Anticoagulation Timing in Cardioembolic Stroke and Recurrent Event Risk

Objective Guidelines recommend initiating anticoagulation within 4 to 14 days after cardioembolic stroke. Data supporting this did not account for key factors potentially affecting the decision to initiate anticoagulation, such as infarct size, hemorrhagic transformation, or high‐risk features on ec...

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Published in	Annals of neurology Vol. 88; no. 4; pp. 807 - 816
Main Authors	Yaghi, Shadi, Trivedi, Tushar, Henninger, Nils, Giles, James, Liu, Angela, Nagy, Muhammad, Kaushal, Ashutosh, Azher, Idrees, Mac Grory, Brian, Fakhri, Hiba, Brown Espaillat, Kiersten, Asad, Syed Daniyal, Pasupuleti, Hemanth, Martin, Heather, Tan, Jose, Veerasamy, Manivannan, Liberman, Ava L., Esenwa, Charles, Cheng, Natalie, Moncrieffe, Khadean, Moeini‐Naghani, Iman, Siddu, Mithilesh, Scher, Erica, Leon Guerrero, Christopher R., Khan, Muhib, Nouh, Amre, Mistry, Eva, Keyrouz, Salah, Furie, Karen
Format	Journal Article
Language	English
Published	Hoboken, USA John Wiley & Sons, Inc 01.10.2020 Wiley Subscription Services, Inc
Subjects	Aged Aged, 80 and over Anticoagulants Anticoagulants - administration & dosage Anticoagulants - adverse effects Brain Ischemia - epidemiology Cerebral Hemorrhage - epidemiology Clinical trials Confidence intervals Echocardiography Embolic Stroke - complications Embolic Stroke - drug therapy Embolism Female Fibrillation Health risks Hemorrhage Humans Ischemia Male Middle Aged Recurrence Retrospective Studies Risk Factors Stroke Time Factors Transient ischemic attack
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ISSN	0364-5134 1531-8249 1531-8249
DOI	10.1002/ana.25844

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Abstract	Objective Guidelines recommend initiating anticoagulation within 4 to 14 days after cardioembolic stroke. Data supporting this did not account for key factors potentially affecting the decision to initiate anticoagulation, such as infarct size, hemorrhagic transformation, or high‐risk features on echocardiography. Methods We pooled data from stroke registries of 8 comprehensive stroke centers across the United States. We included consecutive patients admitted with ischemic stroke and atrial fibrillation. The primary predictor was timing of initiating anticoagulation (0–3 days, 4–14 days, or >14 days), and outcomes were recurrent stroke/transient ischemic attack/systemic embolism, symptomatic intracerebral hemorrhage (sICH), and major extracranial hemorrhage (ECH) within 90 days. Results Among 2,084 patients, 1,289 met the inclusion criteria. The combined endpoint occurred in 10.1% (n = 130) subjects (87 ischemic events, 20 sICH, and 29 ECH). Overall, there was no significant difference in the composite endpoint between the 3 groups (0–3 days: 10.3%, 64/617; 4–14 days: 9.7%, 52/535; >14 days: 10.2%, 14/137; p = 0.933). In adjusted models, patients started on anticoagulation between 4 and 14 days did not have a lower rate of sICH (vs 0–3 days; odds ratio [OR] = 1.49, 95% confidence interval [CI] = 0.50–4.43), nor did they have a lower rate of recurrent ischemic events (vs >14 days; OR = 0.76, 95% CI = 0.36–1.62, p = 0.482). Interpretation In this multicenter real‐world cohort, the recommended (4–14 days) time frame to start oral anticoagulation was not associated with reduced ischemic and hemorrhagic outcomes. Randomized trials are required to determine the optimal timing of anticoagulation initiation. ANN NEUROL 2020;88:807–816
AbstractList	Objective Guidelines recommend initiating anticoagulation within 4 to 14 days after cardioembolic stroke. Data supporting this did not account for key factors potentially affecting the decision to initiate anticoagulation, such as infarct size, hemorrhagic transformation, or high‐risk features on echocardiography. Methods We pooled data from stroke registries of 8 comprehensive stroke centers across the United States. We included consecutive patients admitted with ischemic stroke and atrial fibrillation. The primary predictor was timing of initiating anticoagulation (0–3 days, 4–14 days, or >14 days), and outcomes were recurrent stroke/transient ischemic attack/systemic embolism, symptomatic intracerebral hemorrhage (sICH), and major extracranial hemorrhage (ECH) within 90 days. Results Among 2,084 patients, 1,289 met the inclusion criteria. The combined endpoint occurred in 10.1% (n = 130) subjects (87 ischemic events, 20 sICH, and 29 ECH). Overall, there was no significant difference in the composite endpoint between the 3 groups (0–3 days: 10.3%, 64/617; 4–14 days: 9.7%, 52/535; >14 days: 10.2%, 14/137; p = 0.933). In adjusted models, patients started on anticoagulation between 4 and 14 days did not have a lower rate of sICH (vs 0–3 days; odds ratio [OR] = 1.49, 95% confidence interval [CI] = 0.50–4.43), nor did they have a lower rate of recurrent ischemic events (vs >14 days; OR = 0.76, 95% CI = 0.36–1.62, p = 0.482). Interpretation In this multicenter real‐world cohort, the recommended (4–14 days) time frame to start oral anticoagulation was not associated with reduced ischemic and hemorrhagic outcomes. Randomized trials are required to determine the optimal timing of anticoagulation initiation. ANN NEUROL 2020;88:807–816 Guidelines recommend initiating anticoagulation within 4 to 14 days after cardioembolic stroke. Data supporting this did not account for key factors potentially affecting the decision to initiate anticoagulation, such as infarct size, hemorrhagic transformation, or high-risk features on echocardiography.OBJECTIVEGuidelines recommend initiating anticoagulation within 4 to 14 days after cardioembolic stroke. Data supporting this did not account for key factors potentially affecting the decision to initiate anticoagulation, such as infarct size, hemorrhagic transformation, or high-risk features on echocardiography.We pooled data from stroke registries of 8 comprehensive stroke centers across the United States. We included consecutive patients admitted with ischemic stroke and atrial fibrillation. The primary predictor was timing of initiating anticoagulation (0-3 days, 4-14 days, or >14 days), and outcomes were recurrent stroke/transient ischemic attack/systemic embolism, symptomatic intracerebral hemorrhage (sICH), and major extracranial hemorrhage (ECH) within 90 days.METHODSWe pooled data from stroke registries of 8 comprehensive stroke centers across the United States. We included consecutive patients admitted with ischemic stroke and atrial fibrillation. The primary predictor was timing of initiating anticoagulation (0-3 days, 4-14 days, or >14 days), and outcomes were recurrent stroke/transient ischemic attack/systemic embolism, symptomatic intracerebral hemorrhage (sICH), and major extracranial hemorrhage (ECH) within 90 days.Among 2,084 patients, 1,289 met the inclusion criteria. The combined endpoint occurred in 10.1% (n = 130) subjects (87 ischemic events, 20 sICH, and 29 ECH). Overall, there was no significant difference in the composite endpoint between the 3 groups (0-3 days: 10.3%, 64/617; 4-14 days: 9.7%, 52/535; >14 days: 10.2%, 14/137; p = 0.933). In adjusted models, patients started on anticoagulation between 4 and 14 days did not have a lower rate of sICH (vs 0-3 days; odds ratio [OR] = 1.49, 95% confidence interval [CI] = 0.50-4.43), nor did they have a lower rate of recurrent ischemic events (vs >14 days; OR = 0.76, 95% CI = 0.36-1.62, p = 0.482).RESULTSAmong 2,084 patients, 1,289 met the inclusion criteria. The combined endpoint occurred in 10.1% (n = 130) subjects (87 ischemic events, 20 sICH, and 29 ECH). Overall, there was no significant difference in the composite endpoint between the 3 groups (0-3 days: 10.3%, 64/617; 4-14 days: 9.7%, 52/535; >14 days: 10.2%, 14/137; p = 0.933). In adjusted models, patients started on anticoagulation between 4 and 14 days did not have a lower rate of sICH (vs 0-3 days; odds ratio [OR] = 1.49, 95% confidence interval [CI] = 0.50-4.43), nor did they have a lower rate of recurrent ischemic events (vs >14 days; OR = 0.76, 95% CI = 0.36-1.62, p = 0.482).In this multicenter real-world cohort, the recommended (4-14 days) time frame to start oral anticoagulation was not associated with reduced ischemic and hemorrhagic outcomes. Randomized trials are required to determine the optimal timing of anticoagulation initiation. ANN NEUROL 2020;88:807-816.INTERPRETATIONIn this multicenter real-world cohort, the recommended (4-14 days) time frame to start oral anticoagulation was not associated with reduced ischemic and hemorrhagic outcomes. Randomized trials are required to determine the optimal timing of anticoagulation initiation. ANN NEUROL 2020;88:807-816. Guidelines recommend initiating anticoagulation within 4 to 14 days after cardioembolic stroke. Data supporting this did not account for key factors potentially affecting the decision to initiate anticoagulation, such as infarct size, hemorrhagic transformation, or high-risk features on echocardiography. We pooled data from stroke registries of 8 comprehensive stroke centers across the United States. We included consecutive patients admitted with ischemic stroke and atrial fibrillation. The primary predictor was timing of initiating anticoagulation (0-3 days, 4-14 days, or >14 days), and outcomes were recurrent stroke/transient ischemic attack/systemic embolism, symptomatic intracerebral hemorrhage (sICH), and major extracranial hemorrhage (ECH) within 90 days. Among 2,084 patients, 1,289 met the inclusion criteria. The combined endpoint occurred in 10.1% (n = 130) subjects (87 ischemic events, 20 sICH, and 29 ECH). Overall, there was no significant difference in the composite endpoint between the 3 groups (0-3 days: 10.3%, 64/617; 4-14 days: 9.7%, 52/535; >14 days: 10.2%, 14/137; p = 0.933). In adjusted models, patients started on anticoagulation between 4 and 14 days did not have a lower rate of sICH (vs 0-3 days; odds ratio [OR] = 1.49, 95% confidence interval [CI] = 0.50-4.43), nor did they have a lower rate of recurrent ischemic events (vs >14 days; OR = 0.76, 95% CI = 0.36-1.62, p = 0.482). In this multicenter real-world cohort, the recommended (4-14 days) time frame to start oral anticoagulation was not associated with reduced ischemic and hemorrhagic outcomes. Randomized trials are required to determine the optimal timing of anticoagulation initiation. ANN NEUROL 2020;88:807-816. ObjectiveGuidelines recommend initiating anticoagulation within 4 to 14 days after cardioembolic stroke. Data supporting this did not account for key factors potentially affecting the decision to initiate anticoagulation, such as infarct size, hemorrhagic transformation, or high‐risk features on echocardiography.MethodsWe pooled data from stroke registries of 8 comprehensive stroke centers across the United States. We included consecutive patients admitted with ischemic stroke and atrial fibrillation. The primary predictor was timing of initiating anticoagulation (0–3 days, 4–14 days, or >14 days), and outcomes were recurrent stroke/transient ischemic attack/systemic embolism, symptomatic intracerebral hemorrhage (sICH), and major extracranial hemorrhage (ECH) within 90 days.ResultsAmong 2,084 patients, 1,289 met the inclusion criteria. The combined endpoint occurred in 10.1% (n = 130) subjects (87 ischemic events, 20 sICH, and 29 ECH). Overall, there was no significant difference in the composite endpoint between the 3 groups (0–3 days: 10.3%, 64/617; 4–14 days: 9.7%, 52/535; >14 days: 10.2%, 14/137; p = 0.933). In adjusted models, patients started on anticoagulation between 4 and 14 days did not have a lower rate of sICH (vs 0–3 days; odds ratio [OR] = 1.49, 95% confidence interval [CI] = 0.50–4.43), nor did they have a lower rate of recurrent ischemic events (vs >14 days; OR = 0.76, 95% CI = 0.36–1.62, p = 0.482).InterpretationIn this multicenter real‐world cohort, the recommended (4–14 days) time frame to start oral anticoagulation was not associated with reduced ischemic and hemorrhagic outcomes. Randomized trials are required to determine the optimal timing of anticoagulation initiation. ANN NEUROL 2020;88:807–816
Author	Tan, Jose Siddu, Mithilesh Trivedi, Tushar Moncrieffe, Khadean Nagy, Muhammad Pasupuleti, Hemanth Mac Grory, Brian Esenwa, Charles Nouh, Amre Yaghi, Shadi Veerasamy, Manivannan Martin, Heather Brown Espaillat, Kiersten Azher, Idrees Liu, Angela Furie, Karen Leon Guerrero, Christopher R. Keyrouz, Salah Cheng, Natalie Fakhri, Hiba Moeini‐Naghani, Iman Mistry, Eva Scher, Erica Asad, Syed Daniyal Giles, James Liberman, Ava L. Khan, Muhib Henninger, Nils Kaushal, Ashutosh
AuthorAffiliation	2 Department of Neurology, University of Massachusetts, Worcester, MA 10 Department of Neurology, George Washington University, Washington, DC 4 Department of Neurology, Washington University, Saint Louis, MO 6 Department of Neurology, Vanderbilt University, Nashville, TN 3 Department of Psychiatry, University of Massachusetts, Worcester, MA 5 Department of Neurology, Brown University, Providence, RI 7 Department of Neurology, Hartford Hospital, Hartford, CT 9 Department of Neurology, Montefiore Medical Center, New York, NY 1 Department of Neurology, New York Langone Health, New York, NY 8 Department of Neurology, Spectrum Health, Grand Rapids, MI
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Heparin in Acute Embolic Stroke Trial publication-title: Lancet – ident: e_1_2_9_17_1 doi: 10.1161/STROKEAHA.117.017084 – ident: e_1_2_9_3_1 doi: 10.1055/s-0037-1603465 – ident: e_1_2_9_15_1 doi: 10.1093/eurheartj/ehr488 – ident: e_1_2_9_11_1 doi: 10.1212/WNL.0000000000003283 – ident: e_1_2_9_12_1 doi: 10.1212/WNL.0b013e3181aa5329 – ident: e_1_2_9_21_1 doi: 10.1002/ana.25489 – ident: e_1_2_9_6_1 doi: 10.1016/S0140-6736(97)04011-7 – ident: e_1_2_9_5_1 doi: 10.1016/S0140-6736(00)02085-7 – ident: e_1_2_9_14_1 doi: 10.1212/WNL.28.10.973 – ident: e_1_2_9_20_1 doi: 10.1161/STROKEAHA.116.015770 – ident: e_1_2_9_23_1 doi: 10.1007/s11883-019-0790-x – ident: e_1_2_9_7_1 doi: 10.1161/STR.0000000000000158 – ident: e_1_2_9_2_1 doi: 10.1161/CIRCRESAHA.116.308407 – ident: e_1_2_9_10_1 doi: 10.1136/jnnp-2018-318890 – ident: e_1_2_9_16_1 doi: 10.1016/0735-1097(94)90662-9 – ident: e_1_2_9_13_1 doi: 10.1161/STR.0000000000000152 – ident: e_1_2_9_4_1 doi: 10.1001/jama.279.16.1265 – ident: e_1_2_9_9_1 doi: 10.1016/S1474-4422(18)30356-9 – ident: e_1_2_9_19_1 doi: 10.1136/neurintsurg-2018-013848 – ident: e_1_2_9_18_1 doi: 10.1161/STROKEAHA.118.022856 – ident: e_1_2_9_8_1 doi: 10.1161/STROKEAHA.115.008891 – ident: e_1_2_9_22_1 doi: 10.1161/JAHA.117.007034
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Snippet	Objective Guidelines recommend initiating anticoagulation within 4 to 14 days after cardioembolic stroke. Data supporting this did not account for key factors... Guidelines recommend initiating anticoagulation within 4 to 14 days after cardioembolic stroke. Data supporting this did not account for key factors... ObjectiveGuidelines recommend initiating anticoagulation within 4 to 14 days after cardioembolic stroke. Data supporting this did not account for key factors...
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SubjectTerms	Aged Aged, 80 and over Anticoagulants Anticoagulants - administration & dosage Anticoagulants - adverse effects Brain Ischemia - epidemiology Cerebral Hemorrhage - epidemiology Clinical trials Confidence intervals Echocardiography Embolic Stroke - complications Embolic Stroke - drug therapy Embolism Female Fibrillation Health risks Hemorrhage Humans Ischemia Male Middle Aged Recurrence Retrospective Studies Risk Factors Stroke Time Factors Transient ischemic attack
Title	Anticoagulation Timing in Cardioembolic Stroke and Recurrent Event Risk
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