Early Versus Late Initiation of Direct Oral Anticoagulants After Ischemic Stroke in People With Atrial Fibrillation and Hemorrhagic Transformation: Prespecified Subanalysis of the Randomized Controlled ELAN Trial-Reference-Cited by-同舟云学术

Early Versus Late Initiation of Direct Oral Anticoagulants After Ischemic Stroke in People With Atrial Fibrillation and Hemorrhagic Transformation: Prespecified Subanalysis of the Randomized Controlled ELAN Trial

Published:2024-07-02 Issue:1 Volume:150 Page:19-29
ISSN:0009-7322
Container-title:Circulation
language:en
Short-container-title:Circulation

Author:

Rohner Roman¹^ORCID,Kneihsl Markus²³⁴^ORCID,Goeldlin Martina B.⁵^ORCID,Hakim Arsany¹^ORCID,Branca Mattia⁶^ORCID,Abend Stefanie⁵⁶^ORCID,Valenzuela Pinilla Waldo⁷^ORCID,Fenzl Sabine¹,Rezny-Kasprzak Beata¹,Strbian Daniel⁸^ORCID,Trelle Sven^ORCID,Paciaroni Maurizio⁹^ORCID,Thomalla Götz¹⁰^ORCID,Michel Patrik¹¹^ORCID,Nedeltchev Krassen¹²,Gattringer Thomas²³^ORCID,Sandset Else C.¹³^ORCID,Bonati Leo⁴¹⁴^ORCID,Aguiar de Sousa Diana¹⁵^ORCID,Sylaja P.N.¹⁶^ORCID,Ntaios George¹⁷^ORCID,Koga Masatoshi¹⁸^ORCID,Gdovinova Zuzana¹⁹^ORCID,Lemmens Robin²⁰^ORCID,Bornstein Natan M.²¹^ORCID,Kelly Peter²²^ORCID,Katan Mira⁴^ORCID,Horvath Thomas⁵,Dawson Jesse²³^ORCID,Fischer Urs⁵⁴^ORCID,

Affiliation:

1. University Institute of Diagnostic and Interventional Neuroradiology (R.R., A.H., S.F., B.R.-K.), Inselspital Bern University Hospital and University of Bern, Switzerland.

2. Department of Neurology (M. Kneihsl, T.G.), Medical University of Graz, Austria.

3. Department of Radiology, Division of Neuroradiology, Vascular and Interventional Radiology (M. Kneihsl, T.G.), Medical University of Graz, Austria.

4. Department of Neurology, University and University Hospital Basel, Switzerland (M. Kneihsl, L.B., M. Katan, U.F.).

5. Department of Neurology (M.B.G., S.A., T.H., U.F.), Inselspital Bern University Hospital and University of Bern, Switzerland.

6. Department of Clinical Research, University of Bern, Switzerland (M.B., S.T.).

7. Support Center for Advanced Neuroimaging (W.V.P.), Inselspital Bern University Hospital and University of Bern, Switzerland.

8. Department of Neurology, Helsinki University Hospital, and University of Helsinki, Finland (D.S.).

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

10. Department of Neurology, University Medical Center Hamburg–Eppendorf, Germany (G.T.).

11. Department of Neurology, University Hospital Lausanne, University of Lausanne, Switzerland (P.M.).

12. Department of Neurology, Cantonal Hospital Aarau, Switzerland (K.N.).

13. Department of Neurology, Oslo University Hospital, Norway (E.C.S.).

14. Research Department, Reha Rheinfelden, Switzerland (L.B.).

15. Stroke Center, Lisbon Central University Hospital and Faculdade de Medicina, Universidade de Lisboa, Portugal (D.A.d.S.).

16. Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India (P.N.S.).

17. Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece (G.N.).

18. Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan (M. Koga).

19. Department of Neurology, P.J. Safarik University, Faculty of Medicine and University Hospital L. Pasteur Kosice, Slovakia (Z.G.).

20. KU Leuven, Department of Neurosciences, Experimental Neurology; University Hospitals Leuven, Department of Neurology, Belgium (R.L.).

21. Department of Neurology, Shaare-Zedek Medical Center, Jerusalem, Israel (N.M.B.).

22. Stroke Clinical Trials Network Ireland, University College Dublin/Department of Neurology, Mater University Hospital (P.K.).

23. School of Cardiovascular and Metabolic Health, Queen Elizabeth University Hospital, University of Glasgow, UK (J.D.).

Abstract

BACKGROUND: Whether hemorrhagic transformation (HT) modifies the treatment effect of early compared with late initiation of direct oral anticoagulation in people with ischemic stroke and atrial fibrillation is unknown. METHODS: This is a post hoc analysis of the ELAN trial (Early Versus Late Initiation of Direct Oral Anticoagulants in Post-Ischaemic Stroke Patients With Atrial Fibrillation). The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, major extracranial bleeding, systemic embolism, or vascular death within 30 days. Secondary outcomes were the individual components, 30- and 90-day functional outcome. We estimated outcomes based on HT, subclassified as hemorrhagic infarction (HI) or parenchymal hemorrhage (PH) on prerandomization imaging (core laboratory rating) using adjusted risk differences between treatment arms. RESULTS: Overall, 247 of 1970 participants (12.5%) had HT (114 HI 1, 77 HI 2, 34 PH 1, 22 PH 2). For the primary outcome, the estimated adjusted risk difference (early versus late) was −2.2% (95% CI, −7.8% to 3.5%) in people with HT (HI: −4.7% [95% CI, −10.8% to 1.4%]; PH: 6.1% [95% CI, −8.5% to 20.6%]) and −0.9% (95% CI, −2.6% to 0.8%) in people without HT. Numbers of symptomatic intracranial hemorrhage were identical in people with and without HT. With early treatment, the estimated adjusted risk difference for poor 90-day functional outcome (modified Rankin Scale score, 3–6) was 11.5% (95% CI, −0.8% to 23.8%) in participants with HT (HI: 7.4% [95% CI, −6.4% to 21.2%]; PH: 25.1% [95% CI, 0.2% to 50.0%]) and −2.6% (95% CI, −7.1% to 1.8%) in people without HT. CONCLUSIONS: We found no evidence of major treatment effect heterogeneity or safety concerns with early compared with late direct oral anticoagulation initiation in people with and without HT. However, early direct oral anticoagulation initiation may worsen functional outcomes in people with PH. REGISTRATION: URL: http://www.clinicaltrials.gov ; Unique identifier: NCT03148457.

Funder

Swiss National Science Foundation

Schweizerische Herzstiftung

Stroke Association in the United Kingdom

Intramural Research Fund for Cardiovascular Diseases of the National Cerebral and Cardiovascular Center

Swiss Academy of Medical Sciences/Bangerter-Rhyner Foundation

Publisher

Ovid Technologies (Wolters Kluwer Health)

Reference25 articles.

1. Hemorrhagic Transformation Within 36 Hours of a Cerebral Infarct

2. Hemorrhagic Transformation in Acute Ischemic Stroke: A Quantitative Systematic Review

3. Early recurrent embolism associated with nonvalvular atrial fibrillation: a retrospective study.

4. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association

5. Early Anticoagulation in Patients with Acute Ischemic Stroke Due to Atrial Fibrillation: A Systematic Review and Meta-Analysis

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1. Correction to: Early Versus Late Initiation of Direct Oral Anticoagulants After Ischemic Stroke in People With Atrial Fibrillation and Hemorrhagic Transformation: Prespecified Subanalysis of the Randomized Controlled ELAN Trial;Circulation;2024-07-02