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Apixaban Fails to Prevent Recurrence after Cryptogenic Stroke With Atrial Cardiopathy

May 24, 2024

June 2024

Lara C. Pullen, PhD

Lara C. Pullen, PhD, is a freelance medical writer in Chicago, Illinois.

Prospective observational studies have found that three biomarkers of atrial cardiopathy are associated with the risk of ischemic stroke. These results have led investigators to seek a way to identify proactive therapies that capitalize on these findings. Now, research has found that, in patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban does not significantly reduce recurrent stroke risk when compared to aspirin. Hooman Kamel, MD, vice chair for research and chief of neurocritical care in the Department of Neurology at Weill Cornell Medicine in New York City, and colleagues published the findings from the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) randomized clinical trial in JAMA.

The objective of the ARCADIA trial was to compare anticoagulation versus antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy. The investigators used three readily available biomarkers to screen 3,745 patients with cryptogenic stroke to determine if they had atrial cardiopathy. Patients were included in the study if they met at least one of the atrial cardiopathy biomarker criteria as measured by: P-wave terminal force in echocardiogram lead V1, serum N-terminal pro-B-natriuretic peptide, and left atrial diameter. Few patients with cryptogenic stroke had any degree of atrial enlargement as their only inclusion criteria. Those patients with mild to moderate left atrial enlargement were included based on meeting other criteria. Another limitation of the study, the authors noted, was that it was conducted during the COVID-19 pandemic and participants withdrew from the trial at a higher-than-expected rate.

The investigators randomized patients to receive apixaban at 5 mg or 2.5 mg twice daily (n=507) or aspirin at 81 mg once daily (n=508) and followed them for an average of 1.8 years. The average age of the participants was 68.0 years, 54.3% were female, 21.1% were Black or African American, and 8.1% were Hispanic or Latino. The majority (87.5%) completed the full duration of follow-up. Although patients had no signs of atrial fibrillation at the time of randomization, atrial fibrillation was diagnosed in 149 patients (14.7%) at a median of 30 weeks after randomization. The investigators stopped the trial for futility after a planned interim analysis that occurred after 75 primary outcome events of recurrent stroke. They saw no indications of safety concerns.

Recurrent stroke occurred in 40 patients in the apixaban group (annualized rate = 4.4%) and 40 patients in the aspirin group (annualized rate = 4.4%) for a hazard ratio of 1.00 (95% CI 0.64-1.55). Symptomatic intracranial hemorrhage occurred in no patients in the apixaban group and seven patients in the aspirin group (annualized rate = 1.1%). Other major hemorrhages occurred in five patients taking apixaban (annualized rate = 0.7%) and five patients taking aspirin (annualized rate = 0.8%) for a hazard ratio of 1.02 (95% CI 0.29-3.52).

“We know anticoagulation works in patients who have stroke and atrial fibrillation,” said Mitchell S.V. Elkind, MD, professor of neurology and epidemiology at Columbia University in New York City and coauthor of the paper. “Aspirin is what we would consider the standard of care.”

In their discussion, the authors hypothesized that the disappointing results could be because the previously demonstrated associations between atrial cardiopathy and stroke may have been confounded by atherosclerosis. Although he described the study results as disappointing, Dr. Elkind pointed out another clinically interesting finding from their study, saying, “There was no increased risk of bleeding in people who were on apixaban as compared to aspirin.”

Any conflicts of interest declared by the authors can be found in the original article.

Reference

Kamel H, Longstreth WT, Tirschwell DL, et al. Apixaban to prevent recurrence after cryptogenic stroke in patients with atrial cardiopathy: The ARCADIA Randomized Clinical Trial. JAMA. 2024;331(7):573-581.

 

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