About Index

NAVIGATE ESUS

"Rivaroxaban versus Aspirin in Secondary Prevention of Stroke and Prevention of Systemic Embolism in Patients with Recent Embolic Stroke of Undetermined Source (NAVIGATE ESUS)". The New England Journal of Medicine. 2018.

Links to original sources: Wiki Journal Post Full Journal Article

Clinical Question


Does rivaroxaban, an oral factor Xa inhibitor, reduce the risk of recurrent stroke compared to aspirin in patients with recent embolic strokes of undetermined source?

Bottom Line


Rivaroxaban did not reduce the risk of recurrent stroke compared to aspirin in patients with recent embolic strokes of undetermined source and was associated with a higher risk of bleeding.

Major Points


Embolic strokes of undetermined source account for approximately 20% of ischemic strokes. Anticoagulants may be more effective than antiplatelet therapy for preventing recurrent strokes in these patients. The NAVIGATE ESUS trial compared the efficacy and safety of rivaroxaban with aspirin for the prevention of recurrent stroke or systemic embolism in patients with recent strokes of undetermined source.

Guidelines


Guidelines for secondary prevention of stroke in the context of embolic strokes of undetermined source would need to reflect the results of this trial.

Design


Randomized, double-blind, event-driven, phase 3 trial at 459 centers in 31 countries.

Population


Patients with recent ischemic stroke of undetermined source without arterial stenosis, cardioembolic source, or other determined causes. 7213 participants were enrolled.

Inclusion Criteria: - Ischemic stroke without a clear source - Absence of proximal arterial stenosis, known cardioembolic source, or lacune - Stroke occurrence between 7 days and 6 months prior to screening

Exclusion Criteria: - History of atrial fibrillation - Severe stroke (modified Rankin score ≥4) - Indication for anticoagulation or antiplatelet therapy beyond study parameters

Interventions


- Rivaroxaban (15 mg daily) - Aspirin (100 mg daily)

Outcomes


Primary Efficacy Outcomes: - Recurrence of ischemic or hemorrhagic stroke or systemic embolism - Rivaroxaban group: 172 patients (5.1% annualized rate) - Aspirin group: 160 patients (4.8% annualized rate)

Outcomes


- Major bleeding events - Rivaroxaban group: 62 patients (1.8% annualized rate) - Aspirin group: 23 patients (0.7% annualized rate)

Criticisms


- The trial was stopped early due to the lack of benefit and increased bleeding risk with rivaroxaban. - A majority of the included patients had minor residual deficits at trial entry (median NIHSS score of 1).

Funding


Bayer and Janssen Research and Development.

Further Reading


- Full trial manuscript as published in The New England Journal of Medicine - Other relevant trials on secondary stroke prevention and the use of anticoagulation in embolic strokes of undetermined source