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Hooman Kamel, MD
Credit: LinkedIn
Results from the ARCADIA randomized clinical trial demonstrated that apixaban did not significantly reduce the risk of recurrent stroke compared with aspirin among patients with cryptogenic stroke and evidence of atrial heart disease without atrial fibrillation (AF).1
More than 1,000 participants in the multicenter, double-blind phase 3 clinical trial were randomized to receive 5 mg or 2 mg of apixaban twice daily or aspirin (81 mg) once daily. A team of Weill Cornell Medicine researchers found that the annualized rate of recurrent strokes did not differ significantly between patients treated with apixaban and aspirin, at 4.4% in both cohorts.
“In patients with a recent cryptogenic stroke and evidence of atrial heart disease based on 3 readily available biomarkers, oral anticoagulant therapy with apixaban did not significantly reduce the risk of recurrent stroke compared with aspirin,” wrote the research team, led by Hooman Kamel, MD. .
Kamel and colleagues set out to compare anticoagulation versus antiplatelet therapy for secondary stroke prevention in a population with cryptogenic stroke and evidence of atrial heart disease. The ARCADIA trial involved participants with cryptogenic stroke and evidence of atrial heart disease; this was measured as terminal P wave force ≥5000 µV x ms in lead LV of the electrocardiogram, serum N-terminal pro-B-type natriuretic peptide ≥250 pg/mL, or left atrial diameter index ≥3 cm/min. m2 on the echocardiogram.
The included population had no evidence of atrial fibrillation (AF) at the time of randomization. Enrollment and follow-up occurred from early to late February 2023 at 185 National Institutes of Health StrokeNet and Canadian Stroke Consortium sites. A total of 507 people received 5 mg or 2.5 mg of apixaban twice daily and 508 received aspirin (81 mg) once daily during the study period.
In the time-to-event analysis of the ARCADIA trial, the primary efficacy endpoint was recurrent stroke of any type. Safety outcomes in the analysis were symptomatic intracranial hemorrhage and other major hemorrhage. The entire population, including those diagnosed with AF after trial randomization, was evaluated according to their randomization group.
A total of 1,015 participants out of the target 1,100 were enrolled in the study, with a mean follow-up period of 1.8 years. As the hazard ratio (HR) for apixaban versus aspirin was within prespecified interim limits of futility, the trial was stopped after the planned interim analysis. Participants had a mean age of 68.0 years, 54.3% were women, and 87.5% completed the full follow-up period.
Upon analysis, the primary outcome of recurrent stroke was identified in 40 patients in the apixaban group (annualized rate, 4.4%) and 40 patients in the aspirin group (annualized rate, 4.4%) (HR, 1.00 [95% CI, 0.64 – 1.55]). A post hoc analysis performed in 149 patients with documented AF after randomization also found no significant difference in the rate of recurrent stroke between apixaban (annualized rate, 1.8%) and aspirin (annualized rate, 2.2%) (HR , 0.84 [95% CI, 0.19 – 3.74]).
Secondary efficacy outcomes of recurrent stroke or death were observed in 67 patients in the apixaban group (annualized rate, 7.3%) and 62 patients in the aspirin group (annualized rate, 6.8%) (HR, 1 .08 [95% CI, 0.76 – 1.52]). Safety results showed that symptomatic intracranial hemorrhage occurred in zero patients receiving apixaban and in 7 patients receiving aspirin (annualized rate, 1.1%). Other major bleeding was identified in 5 patients receiving apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (HR, 1.02 [95% CI, 0.29 – 3.52]).
An accompanying editorial by Bruce Ovbiagele, MD, MSc, department of neurology, University of California, San Francisco, suggested that the ARCADIA trial does not necessarily conclude treatability based on the presence of atrial heart disease, independent of AF.2
Although outcome analyzes focusing on the inclusion criteria did not achieve statistically significant results, Ovbiagele noted that point estimates favored protection with apixaban among those selected using the P-wave terminal force criterion and damage among those with a high level. of NT-proBNP.
“These data may suggest that future efforts to identify optimal therapeutic strategies for patients with atrial heart disease should focus on markers that most directly reflect left atrial pathology,” Ovbiagele wrote.
References
- Kamel H, Longstreth WT, Tirschwell DL, et al. Apixaban for preventing recurrence after cryptogenic stroke in patients with atrial heart disease: ARCADIA randomized clinical trial. JAMA. Published online February 7, 2024. doi:10.1001/jama.2023.27188
- Marcus GM, Ovbiagele B. Anticoagulation for atrial heart disease in cryptogenic stroke. JAMA. Published online February 7, 2024. doi:10.1001/jama.2023.23916