Given the relatively low prevalence of thrombophilic traits in populations with stroke, larger, adequately powered multicenter studies are needed to study each trait individually. If a heightened risk of stroke is confirmed, clinical trials may be needed to evaluate whether antico- agulation may be useful to reduce the risk of stroke recurrence. There is less clarity on secondary stroke preventive mea- sures in people with antiphospholipid syndrome; conse- quently, the following knowledge gaps remain: There is an urgent need to clarify whether DOACs may be used instead of warfarin to reduce the risk of stroke in this population. There is a knowledge gap with respect to the role of dual antiplatelets in antiphospholipid syndrome, with reports suggesting a possible role to reduce the risk of stroke alone or in addition to antico- agulation. The absence of definitive data prevents us from providing a stronger recommendation at this point. Recommendation for Hyperhomocysteinemia Referenced studies that support the recommendation are summarized in online Data Supplements 46 and 47. COR LOE Recommendation Benefit B-R In patients with ischemic stroke or TIA with hyperhomocysteinemia, supplementation with folate, vitamin B6 , and vitamin B12 is not effective for preventing subsequent Synopsis Although elevated serum homocysteine has consis- tently been associated with elevated risk of stroke and other vascular events, randomized trials of folate and B vitamin supplementation have not shown ben- efit in secondary prevention of stroke. Challenges in understanding the relationship between vitamin supplementation and secondary stroke prevention stem from limitations in trial design, for example, including patients with both cardiovascular and and enrollment from countries with varying levels of folate supplementa- tion of foods. 