Stroke Risk Reduced With Rivaroxaban in Embolic Stroke of Undetermined Source

Rivaroxaban was associated with a reduced recurrent stroke risk in patients with embolic stroke of undetermined source.

Rivaroxaban is associated with a reduced risk for recurrent stroke in patients with an embolic stroke of undetermined source (ESUS) and moderate to severe left atrial enlargement, according to the results of a secondary analysis published in JAMA Neurology.1

ESUS make up 20% of all ischemic strokes and have a recurrence rate of 3% to 6% per year.2 In addition, studies have demonstrated that atrial fibrillation (AF) can be detected in patients with ESUS and because anticoagulation is highly effective in preventing AF-related stroke, it might also be used to reduce stroke recurrence after ESUS.2-6 However, 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) clinical trial demonstrated no reduction in stroke with rivaroxaban 15 mg/day compared with aspirin in patients who have had an ESUS.7

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Therefore, researchers performed a secondary analysis to determine whether rivaroxaban is associated with a reduction of recurrent stroke in 7112 patients with ESUS who are at an increased risk for AF.1

These patients were stratified by clinical predictors of AF, left atrial diameter, and frequency of premature atrial contractions.

They found that there was a significant reduction in recurrent stroke only in patients with a left atrial diameter >4.6 cm (9% of the overall population) that had been treated with rivaroxaban compared with patients who received aspirin (P =.02).

The researchers concluded that, “Rivaroxaban was associated with a reduced risk of recurrent stroke among patients with ESUS and moderate or severe left atrial enlargement; however, this needs to be independently confirmed before influencing clinical practice.”1


1. Healey JS, Gladstone DJ, Swaminathan B, et al. Recurrent stroke with rivaroxaban compared with aspirin according to predictors of atrial fibrillation: Secondary analysis of  the NAVIGATE ESUS randomized clinical trial [published online April 8, 2019]. JAMA Neurol. doi:10.1001/jamaneurol.2019.0617

2. Hart RG, Diener HC, Coutts SB, et al; Cryptogenic Stroke/ESUS International Working Group. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol. 2014;13(4):429-438.

3. Sanna T, Diener HC, Passman RS, et al; CRYSTAL AF Investigators. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med. 2014;370(26):2478-2486.

4. Gladstone DJ, Spring M, Dorian P, et al; EMBRACE Investigators and Coordinators. Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med. 2014;370(26):2467-2477.

5. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146(12):857-867.

6. Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955-962.

7. Kasner SE, Lavados P, Sharma M, et al; NAVIGATE ESUS Steering Committee and Investigators. Characterization of patients with embolic strokes of undetermined source in the NAVIGATE ESUS randomized trial. J Stroke Cerebrovasc Dis. 2018;27(6):1673-1682.