Asundexian reduces risk of recurrent stroke without increasing the risk of bleeding

Asundexian, an investigational anti clotting medication, appears to lower the risk of stroke without increasing bleeding in patients who have had a recent stroke or transient ischemic attack (TIA) caused by a clot forming outside of the heart (non-cardioembolic stroke).

Findings from the OCEANIC STROKE trial were published in The New England Journal of Medicine (NEJM) on April 15, 2026.

“This is something researchers have been working toward for decades,” said Mike Sharma, MD, 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 in Hamilton, Ontario, Canada. “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.”

As background to the phase 3 trial, the authors noted that patients with non-cardioembolic ischemic stroke or transient ischemic attack (TIA) are at elevated for recurrent stroke. “Low factor XI levels are associated with a reduced risk of ischemic stroke. Asundexian inhibits activated factor XI.”

The study was designed to determine whether the addition of asundexian to antiplatelet therapy would be superior to antiplatelet therapy monotherapy for the secondary prevention of ischemic stroke.

The investigators randomized 12,327 adult subjects within 72 hours of a non cardioembolic stroke or a temporary blockage of blood flow to the brain (TIA). Each subject had at least one of the following —  a nonlacunar infarct on imaging, a history of atherosclerosis or evidence of atherosclerotic plaque at any location on cerebrovascular imaging.

The average age of the subjects was 68 years; 25 per cent were over the age of 75, and 33 per cent were women.

The researchers noted that, “Currently, preventing another stroke in these situations relies mainly on antiplatelet medications, a type of anti-clotting medication that reduces risk only modestly and increases bleeding when combined or used for long term.”

The subjects received asundexian (50 mg once daily) or placebo, in addition to  dual or single antiplatelet therapy.

The primary efficacy outcome was ischemic stroke. The primary safety outcome was major bleeding.

Subjects 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 ischemic stroke, compared with 8.4 per cent of those taking placebo, a 26 per cent reduction in this primary outcome. They also found that 9.2 per cent of the subjects experienced a major cardiovascular event (stroke, heart attack or cardiovascular death), compared with 11.1 per cent on placebo (17 per cent reduction).

Disabling or fatal strokes occurred in 2.1 per cent of patients taking asundexian versus three per cent in the placebo group (31 per cent reduction).

There was no increase in bleeding among subjects treated with asundexian.

The authors concluded, “Among patients with non-cardioembolic ischemic stroke or high-risk TIA treated with antiplatelet therapy, asundexian at a daily dose of 50 mg resulted in lower risks of ischemic stroke and major cardiovascular events than placebo, without a higher risk of major 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,” added Ashkan Shoamanesh, co principal investigator of the study and PHRI senior scientist. “That’s something physicians, patients and families have been waiting for.”