A major international trial suggests an experimental anti-clotting drug may lower the risk of repeat strokes without the dangerous bleeding complications tied to many current treatments.
For decades, stroke specialists have faced a frustrating tradeoff: stronger anti-clotting drugs can reduce the risk of another stroke, but they also raise the danger of serious bleeding. Now, a massive international clinical trial suggests an experimental medication called asundexian may finally help break that pattern.
Researchers found the drug lowered the risk of recurrent stroke in patients who had recently experienced a non-cardioembolic stroke or transient ischemic attack (TIA) — a temporary blockage of blood flow to the brain — without increasing major bleeding, one of the most feared complications of current stroke-prevention therapies.
A broader test of stroke prevention
The OCEANIC-STROKE trial enrolled 12,327 adults in 37 countries within 72 hours of a stroke or high-risk TIA caused by clots forming outside the heart. Participants received either asundexian or a placebo alongside standard antiplatelet therapy, allowing researchers to evaluate whether the drug could offer safer, more effective long-term protection against future strokes.
At present, care after these events usually depends on antiplatelet medicines, a type of anti-clotting treatment that offers only limited risk reduction and can raise bleeding risk when used together or over the long term.
Results from the OCEANIC-STROKE trial appeared in The New England Journal of Medicine (NEJM).
“This is something researchers have been working toward for decades,” said Mike Sharma, principal investigator of the study and a senior scientist at the Population Health Research Institute (PHRI), a joint institute of McMaster University and Hamilton Health Sciences. “Asundexian reduced the occurrence of a stroke by 26 percent, and this benefit was consistent across patients of different ages, sexes, stroke severity, and stroke causes, without increasing major bleeding or other serious side effects.”
Stroke risk fell without bleeding
In the trial, participants were assigned at random to take either asundexian (50 mg once daily) or a placebo, along with standard antiplatelet treatment such as aspirin. Participants had an average age of 68 years, with 25 percent older than 75 and 33 percent women. Most participants (95 percent) had a non-cardiometabolic stroke, while the rest had a high-risk TIA. Non-cardioembolic strokes are common and
make up most ischemic strokes (clot-related strokes), and the trial included a broad sample of people affected by them.
Follow-up visits took place at one month, three months, and then every three months after that to monitor outcomes. Researchers found:
- 6.2 percent of patients taking asundexian had another ischemic stroke, compared with 8.4 percent of those taking placebo, corresponding to a 26 percent reduction in this outcome.
- 9.2 percent had a major cardiovascular event (stroke, heart attack, or cardiovascular death), compared with 11.1 percent on placebo (17 percent reduction).
- Disabling or fatal strokes occurred in 2.1 percent of patients taking asundexian versus three percent in the placebo group (31 percent reduction).
- Patients who received asundexian did not show an increase in bleeding.
“Until now, reducing stroke risk has often been associated with higher bleeding risk. These findings give us hope for a safer way to prevent recurrent strokes,” said Ashkan Shoamanesh, co-principal investigator of the study and PHRI senior scientist. “That’s something physicians, patients, and families have been waiting for.”
Factor XIa gains clinical ground
Asundexian is designed to act differently from existing anti-clotting medicines. It blocks Factor XIa, a protein that helps drive dangerous clot formation but has only a limited role in the body’s normal ability to stop bleeding. By targeting Factor XIa, asundexian was intended to reduce harmful clots while leaving natural bleeding control largely intact, and the OCEANIC-STROKE results now support this newer approach to anti-clotting treatment.
OCEANIC-STROKE is the first completed Phase 3 trial of a Factor XIa inhibitor for preventing a second stroke. Earlier attempts to study long-term secondary stroke prevention have not succeeded because treatments failed to work well enough, caused more bleeding, or both.
“This trial marks a major step toward safer and more effective long-term treatment for stroke prevention,” added Sharma. “It was completed with remarkable scale and efficiency right here in Canada through our global research network.”
Reference: “Asundexian for Secondary Stroke Prevention” by Mukul Sharma, Qiang Dong, Teruyuki Hirano, Scott E. Kasner, Jeffrey L. Saver, Jaime Masjuan, Andrew M. Demchuk, Charlotte Cordonnier, Daniel Bereczki, Georgios Tsivgoulis, Roland Veltkamp, Ivan Staikov, Hee-Joon Bae, Bruce C.V. Campbell, Andrea Zini, I-Hui Lee, Martin Kovar, Robert Mikulik, Robin Lemmens, José M. Ferro, Thompson Robinson, Hanne Christensen, Serefnur Ozturk, Ronen R. Leker, Peter Turcani, Agnieszka Slowik, Pablo Amaya, Fan Kee Hoo, Gian Marco De Marchis, Michael Knoflach, P.N. Sylaja, Jukka Putaala, Jonathan M. Coutinho, H. Bart van der Worp, Evija Miglane, Vaidas Matijošaitis, Arne G. Lindgren, Gisele Sampaio Silva, Else Charlotte Sandset, Saule T. Turuspekova, Pierre Amarenco, Kevin N. Sheth, Eric E. Smith, John W. Eikelboom, Raed A. Joundi, Karleen Schulze, Lizhen Xu, Laura Heenan, Pablo Colorado, Lars Keller, Eva Muehlhofer, Christoph Neumann, Hardi Mundl and Ashkan Shoamanesh, 15 April 2026, New England Journal of Medicine.
DOI: 10.1056/NEJMoa2513880
The study was sponsored by Bayer AG.
Disclosure: Asundexian is still under regulatory review and is not yet approved for clinical use.
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