Early vs Late Anticoagulation in Minor, Moderate, and Major Ischemic Stroke With Atrial Fibrillation-Reference-Cited by-同舟云学术

Early vs Late Anticoagulation in Minor, Moderate, and Major Ischemic Stroke With Atrial Fibrillation

Published:2024-07-01 Issue:7 Volume:81 Page:693
ISSN:2168-6149
Container-title:JAMA Neurology
language:en
Short-container-title:JAMA Neurol

Author:

Goeldlin Martina B.¹,Hakim Arsany²,Branca Mattia³,Abend Stefanie¹,Kneihsl Markus¹⁴⁵⁶,Valenzuela Pinilla Waldo⁷,Fenzl Sabine²,Rezny-Kasprzak Beata²,Rohner Roman²,Strbian Daniel⁸,Paciaroni Maurizio⁹,Thomalla Goetz¹⁰,Michel Patrik¹¹,Nedeltchev Krassen¹¹²,Gattringer Thomas⁵⁶,Sandset Else Charlotte¹³,Bonati Leo⁴¹⁴,Aguiar de Sousa Diana¹⁵¹⁶,Sylaja P. N.¹⁷,Ntaios George¹⁸,Koga Masatoshi¹⁹,Gdovinova Zuzana²⁰²¹,Lemmens Robin²²²³,Bornstein Natan M.²⁴,Kelly Peter²⁵,Katan Mira⁴,Horvath Thomas¹,Dawson Jesse²⁶,Fischer Urs¹⁴, ,Adeyemi Adedolapo Kamaldee²⁷,Vedamurthy Adhiyaman²⁷,Scutelnic Adrian²⁷,Hisanao Akiyama²⁷,Wilson Alastair²⁷,Tarnutzer Alexander Andrea²⁷,Pichler Alexander²⁷,Salerno Alexander²⁷,Vanhoorne Alexander²⁷,Polymeris Alexandros²⁷,Wilkinson Ami²⁷,Paiva Nunes Ana²⁷,Adamou Anastasia²⁷,Peeters André²⁷,Humm Andrea M.²⁷,Zini Andrea²⁷,Dhasan Aneesh²⁷,Alonso Angelika²⁷,Fischer Anna²⁷,Saukkonen Anna Maija²⁷,Müller Anna²⁷,Berberich Anne²⁷,Falcou Anne²⁷,Devroye Annemie²⁷,Hostens Arne²⁷,Liesz Arthur²⁷,Annamalai Arunkumar²⁷,Sharma Arvind Vijaysharan²⁷,Paliantonis Asterios²⁷,Nallasivan Aumugam²⁷,Abdul-Rahim Azmil²⁷,Grimshaw Ben²⁷,Kallmünzer Bernd²⁷,Rodic Biljana²⁷,Clarke Brian²⁷,Menezes Brian²⁷,Weder Bruno J.²⁷,Ciobanu Carla²⁷,Cereda Carlo W.²⁷,Loos Caroline²⁷,Kulyk Caterina²⁷,Gonçalves Martins Catia²⁷,Ferrari Cecilia²⁷,Fung Christian²⁷,Caporale Christina²⁷,McAlpine Christine²⁷,Globas Christoph²⁷,Gumbinger Christoph²⁷,Bonvin Christophe²⁷,Krogias Christos²⁷,Whyte Clare ²⁷,Bassetti Claudio²⁷,Ryan Dan²⁷,Charissé Daniel²⁷,Richter Daniel²⁷,Schrammel Daniel²⁷,Giudici Daria²⁷,Nabavi Darius G.²⁷,Bradley David²⁷,Orion David²⁷,Seiffge David J.²⁷,Werring David²⁷,Strambo Davide²⁷,Esson Derek²⁷,Khurana Dheeraj²⁷,Melancia Diana²⁷,Staykov Dimitre²⁷,Hemelsoet Dimitri²⁷,Michalski Dominik²⁷,Schlemm Eckhard²⁷,Karagkiozi Efstathia²⁷,Saxhaug Kristoffersen Espen²⁷,Marcelis Evelyn²⁷,Wright Fiona²⁷,Delvoye François²⁷,Medlin Friedrich²⁷,Takayuki Fukano²⁷,Sirimarco Gaia²⁷,Shim Gek²⁷,Smith Gemma Marie²⁷,Royl Georg ²⁷,Pope George²⁷,Salanti Georgia²⁷,Sibolt Gerli²⁷,Guzman-Gutierrez German²⁷,De Marchis Gian Marco²⁷,Bianco Giovanni²⁷,Dymond Harvey²⁷,Ihle-Hansen Hege²⁷,Thomas Helen²⁷,Stetefeld Henning R.²⁷,Koundal Himanshu²⁷,Asaf Honig²⁷,Anwar Ijaz²⁷,De Magistris Ilaria Leone²⁷,Noone Imelda²⁷,Olave Bersas Ingrid²⁷,Muresan Ioan-Paul²⁷,Vanpanteghem Isabelle²⁷,Gralla Jan²⁷,Vynckier Jan²⁷,Demeestere Jelle²⁷,Offermann Jens²⁷,Pandian Jeyaraj Durai²⁷,Sousa João André²⁷,Marto João Pedro²⁷,Sargento-Freitas João²⁷,Vehoff Jochen²⁷,Pelz Johann²⁷,McCabe John J.²⁷,Harbison Joseph²⁷,Mbroh Joshua²⁷,Wagner Judith²⁷,Niederhauser Julien²⁷,Sipilä Jussi²⁷,Tanaka Kanta²⁷,Rani Karthika²⁷,Klimcikova Katarina²⁷,Smith Kerry²⁷,Soltesova Klaudia²⁷,Macha Kosmas²⁷,Matzusono Kosuke²⁷,Szabo Kristina²⁷,Yperzeele Laetitia²⁷,Alteheld Lars²⁷,Kellert Lars²⁷,Healy Liam²⁷,Zhang Liqun²⁷,Fisch Loraine²⁷,Gentile Luana²⁷,Schelosky Ludwig²⁷,Kellermair Lukas²⁷,Gbadamosh Lukuman ²⁷,Dixon Lynn²⁷,Nakajima Makoto²⁷,Inoue Manabu²⁷,Krishnan Manju²⁷,Bolognese Manuel²⁷,Arnold Marcel²⁷,Mosconi Maria Giulia²⁷,Altmann Marianne²⁷,Lang Marie²⁷,Psychogios Marios²⁷,Tiainen Marjaana²⁷,Barber Mark²⁷,Arnold Markus²⁷,Magriço Marta²⁷,Müller Martin²⁷,Joan MacLeod Mary²⁷,Greulich Matthias²⁷,Rutgers Matthieu Pierre²⁷,Schell Maximilian²⁷,Garcia-Pons Melissa ²⁷,Pøhner Skahjem Mette²⁷,Haley Michael²⁷,Marnane Michael²⁷,Vosko Milan²⁷,Katan Mira²⁷,Mako Miroslav²⁷,Polavarapu Naren²⁷,Martinez-Majander Nicolas²⁷,Del Gaudio Nicole²⁷,Caracciolo Nicoletta G.²⁷,Peters Nils²⁷,Mahajan Niranjan²⁷,Silimon Norbert²⁷,Onur Oezguer A.²⁷,Olbert Elisabeth²⁷,Morten Rønning Ole²⁷,Kelly Peter²⁷,Ringleb Peter²⁷,Slade Peter²⁷,Vanacker Peter²⁷,Desfontaines Philippe²⁷,Nair Priya²⁷,Marian Rados²⁷,Parthasarathy Rajsrinivas²⁷,Hidalgo Rea²⁷,Mulcahy Riona²⁷,Kato Risa²⁷,Bhatia Rohit²⁷,Collins Ronan²⁷,Leker Ronen R.²⁷,Eichel Roni²⁷,Tanaka Ryota²⁷,Hussayni Husseini Samer Al²⁷,Clarke Sandra²⁷,Sreedharan Sapna Erat²⁷,Ostanek Sarah²⁷,Amina Sellimi²⁷,Beyeler Seraina²⁷,Storton Sharon²⁷,Fujimoto Shigeru²⁷,Räty Silja²⁷,Fandler-Höfler Simon²⁷,Galego Sofia²⁷,Yoshimura Sohei²⁷,Matsubara Soichiro²⁷,Greisenegger Stefan²⁷,Oberndorfer Stefan²⁷,Ray Sucharita²⁷,Renaud Susanne²⁷,Riebau Susanne²⁷,Poli Sven²⁷,Politz Svetlana²⁷,Albert Sylvan J.²⁷,Kunieda Takenobu²⁷,Sato Takeo²⁷,Yoshimoto Takeshi²⁷,Anjum Tal²⁷,Pap Tatjana²⁷,Costa Telma²⁷,Pinho e Melo Teresa²⁷,Iype Thomas²⁷,Cassidy Tim²⁷,Von Oertzen Tim J.²⁷,Kahles Timo²⁷,Danilo Toni²⁷,Spetalen Torstein²⁷,Tatlisumak Turgut²⁷,De Herdt Veerle²⁷,Borisova Victoria²⁷,Pamidimukkala Vijaya²⁷,Huded Vikram²⁷,Gupta Vipul²⁷,Kumar Vishav²⁷,Nambiar Vivek²⁷,Pfeilschifter Waltraud²⁷,Stoop Wendy²⁷,Iguchi Yasuyuki²⁷,Müller Seljeseth Yngve²⁷,Abousleiman Youssif²⁷,Yakushiji Yusuke²⁷,Pencz Zoltan²⁷

Affiliation:

1. Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

2. University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

3. Clinical Trials Unit, University of Bern, Bern, Switzerland

4. Department of Neurology, University of Basel and University Hospital Basel, Basel, Switzerland

5. Department of Neurology, Medical University of Graz, Graz, Austria

6. Division of Neuroradiology, Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria

7. Support Center for Advanced Neuroimaging, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland

8. Department of Neurology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland

9. Internal, Vascular, and Emergency Medicine, Stroke Unit, Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy

10. Department of Neurology, University Medical Center Hamburg–Eppendorf, Hamburg, Germany

11. Department of Neurology, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland

12. Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland

13. Department of Neurology, Oslo University Hospital, Oslo, Norway

14. Research Department, Reha Rheinfelden, Rheinfelden, Switzerland

15. Stroke Center, Lisbon Central University Hospital, Lisbon, Portugal

16. Faculty of Medicine, Institute of Anatomy, University of Lisbon, Lisbon, Portugal

17. Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India

18. Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece

19. Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan

20. Department of Neurology, Pavol Jozef Šafárik University, Košice, Slovakia

21. Faculty of Medicine, Louis Pasteur University Hospital, Košice, Slovakia

22. Department of Neurosciences, Experimental Neurology, KU Leuven, Leuven, Belgium

23. Department of Neurology, University Hospitals Leuven, Leuven, Belgium

24. Department of Neurology, Shaare-Zedek Medical Center, Jerusalem, Israel

25. Stroke Clinical Trials Network Ireland, School of Medicine, University College Dublin and Department of Neurology, Mater University Hospital, Dublin, Ireland

26. School of Cardiovascular and Metabolic Health, Queen Elizabeth University Hospital, University of Glasgow, Glasgow, United Kingdom

27. for the ELAN Investigators

Abstract

ImportanceWhether infarct size modifies the treatment effect of early vs late direct oral anticoagulant (DOAC) initiation in people with ischemic stroke and atrial fibrillation is unknown.ObjectiveTo assess whether infarct size modifies the safety and efficacy of early vs late DOAC initiation.Design, Setting, and ParticipantsPost hoc analysis of participants from the multinational (&gt;100 sites in 15 countries) randomized clinical Early Versus Later Anticoagulation for Stroke With Atrial Fibrillation (ELAN) trial who had (1) acute ischemic stroke, (2) atrial fibrillation, and (3) brain imaging available before randomization. The ELAN trial was conducted between October 2017 and December 2022. Data were analyzed from October to December 2023 for this post hoc analysis.InterventionEarly vs late DOAC initiation after ischemic stroke. Early DOAC initiation was within 48 hours for minor or moderate stroke or on days 6 to 7 for major stroke; late DOAC initiation was on days 3 to 4 for minor stroke, days 6 to 7 for moderate stroke, and days 12 to 14 for major stroke.Main Outcomes and MeasuresThe primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, extracranial bleeding, systemic embolism, or vascular death within 30 days. The outcome was assessed according to infarct size (minor, moderate, or major) using odds ratios and risk differences between treatment arms. Interrater reliability for infarct size between the core laboratory and local raters was assessed, and whether this modified the estimated treatment effects was also examined.ResultsA total of 1962 of the original 2013 participants (909 [46.3%] female; median [IQR] age, 77 [70-84] years) were included. The primary outcome occurred in 10 of 371 participants (2.7%) with early DOAC initiation vs 11 of 364 (3.0%) with late DOAC initiation among those with minor stroke (odds ratio [OR], 0.89; 95% CI, 0.38-2.10); in 11 of 388 (2.8%) with early DOAC initiation vs 14 of 392 (3.6%) with late DOAC initiation among those with moderate stroke (OR, 0.80; 95% CI, 0.35-1.74); and in 8 of 219 (3.7%) with early DOAC initiation vs 16 of 228 (7.0%) with late DOAC initiation among those with major stroke (OR, 0.52; 95% CI, 0.21-1.18). The 95% CI for the estimated risk difference of the primary outcome in early anticoagulation was −2.78% to 2.12% for minor stroke, −3.23% to 1.76% for moderate stroke, and −7.49% to 0.81% for major stroke. There was no significant treatment interaction for the primary outcome. For infarct size, interrater reliability was moderate (κ = 0.675; 95% CI, 0.647-0.702) for local vs core laboratory raters and strong (κ = 0.875; 95% CI, 0.855-0.894) between core laboratory raters.Conclusions and RelevanceThe treatment effect of early DOAC initiation did not differ in people with minor, moderate, or major stroke assessed by brain imaging. Early treatment was not associated with a higher rate of adverse events, especially symptomatic intracranial hemorrhage, for any infarct size, including major stroke.Trial RegistrationClinicalTrials.gov Identifier: NCT03148457

Publisher

American Medical Association (AMA)

Link

https://jamanetwork.com/journals/jamaneurology/articlepdf/2819377/jamaneurology_goeldlin_2024_oi_240029_1719343648.34429.pdf

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