Rivaroxaban for secondary stroke prevention in patients with embolic strokes of undetermined source: Design of the NAVIGATE ESUS randomized trial

Abstract

Background: Embolic strokes of undetermined source comprise up to 20% of ischemic strokes. The stroke recurrence rate is substantial with aspirin, widely used for secondary prevention. The New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus ASA to prevenT Embolism in Embolic Stroke of Undetermined Source international trial will compare the efficacy and safety of rivaroxaban, an oral factor Xa inhibitor, versus aspirin for secondary prevention in patients with recent embolic strokes of undetermined source. Main hypothesis: In patients with recent embolic strokes of undetermined source, rivaroxaban 15 mg once daily will reduce the risk of recurrent stroke (both ischemic and hemorrhagic) and systemic embolism (primary efficacy outcome) compared with aspirin 100 mg once daily. Design: Double-blind, randomized trial in patients with embolic strokes of undetermined source, defined as nonlacunar cryptogenic ischemic stroke, enrolled between seven days and six months from the qualifying stroke. The planned sample size of 7000 participants will be recruited from approximately 480 sites in 31 countries between 2014 and 2017 and followed for a mean of about two years until at least 450 primary efficacy outcome events have occurred.

Microbleeds in ischemic vs hemorrhagic strokes on novel oral anticoagulants

“…We assessed CMBs and gov, NCT02513316; and HERO, NCT02238470) as well as imaging substudies of randomized clinical trials in patients with embolic stroke of undetermined source are expected to further clarify the benefit-risk ratio of oral anticoagulation in individual patients with CSVD. [28][29][30][31]…”

Rivaroxaban versus aspirin for secondary prevention of ischaemic stroke in patients with cancer: a subgroup analysis of the NAVIGATE ESUS randomized trial

“…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) trial is an international randomized phase III trial. The design of the trial and the baseline characteristics of the 7213 enrolled individuals have recently been reported . Rivaroxaban was not superior to aspirin in preventing recurrent ischaemic strokes in the NAVIGATE ESUS trial .…”

Clinical and Neuroimaging Characteristics in Embolic Stroke of Undetermined versus Cardioembolic Origin: A Population‐Based Study

“…We identified 21 ESUS (3.7% of the IS cohort) and 211 CE patients (37.1% of the IS cohort). Baseline characteristics and outcomes between ESUS patients and CE patients are presented in Table 1 [5][6][7][8][9][10][11][12][13][14][15][16][17]; P < .001), had higher prevalence of smoking (57.1 vs 15.6%, P < .001), had less often positive family history for cardiovascular disease (38.1 vs 73%, P < .001). Male sex was less common in ESUS (28.6 vs 59.2%; P = .007).…”

“…5,6 Since cardioembolism (due to AF or other causes) was speculated to be the primary underlying mechanism in ESUS, the efficacy of NOACs over low-dose aspirin for the secondary prevention of ESUS was recently tested in two large randomizedcontrolled clinical trials. 7,8 Both studies failed to show superiority of NOACs (dabigatran and rivaroxaban) over aspirin and challenged the hypothesis that occult AF may represent the main etiopathogenic mechanism of ESUS. Moreover, in the rivaroxaban treatment arm there was a statistically significant excess of intracranial hemorrhages (0.7 vs 0.1%, hazard ratio [HR]: 6.5, CI: 1.47-28.8).…”