1. In this post-hoc analysis of data from the NAVIGATE-ESUS trial, which evaluated strategies to prevent recurrent stroke in patient of embolic stroke of undetermined source, use of rivaroxaban was linked with a lower risk of recurrent stroke compared to aspirin in patients with moderate to severe left atrial enlargement.
2. Use of rivaroxaban in patients with high burden of premature atrial contractions or clinical risk of atrial fibrillation was not shown to reduce the risk of recurrent stroke compared to aspirin.
Evidence Rating Level: 2 (Good)
Study Rundown: The management of embolic strokes of undetermined source (ESUS) remains an area of active investigation. Many patients are thought to have underlying atrial fibrillation (AF) that has gone undetected. Starting some of these patients on anticoagulation may provide benefit over antiplatelet therapy. The New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial versus ASA To Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial compared rivaroxaban 15mg daily to aspirin 100 daily for patients with ESUS. In the initial study there was no significant benefit of rivaroxaban and a higher rate of bleeding. The current study sought to evaluate whether subgroups of patients at increased risk of AF may benefit from anticoagulation with rivaroxaban. The study found that clinical scoring systems for AF and burden of premature atrial contractions (PACs) predicted risk of subsequent AF diagnosis but did not impact statistical benefit from rivaroxaban therapy. However, in patients with left atrial enlargement, use of rivaroxaban was associated with a considerably lower risk of recurrent stroke compared to use of aspirin.
The main strength of this study was the large population of participants for whom complete data including clinical history, rhythm monitoring, and echocardiographic investigations were available. The main limitations of the study were the short period of follow-up and post-hoc design. Despite its limitations, the analysis provides evidence of a substantial benefit of rivaroxaban therapy in patient with ESUS and atrial enlargement and provides direction for future research.
In-Depth [randomized controlled trial]: This study was a post-hoc analysis of data from the NAVIGATE ESUS trial, a randomized control trial of patients with ESUS. Participants were included if they had an ischemic stroke confirmed on CT or MRI, had a non-lacunar site of infarct, had <50% stenosis of vessels proximal to the infarct, and no evidence of cardioembolic source. Patients found to have AF were excluded from the analysis. Participants were randomized to rivaroxaban 15 mg orally daily or aspirin 100 mg orally daily. Risk of AF was evaluated using left atrial diameter, burden of PACs, and the HAVOC clinical prediction score. The primary outcome was recurrent ischemic stroke based on imaging or autopsy findings.
The 7112 patients in this study were followed for a median of 11 months, with 239 having subsequent diagnosis of AF during the study period. The HAVOC prediction score and burden of PACs did not influence the association of rivaroxaban use and recurrent stroke (P for interaction = .67 and .96, respectively). In patients with left atrial diameter greater than 4.6 cm the use of rivaroxaban was linked to a lower risk of recurrent stroke compared to aspirin (hazard ratio, 0.26; 95%CI, 0.07-0.94; P for interaction = .02).
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