Physicians' Academy for Cardiovascular Education

Factor Xa inhibitor shows lack of efficacy with increased bleeding in patients with embolic stroke of undetermined source

Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source

Literature - Hart RG, Sharma M, Mundl H, et al. - N Engl J Med 2018; published online ahead of print

Introduction and methods

Embolic strokes of undetermined source are non-lacunar, and not caused by a proximal arterial stenosis, neither by a recognized cardioembolic source, such as atrial fibrillation (AF) of left ventricular thrombus, and they account for about 20% of all ischemic strokes [1-3]. Rivaroxaban, a direct factor Xa inhibitor, is indicated for the prevention of stroke in patients with AF, however, it is not known whether it is effective for the prevention of recurrent stroke in patients with embolic stroke of undetermined source.

In the NAVIGATE ESUS (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source) study [4,5], the efficacy and safety of rivaroxaban for the prevention of recurrent stroke in patients with recent embolic stroke of undetermined source was evaluated.

In the randomized, phase 3 NAVIGATE ESUS trial, eligible patients were assigned to receive either rivaroxaban 15 mg plus placebo or aspirin 100 mg plus placebo in a 1:1 ratio. Patients were eligible for the study if they:

A classifying stroke had to fulfill the following criteria:

The National Institutes of Health Stroke Scale (NIHSS) score was used to assess the stroke severity at baseline. The primary efficacy outcome was the time-to-event of first ischemic, hemorrhagic, or undefined recurrent stroke or systemic embolism. The primary safety outcome was major bleeding according to the International Society of Thrombosis and Hemostasis (ISTH) criteria.

Main results


Rivaroxaban therapy did not result in a reduction of stroke recurrence and did result in a higher rate of bleeding in patients with embolic stroke of undetermined source compared to aspirin. Ongoing trials are testing other anticoagulants compared to aspirin in similar groups of patients.


Show references

Find this article online at N Engl J Med

Share this page with your colleagues and friends: