Rivaroxabin for stroke prevention after embolic stroke of undetermined source

Hart RG. Rivaroxabin for stroke prevention after embolic stroke of undetermined source.  NEJM; 378: 2191-2201.  

Study tested  15 MG rivaroxaban v. 100 mg of aspirin with presumed embolic but undetermined source, with no arterial stenosis,lacunae or identified cardioembolic source.7213 patients were enrolled at 459 sites. Study was halted at eleven months with non superiority. Primary outcome was recurrent ischemic or hemorrhage stroke and primary safety measure was bleeding.   Recurrent stroke was 4.7 percent is both groups.  Bleeding occurred in 1.8 percent of rivaroxaban group, 0.7 percent of aspirin group ( p<0 .001="" a="" and="" bleeding.="" div="" effective="" had="" higher="" more="" nbsp="" not="" of="" onclusion:="" rate="" rivaroxaban="" was="">

NAVIGATE ESUS trial-- New approach rivaroxaban inhibition of factor Xa in a global trial versus aspirin to prevent embolism in embolic stroke of undetermined source.

The primary outcome of any stroke or systemic embolism slightly and non significantly favored rivaroxaban (5.1 v. 4.8 percent) There were hemorrhagic strokes in 0.4 v. 0.1 in respective groups (statistically significant but low effect size).  

Atrial fibrillation was not excluded prior to randomization.  About 12 percent of patients with cryptogenic stroke have undiagnosed atrial fibrillation.  PFO's were excluded. 

Comment-- Study is conclusive for unselected group, but what about for selected group with an educated guess of etiology? That could happen through selection of patients with certain ECHO characteristics , for example  left atrial hypertrophy or intracranial stenosis.  While one may argue that would be overkill to do the study, in the prior negative warfarin studies (WASID) patients never maintained their INR's within range..  

Power was very high to determine outcome.  Risk of stroke in first 11 months was about five percent.