. 2019 Feb;14(2):207-214.

doi: 10.1177/1747493018799981. Epub 2018 Sep 10.

The AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic stroke randomized trial: Rationale and methods

Hooman Kamel¹, W T Longstreth Jr^{2

3

4}, David L Tirschwell², Richard A Kronmal⁵, Joseph P Broderick⁶, Yuko Y Palesch⁷, Caitlyn Meinzer⁷, Catherine Dillon⁷, Irene Ewing⁶, Judith A Spilker⁶, Marco R Di Tullio⁸, Eldad A Hod⁹, Elsayed Z Soliman¹⁰, Seemant Chaturvedi¹¹, Claudia S Moy¹², Scott Janis¹², Mitchell Sv Elkind^{13

14}

Affiliations

¹ 1 Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medical College, New York, NY, USA.
² 2 Department of Neurology, University of Washington, Seattle, WA, USA.
³ 3 Department of Medicine, University of Washington, Seattle, WA, USA.
⁴ 4 Department of Epidemiology, University of Washington, Seattle, WA, USA.
⁵ 5 Department of Biostatistics, University of Washington, Seattle, WA.
⁶ 6 Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
⁷ 7 Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
⁸ 8 Department of Medicine, Columbia University, New York, NY, USA.
⁹ 9 Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.
¹⁰ 10 Epidemiological Cardiology Research Center, Department of Epidemiology and Prevention, and Department of Internal Medicine, Section on Cardiology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
¹¹ 11 Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA.
¹² 12 National Institutes of Neurological Disease and Stroke, Bethesda, MD, USA.
¹³ 13 Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
¹⁴ 14 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.

PMID: 30196789
PMCID: PMC6645380
DOI: 10.1177/1747493018799981

The AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic stroke randomized trial: Rationale and methods

Hooman Kamel et al. Int J Stroke. 2019 Feb.

. 2019 Feb;14(2):207-214.

doi: 10.1177/1747493018799981. Epub 2018 Sep 10.

Authors

Affiliations

¹ 1 Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medical College, New York, NY, USA.
² 2 Department of Neurology, University of Washington, Seattle, WA, USA.
³ 3 Department of Medicine, University of Washington, Seattle, WA, USA.
⁴ 4 Department of Epidemiology, University of Washington, Seattle, WA, USA.
⁵ 5 Department of Biostatistics, University of Washington, Seattle, WA.
⁶ 6 Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
⁷ 7 Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
⁸ 8 Department of Medicine, Columbia University, New York, NY, USA.
⁹ 9 Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.
¹⁰ 10 Epidemiological Cardiology Research Center, Department of Epidemiology and Prevention, and Department of Internal Medicine, Section on Cardiology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
¹¹ 11 Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA.
¹² 12 National Institutes of Neurological Disease and Stroke, Bethesda, MD, USA.
¹³ 13 Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
¹⁴ 14 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.

PMID: 30196789
PMCID: PMC6645380
DOI: 10.1177/1747493018799981

Abstract

Rationale: Recent data suggest that a thrombogenic atrial substrate can cause stroke in the absence of atrial fibrillation. Such an atrial cardiopathy may explain some proportion of cryptogenic strokes.

Aims: The aim of the ARCADIA trial is to test the hypothesis that apixaban is superior to aspirin for the prevention of recurrent stroke in subjects with cryptogenic ischemic stroke and atrial cardiopathy.

Sample size estimate: 1100 participants.

Methods and design: Biomarker-driven, randomized, double-blind, active-control, phase 3 clinical trial conducted at 120 U.S. centers participating in NIH StrokeNet.

Population studied: Patients ≥ 45 years of age with embolic stroke of undetermined source and evidence of atrial cardiopathy, defined as ≥ 1 of the following markers: P-wave terminal force >5000 µV × ms in ECG lead V₁, serum NT-proBNP > 250 pg/mL, and left atrial diameter index ≥ 3 cm/m² on echocardiogram. Exclusion criteria include any atrial fibrillation, a definite indication or contraindication to antiplatelet or anticoagulant therapy, or a clinically significant bleeding diathesis. Intervention: Apixaban 5 mg twice daily versus aspirin 81 mg once daily. Analysis: Survival analysis and the log-rank test will be used to compare treatment groups according to the intention-to-treat principle, including participants who require open-label anticoagulation for newly detected atrial fibrillation.

Study outcomes: The primary efficacy outcome is recurrent stroke of any type. The primary safety outcomes are symptomatic intracranial hemorrhage and major hemorrhage other than intracranial hemorrhage.

Discussion: ARCADIA is the first trial to test whether anticoagulant therapy reduces stroke recurrence in patients with atrial cardiopathy but no known atrial fibrillation.

Keywords: Clinical trial; apixaban; aspirin; atrial cardiomyopathy; atrial cardiopathy; atrial myopathy; cryptogenic stroke; ischemic stroke.

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Conflict of interest statement

Declaration of Conflicting Interests

Dr. Elkind receives compensation for providing consultative services for Abbott, Biotelemetry/Cardionet, Boehringer-Ingelheim, and Sanofi-Regeneron Partnership; receives study medication and laboratory support in kind but no personal compensation from the BMS-Pfizer Alliance for Eliquis® and Roche for the ARCADIA trial; receives royalties from UpToDate for a chapter related to cryptogenic stroke; and serves on the National, Founders Affiliate, and New York City chapter boards of the American Heart Association/American Stroke Association. Dr. Elkind’s institution, Columbia University, receives compensation through a service agreement with Medtronic for Dr. Elkind’s effort on clinical trials related to cardiac monitoring in stroke patients. No other authors report conflicts of interest.

References

1. Hart RG, Catanese L, Perera KS, Ntaios G, Connolly SJ. Embolic stroke of undetermined source: a systematic review and clinical update. Stroke. 2017;48:867–872. - PubMed
1. Hart RG, Diener HC, Coutts SB, Easton JD, Granger CB, O’Donnell MJ, et al. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol. 2014;13:429–438. - PubMed
1. Sanna T, Diener HC, Passman RS, Di Lazzaro V, Bernstein RA, Morillo CA, et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med. 2014;370:2478–2486. - PubMed
1. Alpert MA, Munuswamy K. Electrocardiographic diagnosis of left atrial enlargement. Arch Intern Med. 1989;149:1161–1165. - PubMed
1. Goyal SB, Spodick DH. Electromechanical dysfunction of the left atrium associated with interatrial block. Am Heart J. 2001;142:823–827. - PubMed

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The AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic stroke randomized trial: Rationale and methods

Affiliations

The AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic stroke randomized trial: Rationale and methods

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

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Grants and funding

LinkOut - more resources

Full Text Sources

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Medical

Research Materials