Novel anti-clotting medication cuts chance of stroke without risk of added bleeding

The Phase 3 OCEANIC-STROKE has shown that Factor XIa inhibition with asundexian reduces recurrent stroke and major cardiovascular events without increasing bleeding risk

A large international clinical trial has found that asundexian, an investigational anticoagulant, has reduced the risk of recurrent stroke in patients who recently experienced a non-cardioembolic stroke or transient ischaemic attack, without an associated increase in bleeding risk. The findings have addressed a longstanding limitation in secondary stroke prevention, where gains in efficacy have often come at the cost of further haemorrhagic complications.

The OCEANIC-STROKE trial enrolled 12,327 adults across 37 countries within 72 hours of an index event – defined as either a non-cardioembolic stroke or a transient ischaemic attack, the latter a temporary interruption of cerebral blood flow that signals heightened future risk. Current standard of care relies largely on antiplatelet therapy such as aspirin, which offers only modest protection and carries an increased bleeding risk when used in combination or over an extended period.

Participants were randomly assigned to receive either asundexian at a dose of 50 mg once daily or given a placebo, in addition to background antiplatelet therapy. The cohort had a mean age of 68 years, with one quarter aged more than 75 years and one third female. The vast majority had sustained a non-cardioembolic stroke, reflecting the predominant subtype of ischaemic stroke in routine clinical practice. Follow-up assessments took place at one month, three months and at regular three-month intervals thereafter to capture recurrent events and safety outcomes.

The trial demonstrated a consistent reduction in clinically meaningful endpoints. Recurrent ischaemic stroke occurred in 6.2 per cent of patients treated with asundexian compared with 8.4 per cent in the placebo group, corresponding to a relative risk reduction of 26 per cent. Major cardiovascular events, defined as stroke, myocardial infarction or cardiovascular death, affected 9.2 per cent of patients receiving asundexian versus 11.1 per cent of those on placebo, representing a 17 per cent reduction.

And, disabling or fatal stroke occurred in 2.1 per cent of the treatment group compared with three per cent in the control arm, a relative reduction of 31 per cent. Crucially, investigators reported no increase in major bleeding, which has historically limited the use of more intensive antithrombotic strategies.

“This is something researchers have been working toward for decades,” said Dr. Mike Sharma, principal investigator and senior scientist at the Population Health Research Institute, a joint institute of McMaster University and Hamilton Health Sciences, both of Hamilton, 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,” said Sharma.

“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 Dr. Ashkan Shoamanesh, co-principal investigator and senior scientist at the Population Health Research Institute.

“That’s something physicians, patients and families have been waiting for,” he added.

Mechanistically, asundexian targets coagulation Factor XIa, a component of the intrinsic pathway that contributes to pathological thrombus formation but plays a comparatively limited role in physiological haemostasis. By inhibiting Factor XIa, the drug has aimed to suppress thrombosis while preserve endogenous bleeding control, an approach that has gained increasing attention as a potential paradigm shift in anticoagulant design. The OCEANIC-STROKE findings have provided the strongest late-stage clinical evidence to date in support of this strategy.

OCEANIC-STROKE represents the first completed phase 3 trial of a Factor XIa inhibitor for secondary stroke prevention. Previous attempts to improve long-term outcomes in this setting have failed due to insufficient efficacy, unacceptable bleeding risk, or both. The scale and geographic diversity of the trial cohort have strengthened the generalisability of the findings across healthcare systems and patient populations.

“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,” Sharma added.

The trial was sponsored by Bayer AG.

For further reading please visit: 10.1056/NEJMoa2513880