In an open-label, noninferiority RCT of patient with established antiphospholipid syndrome and triple-positive antiphospholipid antibodies, rivaroxaban was asso- ciated with higher risk of thrombotic events.616 A similar result in favor of VKA over rivaroxaban was reported in an open-label RCT of patients with antiphospholipid syndrome. In this study, 60% had triple-positive antiphospholipid antibodies, but there was no statistical interaction suggestive of a differential effect among those with antiphospho- lipid syndrome and 1 or 2 antiphospholipid anti- Observational data also suggest a high risk of recurrent thrombosis among patients with antiphospholipid syndrome who receive DOACs.618 Until other ongoing trials such as ASTRO-APS (Apixaban for the Secondary Prevention of Thrombosis Among Patients With Antiphospholipid clarify whether the increased risk of thrombosis with DOACs is a class effect versus an individual drug effect, we do not recommend the use of DOACs in general and, specifically, rivaroxa- ban for antiphospholipid syndrome. Knowledge Gaps and Future Research Although thrombophilic states have been associated with a higher risk of stroke in epidemiological studies, it is uncertain whether specific treatment should be offered to people with stroke and some of these traits. Future research on treatment for hypercoagulable states and stroke should address the following: It is uncertain whether, in the absence of venous thrombosis, there is an indication for anticoagula- tion for secondary stroke prevention in people with thrombophilic states. It is uncertain whether, in the absence of venous thrombosis, the presence of a PFO may modify the risk of stroke recurrence and possible preventive strategies in people with thrombophilic states sus- pected to have paradoxical emboli. Given the relatively low prevalence of thrombophilic traits in populations with stroke, larger, adequately powered multicenter studies are needed to study each trait individually. 