Asundexian cut stroke risk without raising bleeding risk in a large international trial in people treated after stroke or mini-stroke.
The study involved 12,327 adults from 37 countries who were enrolled within 72 hours of a non-cardioembolic stroke, caused by a clot forming outside the heart, or a transient ischaemic attack, a temporary blockage of blood flow to the brain.
The study assessed the safety and effectiveness of asundexian in preventing another stroke in these patients.
At present, preventing another stroke in these situations relies mainly on antiplatelet medicines, which reduce risk only modestly and can increase bleeding when combined or used long term.
Mike Sharma isprincipal investigator of the study and a senior scientist at the Population Health Research Institute, a joint institute of McMaster University and Hamilton Health Sciences.
He said: “This is something researchers have been working toward for decades.
“Asundexian reduced the occurrence of a stroke by 26 per cent, 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.”
Participants were randomly assigned to receive either asundexian, 50 mg once daily, or a placebo, in addition to standard antiplatelet therapy such as aspirin.
The average age of participants was 68, 25 per cent were over 75, and 33 per cent were women.
Most participants, 95 per cent, had experienced a non-cardioembolic stroke, while the remainder had a high-risk transient ischaemic attack.
Non-cardioembolic strokes account for the majority of ischaemic strokes, and the trial enrolled a widely representative sample of these patients.
Patients were followed regularly at one month and three months, and then at three-month intervals to track outcomes.
Researchers found that 6.2 per cent of patients taking asundexian experienced another ischaemic stroke, compared with 8.4 per cent of those taking placebo, a 26 per cent reduction.
Major cardiovascular events occurred in 9.2 per cent of the asundexian group, compared with 11.1 per cent on placebo, a 17 per cent reduction.
Disabling or fatal strokes occurred in 2.1 per cent of patients taking asundexian versus 3 per cent in the placebo group, a 31 per cent reduction. No increase in bleeding was observed.
Ashkan Shoamanesh, co-principal investigator of the study and PHRI senior scientist, said: “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.
“That’s something physicians, patients, and families have been waiting for.”
Asundexian works differently from existing anti-clotting drugs by blocking Factor XIa, a protein involved in harmful clot formation but which plays only a small role in stopping bleeding.
By blocking Factor XIa, asundexian aimed to prevent dangerous clots while preserving the body’s natural bleeding control.
OCEANIC-STROKE is described as the first completed phase III trial of a Factor XIa inhibitor for secondary stroke prevention.
Previous studies evaluating long-term secondary stroke prevention have failed because of lack of efficacy, increased bleeding, or both.
Sharma added: “This trial marks a major step toward safer and more effective long-term treatment for stroke prevention.
“It was completed with remarkable scale and efficiency right here in Canada through our global research network.”
Asundexian is still under regulatory review and is not yet approved for clinical use.
