Apixaban did not prevent recurrent stroke vs. aspirin in atrial cardiopathy without AF
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Key takeaways:
- Apixaban did not reduce recurrent stroke risk in patients with atrial cardiopathy without AF.
- The ARCADIA trial was stopped early for futility.
Anticoagulation with apixaban after cryptogenic stroke with evidence of atrial cardiopathy and no atrial fibrillation did not prevent recurrent stroke compared with aspirin, researchers reported.
The results of the multicenter, double-blind, phase 3, randomized ARCADIA trial were presented at the International Stroke Conference and simultaneously published in JAMA.
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“Atrial cardiopathy is defined as any complex of structural, architectural, contractile or electrophysiologic changes affecting the atria with the potential to produce clinically relevant manifestations. Atrial cardiopathy is strongly associated with incident atrial fibrillation and plays a role in thromboembolism related to atrial fibrillation,” Hooman Kamel, MD, neurologist at Weill Cornell Medicine, and colleagues wrote in the simultaneous publication. “The Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial was designed to test the hypothesis that anticoagulation is superior to antiplatelet therapy for preventing recurrent stroke in patients with a recent cryptogenic stroke and evidence of atrial cardiopathy.”
The ARCADIA trial was conducted jointly with the NIH StrokeNet National Coordinating Center at the University of Cincinnati and the StrokeNet National Data Management Center at the Medical University of South Carolina, as well as a Canadian coordinating center at the Population Health Research Institute.
Overall, 1,015 participants with cryptogenic stroke and evidence of atrial cardiopathy without AF were recruited at 185 sites in StrokeNet and the Canadian Stroke Consortium (mean age, 68 years; 54% women).
Participants were randomly assigned to apixaban (Eliquis, Bristol Myers Squibb/Pfizer) 5 mg once daily or 2.5 mg twice daily or to aspirin 81 mg once daily.
The primary efficacy outcome was recurrent stroke. The primary safety outcome was symptomatic intracranial hemorrhage or other major hemorrhage.
Atrial cardiopathy was defined as P-wave terminal force greater than 5,000 V × ms in ECG lead V1, serum N-terminal pro-B-type natriuretic peptide greater than 250 pg/mL or left atrial diameter index of 3 cm/m2 or more on echocardiogram.
Results of the ARCADIA trial
With a mean follow-up of 1.8 years, the ARCADIA trial was stopped for futility after a planned interim analysis.
Overall, 87.5% of participants completed the full duration of follow-up.
The primary efficacy outcomes occurred at the same annualized rate in both treatment arms (4.4% for apixaban vs. for aspirin; HR = 1; 95% CI, 0.64-1.55), according to the study.
Symptomatic intracranial hemorrhage did not occur in any patients assigned to apixaban and occurred in seven taking aspirin, with an annualized rate of 1.1%.
Moreover, other major hemorrhages occurred at an annualized rate of 0.7% in the apixaban arm compared with 0.8% in the aspirin arm (HR = 1.02; 95% CI, 0.29-3.52), according to the study.
“In patients with a recent cryptogenic stroke and evidence of atrial cardiopathy based on three readily available biomarkers, oral anticoagulant therapy with apixaban did not significantly reduce the risk of recurrent stroke compared with aspirin. Apixaban did not appear to significantly increase the risk of symptomatic intracranial hemorrhage, other major bleeding or death compared with aspirin,” the researchers wrote. “The lack of benefit of anticoagulation over aspirin in trial participants despite selection for underlying cardiac abnormalities suggests that a substantial proportion of cryptogenic strokes may arise from nonstenosing atherosclerosis.”
‘Valuable lessons’ from the ARCADIA trial
In a related editorial, Gregory M. Marcus, MD, MAS, associate chief of cardiology for research, and Bruce Ovbiagele, MD, MSc, MAS, MBA, MLS, professor of neurology at University of California, San Francisco, discussed the apparent lower rate of symptomatic intracranial hemorrhage in the apixaban arm compared with aspirin the implications for treatment of cryptogenic stroke.
“The differences in rates of intracranial hemorrhage are remarkable, and at the very least, these data should prove reassuring for patients and clinician prescribers considering apixaban when clinically indicated,” the editorial authors wrote.
“In this first major randomized trial to tackle stroke prevention in left atrial cardiopathy absent evidence of AF, apixaban failed to exhibit superior efficacy compared with low-dose aspirin,” they wrote. “On a more positive note, this well-conducted study provides several valuable lessons that will help move the field forward. For now, patients with embolic stroke of undetermined source should be treated with antiplatelet therapy and not anticoagulated.”
References:
- Kamel H, et al. JAMA. 2024;doi:10.1001/jama.2023.27188.
- Marcus GM, et al. JAMA. 2024;doi:10.1001/jama.2023.23916.
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Tirschwell DL, et al. Abstract LBP40. Presented at: International Stroke Conference; Feb. 7-9, 2024; Phoenix.
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