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We summarize the major advances in stroke prevention for patients with atrial fibrillation during the past 30 years and focus on novel diagnostic and treatment approaches currently under investigation in ongoing clinical trials. Non\u2013vitamin K antagonist oral anticoagulants have been proven to be safer and equally effective compared with warfarin in stroke prevention for patients with nonvalvular atrial fibrillation. Non\u2013vitamin K antagonist oral anticoagulants are being investigated for the treatment of patients with atrial fibrillation and rheumatic heart disease, for the treatment of patients with recent embolic stroke of undetermined source and indirect evidence of cardiac embolism, and in the prevention of vascular-mediated cognitive decline in patients with atrial fibrillation. Multiple clinical trials are assessing the optimal timing of non\u2013vitamin K antagonist oral anticoagulant initiation after a recent ischemic stroke and the benefit:harm ratio of non\u2013vitamin K antagonist oral anticoagulant treatment in patients with atrial fibrillation and history of previous intracranial bleeding. Ongoing trials are addressing the usefulness of left atrial appendage occlusion in both primary and secondary stroke prevention for patients with atrial fibrillation, including those with high risk of bleeding. The additive value of prolonged cardiac monitoring for subclinical atrial fibrillation detection through smartphone applications or implantable cardiac devices, together with the optimal medical management of individuals with covert paroxysmal atrial fibrillation, is a topic of intensive research interest. Colchicine treatment and factor XIa inhibition constitute 2 novel pharmacologic approaches that might provide future treatment options in the secondary prevention of cardioembolic stroke attributable to atrial fibrillation.<\/jats:p>","DOI":"10.1161\/circulationaha.120.049768","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T14:00:23Z","timestamp":1607954423000},"page":"2371-2388","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":99,"title":["Stroke Prevention in Atrial Fibrillation"],"prefix":"10.1161","volume":"142","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6359-0023","authenticated-orcid":true,"given":"Aristeidis H","family":"Katsanos","sequence":"first","affiliation":[{"name":"Division of Neurology, McMaster University and Population Health Research Institute, Hamilton Health Sciences, Canada (A.H.K., R.G.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5745-0307","authenticated-orcid":true,"given":"Hooman","family":"Kamel","sequence":"additional","affiliation":[{"name":"Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medicine, New York (H.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff S.","family":"Healey","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Population Health Research Institute, McMaster University, Hamilton, Canada (J.S.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3210-167X","authenticated-orcid":true,"given":"Robert G.","family":"Hart","sequence":"additional","affiliation":[{"name":"Division of Neurology, McMaster University and Population Health Research Institute, Hamilton Health Sciences, Canada (A.H.K., R.G.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.308407"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.010942"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-018-9005-6"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25700"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07119.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.28.10.973"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.19.2441"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1994.00420130036007"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)92358-Z"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-131-7-199910050-00003"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)62343-0"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/euv421"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.118.011427"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehy136"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1177\/1756285616659411"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.005451"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2020.03.018"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70310-7"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1802686"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1813959"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.119.025168"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1177\/1747493018798554"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.119.028154"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709118"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.035864"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.2984"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.2494"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.0617"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1177\/1747493016681019"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.117.020059"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.009989"},{"key":"e_1_3_2_33_2","unstructured":"Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA). 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