TOPLINE:

Among patients with atrial fibrillation (AF) who experienced an ischaemic stroke despite oral anticoagulation, nearly 1 in 4 had competing aetiologies beyond cardioembolism and faced a higher risk for recurrent stroke, all-cause mortality, functional disability, and bleeding.

METHODOLOGY:

• Researchers conducted a retrospective observational study to assess the effect of competing stroke aetiologies on 90‑day outcomes in patients with AF who experienced a breakthrough ischaemic stroke while on oral anticoagulants.
• The study included 1649 patients with AF (mean age, 78 years; 47.8% men) who experienced an ischaemic stroke, either first ever or recurrent, while on continuous oral anticoagulants across 35 stroke centres in Europe and North Africa between 2020 and 2025.
• Patients were categorised as those with competing stroke aetiologies, defined as the presence of at least one plausible non-cardioembolic mechanism potentially contributing to the index stroke (n = 806), and those without (n = 843).
• The primary outcome was recurrent ischaemic stroke within 90 days; secondary outcomes included functional disability measured using the modified Rankin scale (mRS), myocardial infarction, all-cause mortality, vascular death, and safety outcomes.

TAKEAWAY:

• Overall, 24.3% of patients had competing stroke aetiologies, most commonly large artery atherosclerosis.
• The 90-day risk for recurrent ischaemic stroke was higher among patients with competing aetiologies than among those without (adjusted hazard ratio, 2.62; P < .001), with the risk being higher in those with large artery atherosclerosis and other determined causes.
• Patients with competing aetiologies had 30% higher odds of worse functional disability on the mRS and a 58% higher risk for all-cause mortality than those without competing aetiologies (P < .05 for both); the risk for myocardial infarction and vascular death did not differ significantly between the two groups.
• The 90-day risk for moderate-to-severe bleeding was 82% higher in patients with competing aetiologies than in those without (P = .026); however, the risk for intracranial haemorrhage was comparable between the two groups.

IN PRACTICE:

"[The study] findings highlight the clinical complexity of breakthrough strokes on OAC [oral anticoagulation], where both index and recurrent events may result from the coexistence of AF-related cardioembolism and other mechanisms," the authors wrote.

"Optimizing secondary prevention should extend beyond anticoagulation strategies to include rigorous management of cardiovascular comorbidities, such as statin use, blood pressure control, and other risk factor modifications," they added.

SOURCE:

This study was led by Matteo Foschi, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy. It was published online on April 13, 2026, in Neurology.

LIMITATIONS:

Because the study was retrospective and observational, it may have introduced residual confounding. Those patients treated outside stroke units may have been missed, limiting causal inference. Additionally, data on previous stroke/transient ischaemic attack occurred during anticoagulation treatment and its cause were not available.

DISCLOSURES:

The authors disclosed no targeted funding for this study. Several authors declared receiving consulting fees, speaker fees, and/or advisory board fees from various pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.