Faculty Collaboration Database

Apixaban to Prevent Recurrence After Cryptogenic Stroke in Patients With Atrial Cardiopathy: The ARCADIA Randomized Clinical Trial. JAMA 2024 Feb 20;331(7):573-581

Date

02/07/2024

Pubmed ID

38324415

Pubmed Central ID

PMC10851142

DOI

10.1001/jama.2023.27188

Scopus ID

2-s2.0-85184819742 (requires institutional sign-in at Scopus site)   5 Citations

Abstract

IMPORTANCE: Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation.

OBJECTIVE: To compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy.

DESIGN, SETTING, AND PARTICIPANTS: Multicenter, double-blind, phase 3 randomized clinical trial of 1015 participants with cryptogenic stroke and evidence of atrial cardiopathy, defined as P-wave terminal force greater than 5000 μV × ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250 pg/mL, or left atrial diameter index of 3 cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomization. Enrollment and follow-up occurred from February 1, 2018, through February 28, 2023, at 185 sites in the National Institutes of Health StrokeNet and the Canadian Stroke Consortium.

INTERVENTIONS: Apixaban, 5 mg or 2.5 mg, twice daily (n = 507) vs aspirin, 81 mg, once daily (n = 508).

MAIN OUTCOMES AND MEASURES: The primary efficacy outcome in a time-to-event analysis was recurrent stroke. All participants, including those diagnosed with atrial fibrillation after randomization, were analyzed according to the groups to which they were randomized. The primary safety outcomes were symptomatic intracranial hemorrhage and other major hemorrhage.

RESULTS: With 1015 of the target 1100 participants enrolled and mean follow-up of 1.8 years, the trial was stopped for futility after a planned interim analysis. The mean (SD) age of participants was 68.0 (11.0) years, 54.3% were female, and 87.5% completed the full duration of follow-up. 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%) (hazard ratio, 1.00 [95% CI, 0.64-1.55]). Symptomatic intracranial hemorrhage occurred in 0 patients taking apixaban and 7 patients taking aspirin (annualized rate, 1.1%). Other major hemorrhages occurred in 5 patients taking apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (hazard ratio, 1.02 [95% CI, 0.29-3.52]).

CONCLUSIONS AND RELEVANCE: In patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03192215.

Author List

Kamel H, Longstreth WT Jr, Tirschwell DL, Kronmal RA, Marshall RS, Broderick JP, Aragón García R, Plummer P, Sabagha N, Pauls Q, Cassarly C, Dillon CR, Di Tullio MR, Hod EA, Soliman EZ, Gladstone DJ, Healey JS, Sharma M, Chaturvedi S, Janis LS, Krishnaiah B, Nahab F, Kasner SE, Stanton RJ, Kleindorfer DO, Starr M, Winder TR, Clark WM, Miller BR, Elkind MSV, ARCADIA Investigators

Author

Marc A. Lazzaro MD Associate Professor in the Neurology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Anticoagulants
Aspirin
Atrial Fibrillation
Canada
Double-Blind Method
Female
Heart Diseases
Hemorrhage
Humans
Intracranial Hemorrhages
Male
Pyrazoles
Pyridones
Stroke