Apixaban to Prevent Recurrence After Cryptogenic Stroke in Patients With Atrial Cardiopathy
Author:
Kamel Hooman1, Longstreth W. T.234, Tirschwell David L.2, Kronmal Richard A.5, Marshall Randolph S.6, Broderick Joseph P.7, Aragón García Rebeca6, Plummer Pamela7, Sabagha Noor7, Pauls Qi8, Cassarly Christy8, Dillon Catherine R.8, Di Tullio Marco R.9, Hod Eldad A.10, Soliman Elsayed Z.11, Gladstone David J.12, Healey Jeff S.13, Sharma Mukul13, Chaturvedi Seemant14, Janis L. Scott15, Krishnaiah Balaji16, Nahab Fadi17, Kasner Scott E.18, Stanton Robert J.7, Kleindorfer Dawn O.19, Starr Matthew20, Winder Toni R.21, Clark Wayne M.22, Miller Benjamin R.23, Elkind Mitchell S. V.624, , Asaithambi Ganesh25, Klaiman Maxwell25, Malhotra Konark25, Fetter Mary25, Wanahita Anna25, Merritt Stacie25, Sajjad Rehan25, McPolin Kate25, Coull Bruce25, Kavathia Shriya25, Kolikonda Murali25, Calhoun Sara25, de los Rios la Rosa Felipe25, Del Conde Ian25, Elysée Josette25, Aghaebrahim Amin25, Stratoberdha Melissa25, Ford Andria25, Giles James25, Wang Yan25, Babka Jennifer25, Damani Rahul25, Gutierrez-Flores Barbara25, Kumar Sandeep25, Marchina Sarah25, Swerdloff Marc25, Scott Margaret25, Sangha Amandeep25, Patterson Kelly25, Shulman Julie25, Feske Steven25, Rafael Romero Jose25, Aparicio Hugo25, Greer David25, Stafford Rebecca25, Tamayo Arturo25, Anderson Leanne25, Smirnakis Stelios25, Rademaker Quinn25, Hourihane Maurice25, Sawyer Robert25, Ching Marilou25, Kandel Amit25, Magun Rakesh25, Crumlish Annemarie25, Bosco Annaliese25, Singh Sanjay25, Singh Abhishek25, Traynor Elizabeth25, Sankaraneni Ram25, Haddad. Toufik25, Isder Carly25, Rasmussen Lois25, Rochestie Dustin25, Brunetti Nancy25, Pandya Dhruvil25, Baligod Rosemarie25, Capampangan Dan25, Sahelian Allegra25, Nomura Jason25, Gannon Kimberly25, Raser-Schramm Jonathan25, Murphy Kathleen25, Itrat Ahmed25, Hudock Debra25, Wisco Dolora25, Sweeney Laura25, Likosky William25, Garcia Rebekah25, Schumacher Hermann25, Colman Lindsey25, Lisle Benjamin25, Atkinson Uriah25, Aude Wady25, Trevino Cassandra25, Attenhoffer Kevin25, Fortiche Claudia25, Rajamani Kumar25, Reyes Amanda25, Arshad Hasnain25, Weidman Julie25, Adamczyk Peter25, Galvez Leah25, Nahab Fadi25, Frankel Michael25, Escobar Alicia25, Schindler Kiva25, Schultz Megan25, Bhadsavle Lori25, Craft Leah25, Mackey Ariane25, Verreault Steve25, Camden Marie-Christine25, Gosselin-Lefebvre Stéphanie25, Lavoie Suzy25, Patel Nirav25, Bailey Richard25, Lazzaro Marc25, Cierny Marek25, Helms Ann25, Moore Caitlin25, Book Diane25, Attar Hatim25, Morse Tiffany25, Aboagye Sophia25, Coleman Lakiesha25, Alter-Troilo Katie25, Short Rodney25, Weakley Desyree25, Wold Jana25, Aitken Kinga25, Sachdev Harmeet25, Paulson Audrey25, Bianchi Nicolas25, Ng Kelvin25, Ratnayake Kanchana25, Tirschwell David25, Asirot Mary25, Kunze Allison25, Hou Yan25, Patel Reena25, Greiner Laura25, Miller Benjamin25, Scherber Julie25, Katramados Angelos25, Wiegand Teresa25, Kasner Scott25, Burdett Rebecca25, Cucchiara Brett25, Messe Steven25, Yuan Qingyang25, Kurowski George Donna25, Witsch Jens25, Stein Laura25, Favilla Christopher25, Siegler James25, Thon Jesse25, Mullen Michael25, Rothstein Aaron25, Khaazal Ossama25, Cristancho Daniel25, Grodinsky Emily25, Khan Farhan25, Renner Christopher25, Zuflacht Jonah25, Humbert Kelley25, Kumar Arooshi25, Dawod Judy25, Kone Gbambele25, Reyes-Esteves Sahily25, Kvantaliani Nino25, De Santo Mary Liz25, Gallatti Nichole25, Keating Devin25, Concha Mauricio25, Pannell Robynn25, Murray Nick25, Anderson Jacki25, Bosh Lindsay25, Marulanda-Londono Erika25, Escobar Andrea25, Ajani Zahra25, Gonzalez Nathalie25, Neil William25, Fechter Michael25, Sanossian Nerses25, Pena Jesus25, Binley Clare25, Elamin Elsadig25, GEREIN Meghan25, Law Susan25, Tita Monique25, Jalini Shirin25, Nguyen Andrew25, Sehgal Siddharth25, Culbertson Collin25, Ou Penhleakhena25, Kirchhoffer Kaitlyn25, Cross Danielle25, Kruse Louise25, Gizzi Martin25, Kummer Karla25, Yacoub Hussam25, Orzel Andrew25, Azhar Salman25, Elsaadany Ronnie25, Sposato Luciano25, Mandzia Jennifer25, Mai Lauren25, Khaw Alexander25, Fridman Sebastian25, Beauchamp Beth25, Lambourn Lindsay25, Ramezan-Arab Nima25, Caballero Deysi25, Omidvar Omid25, Thompson Michael25, Altamirano Melanie25, Pundik Svetlana25, Double Manda25, Bentho Oladi25, Streib Christopher25, Affan Muhammad25, Hussein Haitham25, McCullough-Hicks Margy25, Hariharan Praveen25, Solei Amelia25, Bard Kate25, Weller Amanda25, Miller Kathleen25, Brauch Anna25, Lawyer Chloe25, Quigley Deb25, Staugaitis Abbey25, Wang Qingliang25, Mootoo Maryna25, Singhal Aneesh25, Carr Rhianna25, Rabinstein Alejandro25, Scharf Eugene25, Headlee Amy25, Lin Michelle25, McDonald Meredith25, Reid Taylor25, Majjhoo Aniel25, Marci Roberts25, Rayes Mahmoud25, Paschall Emily25, Meisel Karl25, Shaw Colleen25, Stemer Andrew25, Waldon Emma25, Hsia Amie25, Kalaria Chandni25, Burton Shannon25, Kim Yongwoo25, Somani Sana25, Craft Veronica25, Smith Jamal25, Matthews Juby25, Grainger Megan25, Anderson Cassidy25, Holmstedt Christine25, Lematty Caitlan25, Sharrief Anjail25, Cooksey Gabretta25, Alderazi Yazan25, Tremont Chad25, Maidan Lucian25, Hornbuckle Danielle25, Zaidat Osama25, Upham Cynthia25, Krishnaiah Balaji25, Alexandrov Andrei25, Elangovan Cheran25, Rubin Mark25, Thacker Quentin25, Hanna Joseph25, Cook Dana25, Jacobs Bradley25, Weller Christina25, Kirchoff-Torres Kathryn25, Springer Mellanie25, Moncrieffe Khadean25, Islam Tanzina25, Sethi Pramod25, Ahmed Jamil25, Rudolph Steven25, Morhaim Holly25, Brockington Carolyn25, Poondla Naresh25, Hansen Calvin25, Banker Heather25, Naqvi Imama25, Miller Eliza25, Castillo Carmen25, Aragon Garcia Rebeca25, Slane Kevin25, Parikh Neal25, Navi Babak25, Mir Saad25, Segal Alan25, White Halina25, Liberman Ava25, Leifer Dana25, Kamel Hooman25, Sherman Carla25, Kaiser Jed25, Liao Vanessa25, LeMoss Natalie25, Lansdale Kelsey25, Lord Aaron25, Cotrina Maria25, Torres Jose25, Anganoo-Khan Danika25, Winder Toni25, Elliot Jill25, Atalay Yahya25, Stathis Courtney25, Katz Jeffrey25, Schwartz Erin25, Stanton Kayla25, Anghel Sandra25, Ballout Ahmad25, Dee Alicia25, Modaber Morteza25, Patel Neisha25, Arora Rohan25, Teron Ina25, Libman Richard25, Pasram Kirendra25, Caprio Fan25, Vincent Rachel25, Talkad Arun25, Ravisankar Ashwath25, Zha Alicia25, Hamed Mohammad25, SIdorov Evgeny25, Samkutty Danny25, Gordon David25, Hamilton Robert25, Velez Faddi25, King Jason25, Ray Bappaditya25, Vaughn April25, Hill Blair25, Sharps Jason25, Zweifler Richard25, Henry Jessica25, Clark Wayne25, Bozorgchami Hormozd25, Miller Parker25, Laursen Rachel25, Amin Sonesh25, Pattle Megan25, Foley Jon25, Dolan Monica25, Nagle Emilie25, Zortea Paulo25, Leonard Reilly25, Sen Souvik25, Kodumuri Nishanth25, Lowe Justin25, Logue Makenzie25, Kabetso Amanda25, Fleming Phil25, White Corey25, Gates Damon25, Towfighi Amytis25, Ayala-Rivera Monica25, Guisado Raul25, De La Cuest Karen25, Pyle Maria25, Burton Tina25, Furie Karen25, Yaghi Shadi25, Kala Narendra25, Schomer Ashley25, Moody Scott25, Chaudhry Deepica25, Elizardo Catrina25, Vora Nirav25, Groezinger Katy25, Mehta Deviyani25, Moccio Michelle25, Stenroos Edward25, Saver Jeffrey25, Mercado Daisy25, Graham Brett25, Hunter Gary25, Peeling Lissa25, Kelly Michael25, Cooley Regan25, Wasyliw Sanchea25, Tyson Cassandra25, Junk Emily25, Foster Kaitlyn25, Bolt Kala25, Urroz Lilian25, Whelan Ruth25, Gardner Aaron25, Bhavsar Shrijal25, Cherian Laurel25, Conners James25, Song Sarah25, Dafer Rima25, Vargas Alejandro25, McCoy Henna25, Olds Karin25, Summers Debbie25, Colorado Rene25, Nielsen Terri25, Morales Juan25, Hemphill Claude25, Randazzo Dominica25, Spaeth Destini25, Neal Jason25, Zdroik Melissa25, Modir Royya25, McQuaid Theresa25, Cheng Yu25, Murphy Cary25, Manassarians Henrik25, Siddiqui Fazeel25, Reiser Laura25, Khan Muhib25, Taylor Heidi25, Mueller Stephanie25, Khoury Naim25, Bainter Lauren25, Kaur Supreet25, Calzadillas Guadalupe25, Edgell Randall25, Cummins Benjamin25, McDaneld Logan25, Bertrand Lisa25, Matmati Kelly25, Matmati Nabil25, Vora Nirali25, Garcia Madelleine25, Spence David25, Mabb Tisha25, Benesch Curtis25, Prentiss Emily25, Hopyan Julia25, Gladstone David25, Fatakdawala Idris25, Mittal Manoj25, Donnel Tammy25, Lenakakis Dawn25, Gelinas Katharyn25, Bennett Alicia25, Burgin William25, Hairston Marla25, Katz Paul25, Reimer Hannah25, Salem Rony25, Stern Tracy25, Dharia Robin25, Paglione Sasha25, Goshgarian Christopher25, Smith Stacy25, Melkumova Emiliya25, Melkumyan Nikolas25, Onteddu Sanjeeva25, Richardson Lisa25, Shafie Mohammad25, Yu Wengui25, Fong Julia25, Prado Josue25, Rapp Karen25, Smith Wade25, Wilson Christina25, May Neringa25, Sundararajan Sophia25, Andrews Mary25, Goddeau Richard25, Silver Brian25, Manxhari Christina25, Demers-Peel Meaghan25, Kenmuir Cynthia25, Kerfoot Kristen25, Ireland Christy25, Starr Matthew25, Shang Ty25, Johnson Mark25, Jones Erica25, Gebreyohannas Mehari25, Clark Jessica25, Southerlandc Andrew25, Worrallc Bradford25, Gusler Matthew25, JohnsonN Keri25, Roach Necrisha25, Chapman Sherita25, Solenski Nina25, Bhole Rohini25, Sohail Amna25, Johnston Karen25, Weko Andrew25, Perch Miah25, Batton Cheyenne25, Ramsey Allison25, Gunter Sonya25, Monita Jane25, Meyer Marie25, Murwin Jennifer25, Lundell Kaitlin25, Essa Nimco25, Lyerly Michael25, Davis Tammy25, Shuaib Ashfaq25, Piquette Lori25, Hill Michael25, Coutts Shelagh25, Save Supriya25, Ryckborst Karla25, Kenney Carol25, Toussaint Lana25, Brorson James25, Coleman Elisheva25, Hall Emma25, Stanton Robert25, Kleindorfer Dawn25, Demel Stacie25, Powers Jennifer25, Testai Fernando25, Hillmann Maureen25, Leira Enrique25, Olalde Heena25, Kawano-Castillo Jorge25, Pendurthi Aparna25, Houghton Margaret25, Moore Justin25, Maruthanal Joel25, Fugate Alissa25, Das Saurav25, Pettigrew Creed25, Arnold Pattricia25, Ander Tracy25, Jerde Ann25, Chaturvedi Seemant25, Spadafora Christina25, Carrera Joseph25, Becker Christopher25, Brown Devin25, Burke James25, Conyers Frank25, Harrington Anthony25, Hill Christopher25, Roberts Jessica25, Johnson Patty25, Shekhar Shashank25, Gangadhara Shreyas25, Smith Margaret25, Fayad Pierre25, Obaro Helen25, Girotra Tarun25, Morales Jacqueline25, Rael Erin25, Saleemi Muhammad-Adeel25, Sugg Rebecca25, Grissett Tamekia25, White Stefanie25, Behrouz Reza25, Richardson Jody25, Chung Lee25, Majersik Jennifer25, DeWitt Dana25, Lyden Stephanie25, Reddy Vivek25, Tekiela Peter25, Hannon Peter25, de Havenon Adam25, Marcus Brian25, Hoversten Knut25, Meyer Chelsea25, Ruff Jerdan25, Rock Theodore25, Dela Cruz Michael25, Bradbury Edward25, Bock Jenna25, Call Kevin25, McQuivey Ryan25, Belanger Karen25, Huffer Andrew25, McRae Sharon25, Hassan Ameer25, Khan Raza25, Sanchez Olive25, Field Thalia25, Wilson Laura25, Gorman John25, Van Gaal Stephen25, Yip Samuel25, Teal Philip25, Benavente Oscar25, Mann Sharanpal25, King-Azote Princess25, Maclean Genoveva25, Ma Carson25, Villaluna Karina25, Froehler Michael25, Rajpal Hemangi25, Alvi Muhammad25, Dobrzynski Sara25, Sherman Jay25, Bushnell Cheryl25, Schmidt Krystal25, Wallis Roi25, Panizzon Kimberly25, Narula Reshma25, Kuohn Lindsey25, Jasak Sara25, Kampp Michael25, Pish Melissa25
Affiliation:
1. Clinical and Translational Neuroscience Unit, Department of Neurology and Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York 2. Department of Neurology, University of Washington, Seattle 3. Department of Medicine, University of Washington, Seattle 4. Department of Epidemiology, University of Washington, Seattle 5. Department of Biostatistics, University of Washington, Seattle 6. Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York 7. Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 8. Department of Public Health Sciences, Medical University of South Carolina, Charleston 9. Division of Cardiology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York 10. Department of Pathology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York 11. Epidemiological Cardiology Research Center, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina 12. Sunnybrook Research Institute, Hurvitz Brain Sciences Program, Sunnybrook Health Sciences Centre, and Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada 13. Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada 14. Department of Neurology, University of Maryland, and Baltimore VA Hospital, Baltimore 15. National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 16. Department of Neurology, University of Tennessee Health Sciences Center, Memphis 17. Departments of Neurology and Pediatrics, Emory University, Atlanta, Georgia 18. Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia 19. Department of Neurology, University of Michigan, Ann Arbor 20. Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 21. Neurologic Research Center, Lethbridge, Alberta, Canada 22. Department of Neurology, Oregon Health & Science University, Portland 23. Department of Neurology, University of Minnesota, Minneapolis 24. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York 25. for the ARCADIA Investigators
Abstract
ImportanceAtrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation.ObjectiveTo compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy.Design, Setting, and ParticipantsMulticenter, double-blind, phase 3 randomized clinical trial of 1015 participants with cryptogenic stroke and evidence of atrial cardiopathy, defined as P-wave terminal force greater than 5000 μV × ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250 pg/mL, or left atrial diameter index of 3 cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomization. Enrollment and follow-up occurred from February 1, 2018, through February 28, 2023, at 185 sites in the National Institutes of Health StrokeNet and the Canadian Stroke Consortium.InterventionsApixaban, 5 mg or 2.5 mg, twice daily (n = 507) vs aspirin, 81 mg, once daily (n = 508).Main Outcomes and MeasuresThe primary efficacy outcome in a time-to-event analysis was recurrent stroke. All participants, including those diagnosed with atrial fibrillation after randomization, were analyzed according to the groups to which they were randomized. The primary safety outcomes were symptomatic intracranial hemorrhage and other major hemorrhage.ResultsWith 1015 of the target 1100 participants enrolled and mean follow-up of 1.8 years, the trial was stopped for futility after a planned interim analysis. The mean (SD) age of participants was 68.0 (11.0) years, 54.3% were female, and 87.5% completed the full duration of follow-up. Recurrent stroke occurred in 40 patients in the apixaban group (annualized rate, 4.4%) and 40 patients in the aspirin group (annualized rate, 4.4%) (hazard ratio, 1.00 [95% CI, 0.64-1.55]). Symptomatic intracranial hemorrhage occurred in 0 patients taking apixaban and 7 patients taking aspirin (annualized rate, 1.1%). Other major hemorrhages occurred in 5 patients taking apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (hazard ratio, 1.02 [95% CI, 0.29-3.52]).Conclusions and RelevanceIn patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin.Trial RegistrationClinicalTrials.gov Identifier: NCT03192215
Publisher
American Medical Association (AMA)
Cited by
32 articles.
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