TOPLINE

Patients with atrial fibrillation (AF) who experienced breakthrough ischemic stroke despite anticoagulation often had identifiable causes — mainly interacting drugs or non-cardioembolic mechanisms — and faced increased short-term risks for recurrence and heart attack.

METHODOLOGY

• Researchers analyzed data from the retrospective arm of the ASPERA study to identify causes of ischemic stroke that occurred despite ongoing oral anticoagulation in patients with AF and to assess their impact.
• They included 1649 patients (median age, 80.4 years; 52.2% women) treated at 35 stroke centers between February 2020 and February 2025. Most patients (77.3%) were on direct oral anticoagulants.
• Patients took anticoagulant continuously in the prior 7 days before the ischemic stroke, with a last direct oral anticoagulant dose within 48 hours. Vitamin K antagonist users had an international normalized ratio ≥ 1.5.
• Potential causes of oral anticoagulation failure were categorized as drugs with known interactions, competing non-cardioembolic stroke etiologies, and active cancer.
• The primary outcome was the 90-day occurrence of new ischemic stroke. Secondary outcomes included 90-day functional outcome, myocardial infarction, all-cause death, and vascular death.

TAKEAWAY

• Overall, 43.9% of patients had at least one potential cause of anticoagulation failure; 28.4% were taking drugs with known interactions, 24.3% had competing non-cardioembolic etiologies, and 4.4% had active cancer.
• Patients with at least one potential cause had a higher risk for 90-day new ischemic stroke compared with those without a potential cause (adjusted hazard ratio, 2.04; P = .011).
• Concomitant interacting drugs were associated with a 3.26-fold increased 90-day risk for myocardial infarction in a weighted analysis (P = .012) and were not associated with a higher risk for recurrent ischemic stroke.
• All-cause and vascular death rates at 90 days did not differ significantly between patients with and without a potential cause, or between those taking and not taking interacting drugs.

IN PRACTICE

"Our results highlight the need for personalized secondary prevention approaches to patients with breakthrough stroke including statins, antiplatelet treatments, and/or other drugs, as breakthrough stroke might depend in many cases on alternative stroke mechanisms rather than on insufficient anticoagulation," the authors wrote.

SOURCE

The study was led by Federico De Santis, University of L'Aquila in L'Aquila, Italy. It was published online on August 17 in Journal of Neurology.

LIMITATIONS

The study was retrospective and carried risks for selection and information bias. Compliance to direct oral anticoagulants was retrieved from clinical history only. Some patients may have lacked diagnostic tests such as echocardiography, which may have affected how causes of stroke were determined.

DISCLOSURES

The study did not receive any funding. Several authors reported receiving consulting fees, speaker fees, advisory board fees, or other compensation from various pharmaceutical, biotechnology, and medical device companies. Detailed author disclosures are reported in the original article.

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