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Antithrombotic therapy represents the mainstay in primary and secondary prevention, both in cardioembolic and non-cardioembolic stroke. Particularly, direct oral anticoagulants play a crucial role in atrial fibrillation, the most common cause of cardioembolic stroke, whereas single or dual antiplatelet therapy is preferred in non-cardioembolic stroke. However, the limitations related to the residual risk of cardioembolic or cerebrovascular events, and the risk of major bleeding, still represent unmet medical needs. To overcome them, new drugs inhibiting Factor XI (FXI) and Factor XII have been proposed, with a selective inhibition of contact pathway of coagulation, delineating a new anticoagulant approach. This review provides a summary of the currently available evidence and future perspectives on FXI inhibitors, that can represent an additional therapeutic option in the primary and secondary prevention of cardioembolic and non-cardioembolic ischemic stroke, also in challenging therapeutic contexts.<\/jats:p>\n                <jats:p><jats:bold>Graphical Abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s11739-024-03611-w","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T13:02:16Z","timestamp":1715691736000},"page":"1807-1819","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Factor XI Inhibitors: perspectives in primary and secondary prevention of ischemic stroke"],"prefix":"10.1007","volume":"19","author":[{"given":"Domenico","family":"Prisco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Canfora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Mazzetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Mattioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Bettiol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,14]]},"reference":[{"key":"3611_CR1","first-page":"795","volume":"20","author":"GBD","year":"2019","unstructured":"GBD (2019) Stroke Collaborators (2021) Global, regional, and national burden of stroke and its risk factors, 1990\u20132019: a systematic analysis for the Global Burden of Disease Study 2019. 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