Perspective:

With the usual concerns about post-hoc analyses in mind, this important analysis offers insight about the relative safety of discontinuing rivaroxaban in the setting of AF. There did not appear to be any statistically significant difference between agents after temporary interruptions or early permanent discontinuation. However, for the single endpoint of stroke, when transitioning from rivaroxaban to open-label therapy at the end of the study, there appeared to be significantly more strokes observed transitioning from rivaroxaban to warfarin, than when continuing with warfarin. (A difference was not seen when all potentially thrombotic events—including myocardial infarction and vascular death—within 30 days of study drug cessation were evaluated.) These data strongly suggest an increased risk of stroke when transitioning from rivaroxaban to warfarin in AF patients. What remains unclear at this point, however, is whether the discontinuation of rivaroxaban while transitioning to warfarin therapy induces a prothrombotic or hypercoagulable state, or merely results in a period of therapeutic under-anticoagulation. Further study is clearly needed to clarify this important point. If the problem is simply the potential for under-anticoagulation during transition, then this would suggest that the initiation of anticoagulation with warfarin in patients with AF may require bridging anticoagulation. If, on the other hand, cessation of rivaroxaban appears to induce a prothrombotic state, such drug cessation will have to be handled with care, or with a tapered reduction of therapy.