Can an antithrombotic meaningfully reduce the risk of recurrent ischemic stroke without increasing major bleeding? Drs. Mike Sharma, Ashkan Shoamanesh, and Brian Mac Grory explore the science behind factor XIa inhibition and its potential to decouple thrombosis from hemostasis. The panel reviews pivotal OCEANIC-STROKE results presented at ISC 2026, highlighting a 26% relative risk reduction in ischemic stroke without an observed increase in ISTH major bleeding. They examine outcomes across stroke subtypes and place these results in context with other agents in development, such as milvexian and abelacimab. This conversation considers whether factor XI inhibition may alter long-standing assumptions about the tradeoff between efficacy and safety in secondary stroke prevention.