experienced no vascular or nonvascular events during follow-up. Vascular events were observed in 11 participants and mainly included artery dissection (a tear in the inner layer of the arterial wall) or rupture. One patient died as a result of a rupture of a liver artery.
Nonvascular events, reported in eight participants, included gastrointestinal perforation and a collapsed lung. Five patients had both vascular and nonvascular events.
There were no significant associations between the occurrence of vascular and nonvascular events and participants’ type of genetic mutation (genotype), celiprolol dosage, or use of other medications.
Further analysis revealed that male sex and younger age at celiprolol initiation tended to be associated with symptomatic vascular events.
Many participants felt celiprolol eased symptoms
Interviews were also conducted with 11 patients to explore changes in patients’ perceptions of their disease after celiprolol initiation and their satisfaction with their current healthcare system.
Many participants felt the treatment eased symptoms, provided emotional reassurance, and promoted a more proactive approach to disease management.
“Although medications had been prescribed in the past, none were evidence-based. I finally found one that is,” one patient said. “When I first learned about the existence of this medicine, I felt like I had something to rely on,” another added.
However, some reported the burden of long-term treatment adherence and side effects.
Regarding the healthcare system, patients identified problems accessing medical institutions, the burden of explaining their condition, concerns about social prejudice, and the uncertainty of emergency care.
“I feel reluctant to visit my doctor because I have to explain everything each time,” a patient said.
They also emphasized the need for more personalized care and a medical environment free from prejudice.
“I want to be seen as an individual, not just as a patient with Ehlers–Danlos syndrome,” another patient added.
According to the researchers, this study shows that “celiprolol therapy may reduce fatal vascular events in vEDS and have a positive psychological impact, though nonfatal vascular complications remain frequent.” This underscores “the need for more effective therapeutic strategies,” they added.
