Direct oral anticoagulants versus vitamin K antagonists after recent ischemic stroke in patients with atrial fibrillation
Objective We compared outcomes after treatment with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and a recent cerebral ischemia. Methods We conducted an individual patient data analysis of seven prospective cohort studies. We included...
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| Veröffentlicht in: | Annals of neurology 2019-06, Vol.85 (6), p.823-834 |
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| creator | Seiffge, David J. Paciaroni, Maurizio Wilson, Duncan Koga, Masatoshi Macha, Kosmas Cappellari, Manuel Schaedelin, Sabine Shakeshaft, Clare Takagi, Masahito Tsivgoulis, Georgios Bonetti, Bruno Kallmünzer, Bernd Arihiro, Shoji Alberti, Andrea Polymeris, Alexandros A. Ambler, Gareth Yoshimura, Sohei Venti, Michele Bonati, Leo H. Muir, Keith W. Yamagami, Hiroshi Thilemann, Sebastian Altavilla, Riccardo Peters, Nils Inoue, Manabu Bobinger, Tobias Agnelli, Giancarlo Brown, Martin M. Sato, Shoichiro Acciarresi, Monica Jager, Hans Rolf Bovi, Paolo Schwab, Stefan Lyrer, Philippe Caso, Valeria Toyoda, Kazunori Werring, David J. Engelter, Stefan T. De Marchis, Gian Marco |
| description | Objective
We compared outcomes after treatment with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and a recent cerebral ischemia.
Methods
We conducted an individual patient data analysis of seven prospective cohort studies. We included patients with AF and a recent cerebral ischemia ( |
| doi_str_mv | 10.1002/ana.25489 |
| format | Article |
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We compared outcomes after treatment with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and a recent cerebral ischemia.
Methods
We conducted an individual patient data analysis of seven prospective cohort studies. We included patients with AF and a recent cerebral ischemia (<3 months before starting oral anticoagulation) and a minimum follow‐up of 3 months. We analyzed the association between type of anticoagulation (DOAC versus VKA) with the composite primary endpoint (recurrent ischemic stroke [AIS], intracerebral hemorrhage [ICH], or mortality) using mixed‐effects Cox proportional hazards regression models; we calculated adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs).
Results
We included 4,912 patients (median age, 78 years [interquartile range {IQR}, 71–84]; 2,331 [47.5%] women; median National Institute of Health Stroke Severity Scale at onset, 5 [IQR, 2–12]); 2,256 (45.9%) patients received VKAs and 2,656 (54.1%) DOACs. Median time from index event to starting oral anticoagulation was 5 days (IQR, 2–14) for VKAs and 5 days (IQR, 2–11) for DOACs (p = 0.53). There were 262 acute ischemic strokes (AISs; 4.4%/year), 71 intracranial hemorrrhages (ICHs; 1.2%/year), and 439 deaths (7.4%/year) during the total follow‐up of 5,970 patient‐years. Compared to VKAs, DOAC treatment was associated with reduced risks of the composite endpoint (HR, 0.82; 95% CI, 0.67–1.00; p = 0.05) and ICH (HR, 0.42; 95% CI, 0.24–0.71; p < 0.01); we found no differences for the risk of recurrent AIS (HR, 0.91; 95% CI, 0.70–1.19; p = 0.5) and mortality (HR, 0.83; 95% CI, 0.68–1.03; p = 0.09).
Interpretation
DOAC treatment commenced early after recent cerebral ischemia related to AF was associated with reduced risk of poor clinical outcomes compared to VKA, mainly attributed to lower risks of ICH. ANN NEUROL 2019;85:823–834.</description><identifier>ISSN: 0364-5134</identifier><identifier>EISSN: 1531-8249</identifier><identifier>DOI: 10.1002/ana.25489</identifier><identifier>PMID: 30980560</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Administration, Oral ; Aged ; Aged, 80 and over ; Antagonists ; Anticoagulants ; Anticoagulants - administration & dosage ; Atrial Fibrillation - diagnosis ; Atrial Fibrillation - drug therapy ; Atrial Fibrillation - epidemiology ; Brain Ischemia - diagnosis ; Brain Ischemia - drug therapy ; Brain Ischemia - epidemiology ; Cardiac arrhythmia ; Cohort Studies ; Confidence intervals ; Data analysis ; Female ; Fibrillation ; Follow-Up Studies ; Hazards ; Hemorrhage ; Humans ; Ischemia ; Male ; Mortality ; Patients ; Prospective Studies ; Regression analysis ; Regression models ; Risk factors ; Risk management ; Statistical analysis ; Stroke ; Stroke - diagnosis ; Stroke - drug therapy ; Stroke - epidemiology ; Vitamin K ; Vitamin K - antagonists & inhibitors</subject><ispartof>Annals of neurology, 2019-06, Vol.85 (6), p.823-834</ispartof><rights>2019 The Authors. published by Wiley Periodicals, Inc. on behalf of American Neurological Association.</rights><rights>2019 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.</rights><rights>2019 American Neurological Association</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4439-e9c3188f2d50ab699de5f5036c3c438c8a7474788228f05ac9e9aed1d6eadbeb3</citedby><cites>FETCH-LOGICAL-c4439-e9c3188f2d50ab699de5f5036c3c438c8a7474788228f05ac9e9aed1d6eadbeb3</cites><orcidid>0000-0003-3890-3849 ; 0000-0002-0640-3797 ; 0000-0002-0342-9780</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fana.25489$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fana.25489$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30980560$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Seiffge, David J.</creatorcontrib><creatorcontrib>Paciaroni, Maurizio</creatorcontrib><creatorcontrib>Wilson, Duncan</creatorcontrib><creatorcontrib>Koga, Masatoshi</creatorcontrib><creatorcontrib>Macha, Kosmas</creatorcontrib><creatorcontrib>Cappellari, Manuel</creatorcontrib><creatorcontrib>Schaedelin, Sabine</creatorcontrib><creatorcontrib>Shakeshaft, Clare</creatorcontrib><creatorcontrib>Takagi, Masahito</creatorcontrib><creatorcontrib>Tsivgoulis, Georgios</creatorcontrib><creatorcontrib>Bonetti, Bruno</creatorcontrib><creatorcontrib>Kallmünzer, Bernd</creatorcontrib><creatorcontrib>Arihiro, Shoji</creatorcontrib><creatorcontrib>Alberti, Andrea</creatorcontrib><creatorcontrib>Polymeris, Alexandros A.</creatorcontrib><creatorcontrib>Ambler, Gareth</creatorcontrib><creatorcontrib>Yoshimura, Sohei</creatorcontrib><creatorcontrib>Venti, Michele</creatorcontrib><creatorcontrib>Bonati, Leo H.</creatorcontrib><creatorcontrib>Muir, Keith W.</creatorcontrib><creatorcontrib>Yamagami, Hiroshi</creatorcontrib><creatorcontrib>Thilemann, Sebastian</creatorcontrib><creatorcontrib>Altavilla, Riccardo</creatorcontrib><creatorcontrib>Peters, Nils</creatorcontrib><creatorcontrib>Inoue, Manabu</creatorcontrib><creatorcontrib>Bobinger, Tobias</creatorcontrib><creatorcontrib>Agnelli, Giancarlo</creatorcontrib><creatorcontrib>Brown, Martin M.</creatorcontrib><creatorcontrib>Sato, Shoichiro</creatorcontrib><creatorcontrib>Acciarresi, Monica</creatorcontrib><creatorcontrib>Jager, Hans Rolf</creatorcontrib><creatorcontrib>Bovi, Paolo</creatorcontrib><creatorcontrib>Schwab, Stefan</creatorcontrib><creatorcontrib>Lyrer, Philippe</creatorcontrib><creatorcontrib>Caso, Valeria</creatorcontrib><creatorcontrib>Toyoda, Kazunori</creatorcontrib><creatorcontrib>Werring, David J.</creatorcontrib><creatorcontrib>Engelter, Stefan T.</creatorcontrib><creatorcontrib>De Marchis, Gian Marco</creatorcontrib><creatorcontrib>CROMIS-2, RAF, RAF-DOAC, SAMURAI, NOACISP LONGTERM, Erlangen and Verona registry collaborators</creatorcontrib><creatorcontrib>on behalf of the CROMIS‐2, RAF, RAF‐DOAC, SAMURAI, NOACISP LONGTERM, Erlangen and Verona registry collaborators</creatorcontrib><title>Direct oral anticoagulants versus vitamin K antagonists after recent ischemic stroke in patients with atrial fibrillation</title><title>Annals of neurology</title><addtitle>Ann Neurol</addtitle><description>Objective
We compared outcomes after treatment with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and a recent cerebral ischemia.
Methods
We conducted an individual patient data analysis of seven prospective cohort studies. We included patients with AF and a recent cerebral ischemia (<3 months before starting oral anticoagulation) and a minimum follow‐up of 3 months. We analyzed the association between type of anticoagulation (DOAC versus VKA) with the composite primary endpoint (recurrent ischemic stroke [AIS], intracerebral hemorrhage [ICH], or mortality) using mixed‐effects Cox proportional hazards regression models; we calculated adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs).
Results
We included 4,912 patients (median age, 78 years [interquartile range {IQR}, 71–84]; 2,331 [47.5%] women; median National Institute of Health Stroke Severity Scale at onset, 5 [IQR, 2–12]); 2,256 (45.9%) patients received VKAs and 2,656 (54.1%) DOACs. Median time from index event to starting oral anticoagulation was 5 days (IQR, 2–14) for VKAs and 5 days (IQR, 2–11) for DOACs (p = 0.53). There were 262 acute ischemic strokes (AISs; 4.4%/year), 71 intracranial hemorrrhages (ICHs; 1.2%/year), and 439 deaths (7.4%/year) during the total follow‐up of 5,970 patient‐years. Compared to VKAs, DOAC treatment was associated with reduced risks of the composite endpoint (HR, 0.82; 95% CI, 0.67–1.00; p = 0.05) and ICH (HR, 0.42; 95% CI, 0.24–0.71; p < 0.01); we found no differences for the risk of recurrent AIS (HR, 0.91; 95% CI, 0.70–1.19; p = 0.5) and mortality (HR, 0.83; 95% CI, 0.68–1.03; p = 0.09).
Interpretation
DOAC treatment commenced early after recent cerebral ischemia related to AF was associated with reduced risk of poor clinical outcomes compared to VKA, mainly attributed to lower risks of ICH. ANN NEUROL 2019;85:823–834.</description><subject>Administration, Oral</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antagonists</subject><subject>Anticoagulants</subject><subject>Anticoagulants - administration & dosage</subject><subject>Atrial Fibrillation - diagnosis</subject><subject>Atrial Fibrillation - drug therapy</subject><subject>Atrial Fibrillation - epidemiology</subject><subject>Brain Ischemia - diagnosis</subject><subject>Brain Ischemia - drug therapy</subject><subject>Brain Ischemia - epidemiology</subject><subject>Cardiac arrhythmia</subject><subject>Cohort Studies</subject><subject>Confidence intervals</subject><subject>Data analysis</subject><subject>Female</subject><subject>Fibrillation</subject><subject>Follow-Up Studies</subject><subject>Hazards</subject><subject>Hemorrhage</subject><subject>Humans</subject><subject>Ischemia</subject><subject>Male</subject><subject>Mortality</subject><subject>Patients</subject><subject>Prospective Studies</subject><subject>Regression analysis</subject><subject>Regression models</subject><subject>Risk factors</subject><subject>Risk management</subject><subject>Statistical analysis</subject><subject>Stroke</subject><subject>Stroke - diagnosis</subject><subject>Stroke - drug therapy</subject><subject>Stroke - epidemiology</subject><subject>Vitamin K</subject><subject>Vitamin K - antagonists & inhibitors</subject><issn>0364-5134</issn><issn>1531-8249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp1kUtv1DAUhS0EokNhwR9AkdjAIq3jR8beII3KU61gA2vLcW5mXBJ7sJ1W8-97p1OqglR5YUvn8_E9PoS8buhJQyk7tcGeMCmUfkIWjeRNrZjQT8mC8lbUsuHiiLzI-ZJSqtuGPidHnGpFZUsXZPfRJ3ClismOlQ3Fu2jX84inXF1ByjNuvtjJh-p8r9t1DD6jaIcCqcK7EErls9vA5F2VS4q_oUJ6a4uHvcu1L5vKluTxgcF3yY8jSjG8JM8GO2Z4dbcfk1-fP_08-1pf_Pjy7Wx1UTshuK5BO94oNbBeUtu1WvcgB4nJHHeCK6fsUuBSijE1UGmdBm2hb_oWbN9Bx4_Jh4Pvdu4m6PfzYlazTX6yaWei9eZfJfiNWccr08qWC6HR4N2dQYp_ZsjFTJgXMEaAOGfD2O23Ks0RffsfehnnFDAeUkzwdrnkS6TeHyiXYs4JhvthGmr2hRos1NwWiuybh9Pfk38bROD0AFz7EXaPO5nV99XB8gZQ7q3b</recordid><startdate>201906</startdate><enddate>201906</enddate><creator>Seiffge, David J.</creator><creator>Paciaroni, Maurizio</creator><creator>Wilson, Duncan</creator><creator>Koga, Masatoshi</creator><creator>Macha, Kosmas</creator><creator>Cappellari, Manuel</creator><creator>Schaedelin, Sabine</creator><creator>Shakeshaft, Clare</creator><creator>Takagi, Masahito</creator><creator>Tsivgoulis, Georgios</creator><creator>Bonetti, Bruno</creator><creator>Kallmünzer, Bernd</creator><creator>Arihiro, Shoji</creator><creator>Alberti, Andrea</creator><creator>Polymeris, Alexandros A.</creator><creator>Ambler, Gareth</creator><creator>Yoshimura, Sohei</creator><creator>Venti, Michele</creator><creator>Bonati, Leo H.</creator><creator>Muir, Keith W.</creator><creator>Yamagami, Hiroshi</creator><creator>Thilemann, Sebastian</creator><creator>Altavilla, Riccardo</creator><creator>Peters, Nils</creator><creator>Inoue, Manabu</creator><creator>Bobinger, Tobias</creator><creator>Agnelli, Giancarlo</creator><creator>Brown, Martin M.</creator><creator>Sato, Shoichiro</creator><creator>Acciarresi, Monica</creator><creator>Jager, Hans Rolf</creator><creator>Bovi, Paolo</creator><creator>Schwab, Stefan</creator><creator>Lyrer, Philippe</creator><creator>Caso, Valeria</creator><creator>Toyoda, Kazunori</creator><creator>Werring, David J.</creator><creator>Engelter, Stefan T.</creator><creator>De Marchis, Gian Marco</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-3890-3849</orcidid><orcidid>https://orcid.org/0000-0002-0640-3797</orcidid><orcidid>https://orcid.org/0000-0002-0342-9780</orcidid></search><sort><creationdate>201906</creationdate><title>Direct oral anticoagulants versus vitamin K antagonists after recent ischemic stroke in patients with atrial fibrillation</title><author>Seiffge, David J. ; Paciaroni, Maurizio ; Wilson, Duncan ; Koga, Masatoshi ; Macha, Kosmas ; Cappellari, Manuel ; Schaedelin, Sabine ; Shakeshaft, Clare ; Takagi, Masahito ; Tsivgoulis, Georgios ; Bonetti, Bruno ; Kallmünzer, Bernd ; Arihiro, Shoji ; Alberti, Andrea ; Polymeris, Alexandros A. ; Ambler, Gareth ; Yoshimura, Sohei ; Venti, Michele ; Bonati, Leo H. ; Muir, Keith W. ; Yamagami, Hiroshi ; Thilemann, Sebastian ; Altavilla, Riccardo ; Peters, Nils ; Inoue, Manabu ; Bobinger, Tobias ; Agnelli, Giancarlo ; Brown, Martin M. ; Sato, Shoichiro ; Acciarresi, Monica ; Jager, Hans Rolf ; Bovi, Paolo ; Schwab, Stefan ; Lyrer, Philippe ; Caso, Valeria ; Toyoda, Kazunori ; Werring, David J. ; Engelter, Stefan T. ; De Marchis, Gian Marco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4439-e9c3188f2d50ab699de5f5036c3c438c8a7474788228f05ac9e9aed1d6eadbeb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Administration, Oral</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antagonists</topic><topic>Anticoagulants</topic><topic>Anticoagulants - administration & dosage</topic><topic>Atrial Fibrillation - diagnosis</topic><topic>Atrial Fibrillation - drug therapy</topic><topic>Atrial Fibrillation - epidemiology</topic><topic>Brain Ischemia - diagnosis</topic><topic>Brain Ischemia - drug therapy</topic><topic>Brain Ischemia - epidemiology</topic><topic>Cardiac arrhythmia</topic><topic>Cohort Studies</topic><topic>Confidence intervals</topic><topic>Data analysis</topic><topic>Female</topic><topic>Fibrillation</topic><topic>Follow-Up Studies</topic><topic>Hazards</topic><topic>Hemorrhage</topic><topic>Humans</topic><topic>Ischemia</topic><topic>Male</topic><topic>Mortality</topic><topic>Patients</topic><topic>Prospective Studies</topic><topic>Regression analysis</topic><topic>Regression models</topic><topic>Risk factors</topic><topic>Risk management</topic><topic>Statistical analysis</topic><topic>Stroke</topic><topic>Stroke - diagnosis</topic><topic>Stroke - drug therapy</topic><topic>Stroke - epidemiology</topic><topic>Vitamin K</topic><topic>Vitamin K - antagonists & inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Seiffge, David J.</creatorcontrib><creatorcontrib>Paciaroni, Maurizio</creatorcontrib><creatorcontrib>Wilson, Duncan</creatorcontrib><creatorcontrib>Koga, Masatoshi</creatorcontrib><creatorcontrib>Macha, Kosmas</creatorcontrib><creatorcontrib>Cappellari, Manuel</creatorcontrib><creatorcontrib>Schaedelin, Sabine</creatorcontrib><creatorcontrib>Shakeshaft, Clare</creatorcontrib><creatorcontrib>Takagi, Masahito</creatorcontrib><creatorcontrib>Tsivgoulis, Georgios</creatorcontrib><creatorcontrib>Bonetti, Bruno</creatorcontrib><creatorcontrib>Kallmünzer, Bernd</creatorcontrib><creatorcontrib>Arihiro, Shoji</creatorcontrib><creatorcontrib>Alberti, Andrea</creatorcontrib><creatorcontrib>Polymeris, Alexandros A.</creatorcontrib><creatorcontrib>Ambler, Gareth</creatorcontrib><creatorcontrib>Yoshimura, Sohei</creatorcontrib><creatorcontrib>Venti, Michele</creatorcontrib><creatorcontrib>Bonati, Leo H.</creatorcontrib><creatorcontrib>Muir, Keith W.</creatorcontrib><creatorcontrib>Yamagami, Hiroshi</creatorcontrib><creatorcontrib>Thilemann, Sebastian</creatorcontrib><creatorcontrib>Altavilla, Riccardo</creatorcontrib><creatorcontrib>Peters, Nils</creatorcontrib><creatorcontrib>Inoue, Manabu</creatorcontrib><creatorcontrib>Bobinger, Tobias</creatorcontrib><creatorcontrib>Agnelli, Giancarlo</creatorcontrib><creatorcontrib>Brown, Martin M.</creatorcontrib><creatorcontrib>Sato, Shoichiro</creatorcontrib><creatorcontrib>Acciarresi, Monica</creatorcontrib><creatorcontrib>Jager, Hans Rolf</creatorcontrib><creatorcontrib>Bovi, Paolo</creatorcontrib><creatorcontrib>Schwab, Stefan</creatorcontrib><creatorcontrib>Lyrer, Philippe</creatorcontrib><creatorcontrib>Caso, Valeria</creatorcontrib><creatorcontrib>Toyoda, Kazunori</creatorcontrib><creatorcontrib>Werring, David J.</creatorcontrib><creatorcontrib>Engelter, Stefan T.</creatorcontrib><creatorcontrib>De Marchis, Gian Marco</creatorcontrib><creatorcontrib>CROMIS-2, RAF, RAF-DOAC, SAMURAI, NOACISP LONGTERM, Erlangen and Verona registry collaborators</creatorcontrib><creatorcontrib>on behalf of the CROMIS‐2, RAF, RAF‐DOAC, SAMURAI, NOACISP LONGTERM, Erlangen and Verona registry collaborators</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Annals of neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Seiffge, David J.</au><au>Paciaroni, Maurizio</au><au>Wilson, Duncan</au><au>Koga, Masatoshi</au><au>Macha, Kosmas</au><au>Cappellari, Manuel</au><au>Schaedelin, Sabine</au><au>Shakeshaft, Clare</au><au>Takagi, Masahito</au><au>Tsivgoulis, Georgios</au><au>Bonetti, Bruno</au><au>Kallmünzer, Bernd</au><au>Arihiro, Shoji</au><au>Alberti, Andrea</au><au>Polymeris, Alexandros A.</au><au>Ambler, Gareth</au><au>Yoshimura, Sohei</au><au>Venti, Michele</au><au>Bonati, Leo H.</au><au>Muir, Keith W.</au><au>Yamagami, Hiroshi</au><au>Thilemann, Sebastian</au><au>Altavilla, Riccardo</au><au>Peters, Nils</au><au>Inoue, Manabu</au><au>Bobinger, Tobias</au><au>Agnelli, Giancarlo</au><au>Brown, Martin M.</au><au>Sato, Shoichiro</au><au>Acciarresi, Monica</au><au>Jager, Hans Rolf</au><au>Bovi, Paolo</au><au>Schwab, Stefan</au><au>Lyrer, Philippe</au><au>Caso, Valeria</au><au>Toyoda, Kazunori</au><au>Werring, David J.</au><au>Engelter, Stefan T.</au><au>De Marchis, Gian Marco</au><aucorp>CROMIS-2, RAF, RAF-DOAC, SAMURAI, NOACISP LONGTERM, Erlangen and Verona registry collaborators</aucorp><aucorp>on behalf of the CROMIS‐2, RAF, RAF‐DOAC, SAMURAI, NOACISP LONGTERM, Erlangen and Verona registry collaborators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Direct oral anticoagulants versus vitamin K antagonists after recent ischemic stroke in patients with atrial fibrillation</atitle><jtitle>Annals of neurology</jtitle><addtitle>Ann Neurol</addtitle><date>2019-06</date><risdate>2019</risdate><volume>85</volume><issue>6</issue><spage>823</spage><epage>834</epage><pages>823-834</pages><issn>0364-5134</issn><eissn>1531-8249</eissn><abstract>Objective
We compared outcomes after treatment with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and a recent cerebral ischemia.
Methods
We conducted an individual patient data analysis of seven prospective cohort studies. We included patients with AF and a recent cerebral ischemia (<3 months before starting oral anticoagulation) and a minimum follow‐up of 3 months. We analyzed the association between type of anticoagulation (DOAC versus VKA) with the composite primary endpoint (recurrent ischemic stroke [AIS], intracerebral hemorrhage [ICH], or mortality) using mixed‐effects Cox proportional hazards regression models; we calculated adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs).
Results
We included 4,912 patients (median age, 78 years [interquartile range {IQR}, 71–84]; 2,331 [47.5%] women; median National Institute of Health Stroke Severity Scale at onset, 5 [IQR, 2–12]); 2,256 (45.9%) patients received VKAs and 2,656 (54.1%) DOACs. Median time from index event to starting oral anticoagulation was 5 days (IQR, 2–14) for VKAs and 5 days (IQR, 2–11) for DOACs (p = 0.53). There were 262 acute ischemic strokes (AISs; 4.4%/year), 71 intracranial hemorrrhages (ICHs; 1.2%/year), and 439 deaths (7.4%/year) during the total follow‐up of 5,970 patient‐years. Compared to VKAs, DOAC treatment was associated with reduced risks of the composite endpoint (HR, 0.82; 95% CI, 0.67–1.00; p = 0.05) and ICH (HR, 0.42; 95% CI, 0.24–0.71; p < 0.01); we found no differences for the risk of recurrent AIS (HR, 0.91; 95% CI, 0.70–1.19; p = 0.5) and mortality (HR, 0.83; 95% CI, 0.68–1.03; p = 0.09).
Interpretation
DOAC treatment commenced early after recent cerebral ischemia related to AF was associated with reduced risk of poor clinical outcomes compared to VKA, mainly attributed to lower risks of ICH. ANN NEUROL 2019;85:823–834.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>30980560</pmid><doi>10.1002/ana.25489</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-3890-3849</orcidid><orcidid>https://orcid.org/0000-0002-0640-3797</orcidid><orcidid>https://orcid.org/0000-0002-0342-9780</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0364-5134 |
| ispartof | Annals of neurology, 2019-06, Vol.85 (6), p.823-834 |
| issn | 0364-5134 1531-8249 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6563449 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Administration, Oral Aged Aged, 80 and over Antagonists Anticoagulants Anticoagulants - administration & dosage Atrial Fibrillation - diagnosis Atrial Fibrillation - drug therapy Atrial Fibrillation - epidemiology Brain Ischemia - diagnosis Brain Ischemia - drug therapy Brain Ischemia - epidemiology Cardiac arrhythmia Cohort Studies Confidence intervals Data analysis Female Fibrillation Follow-Up Studies Hazards Hemorrhage Humans Ischemia Male Mortality Patients Prospective Studies Regression analysis Regression models Risk factors Risk management Statistical analysis Stroke Stroke - diagnosis Stroke - drug therapy Stroke - epidemiology Vitamin K Vitamin K - antagonists & inhibitors |
| title | Direct oral anticoagulants versus vitamin K antagonists after recent ischemic stroke in patients with atrial fibrillation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T06%3A56%3A25IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Direct%20oral%20anticoagulants%20versus%20vitamin%20K%20antagonists%20after%20recent%20ischemic%20stroke%20in%20patients%20with%20atrial%20fibrillation&rft.jtitle=Annals%20of%20neurology&rft.au=Seiffge,%20David%20J.&rft.aucorp=CROMIS-2,%20RAF,%20RAF-DOAC,%20SAMURAI,%20NOACISP%20LONGTERM,%20Erlangen%20and%20Verona%20registry%20collaborators&rft.date=2019-06&rft.volume=85&rft.issue=6&rft.spage=823&rft.epage=834&rft.pages=823-834&rft.issn=0364-5134&rft.eissn=1531-8249&rft_id=info:doi/10.1002/ana.25489&rft_dat=%3Cproquest_pubme%3E2209610893%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2224367737&rft_id=info:pmid/30980560&rfr_iscdi=true |