Early versus Later Anticoagulation for Stroke with Atrial Fibrillation.

Fischer U, Koga M, Strbian D, Branca M, Abend S, Trelle S, Paciaroni M, Thomalla G, Michel P, Nedeltchev K, Bonati LH, Ntaios G, Gattringer T, Sandset EC, Kelly P, Lemmens R, Sylaja PN, Aguiar De Sousa D, Bornstein NM, Gdovinova Z, Yoshimoto T, Tiainen M, Thomas H, Krishnan M, Shim GC, Gumbinger C, Vehoff J, Zhang L, Matsuzono K, Kristoffersen E, Desfontaines P, Vanacker P, Alonso A, Yakushiji Y, Kulyk C, Hemelsoet D, Poli S, Paiva Nunes A, Caracciolo N, Slade P, Demeestere J, Salerno A, Kneihsl M, Kahles T, Giudici D, Tanaka K, Räty S, Hidalgo R, Werring DJ, Göldlin M, Arnold M, Ferrari C, Beyeler S, Fung C, Weder BJ, Tatlisumak T, Fenzl S, Rezny-Kasprzak B, Hakim A, Salanti G, Bassetti C, Gralla J, Seiffge DJ, Horvath T, Dawson J (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Book Volume: 388

Pages Range: 2411-2421

Journal Issue: 26

DOI: 10.1056/NEJMoa2303048

Abstract

BACKGROUND: The effect of early as compared with later initiation of direct oral anticoagulants (DOACs) in persons with atrial fibrillation who have had an acute ischemic stroke is unclear. METHODS: We performed an investigator-initiated, open-label trial at 103 sites in 15 countries. Participants were randomly assigned in a 1:1 ratio to early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). Assessors were unaware of the trial-group assignments. The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the components of the composite primary outcome at 30 and 90 days. RESULTS: Of 2013 participants (37% with minor stroke, 40% with moderate stroke, and 23% with major stroke), 1006 were assigned to early anticoagulation and 1007 to later anticoagulation. A primary-outcome event occurred in 29 participants (2.9%) in the early-treatment group and 41 participants (4.1%) in the later-treatment group (risk difference, -1.18 percentage points; 95% confidence interval [CI], -2.84 to 0.47) by 30 days. Recurrent ischemic stroke occurred in 14 participants (1.4%) in the early-treatment group and 25 participants (2.5%) in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29 to 1.07) by 30 days and in 18 participants (1.9%) and 30 participants (3.1%), respectively, by 90 days (odds ratio, 0.60; 95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 2 participants (0.2%) in both groups by 30 days. CONCLUSIONS: In this trial, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95% confidence interval) with early than with later use of DOACs. (Funded by the Swiss National Science Foundation and others; ELAN ClinicalTrials.gov number, NCT03148457.).

Additional Organisation(s)

Involved external institutions

Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Reha Rheinfelden Switzerland (CH) Shaare Zedek Medical Center / מרכז רפואי שערי צדק‎‎, Israel (IL) az groeninge Belgium (BE) Universitätsklinikum Mannheim Germany (DE) Lausanne University Hospital / Centre hospitalier universitaire vaudois (CHUV) Switzerland (CH) Helsinki University Central Hospital (HUCH) / Helsingin seudun yliopistollinen keskussairaala (HYKS) Finland (FI) Glan Clwyd Hospital / Ysbyty Glan Clwyd United Kingdom (GB) University Hospital of North Durham / Dryburn Hospital United Kingdom (GB) Morriston Hospital United Kingdom (GB) Universitätsklinikum Heidelberg Germany (DE) University Hospital Ghent Belgium (BE) Central Lisbon University Hospital Centre / Centro Hospitalar Universitário de Lisboa Central (CHULC) Portugal (PT) Universitätsklinikum Freiburg Germany (DE) Universität Bern Switzerland (CH) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Università degli studi "La Sapienza" Italy (IT) Università degli Studi di Perugia Italy (IT) Universitätsspital Basel Switzerland (CH) Inselspital, Universitätsspital Bern Switzerland (CH) General University Hospital of Larissa Greece (GR) Medizinische Universität Graz Austria (AT) Mater Misericordiae University Hospital (MMUH) / Ospidéal an Mater Misercordiae Ireland (IE) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven Belgium (BE) Sree Chitra Thirunal Institute for Medical Sciences and Technology (SCTIMST) India (IN) Pavol Jozef Šafárik University in Kosice / Univerzita Pavla Jozefa Šafárika v Košiciach Slovakia (SK) National Cerebral and Cardiovascular Center Japan (JP) Kantonsspital St.Gallen Switzerland (CH) Jichi Medical University / 自治医科大学 Japan (JP) University of Oslo Norway (NO) University College London (UCL) United Kingdom (GB) Sahlgrenska University Hospital / Sahlgrenska Universitetssjukhuset Sweden (SE) St George’s University Hospitals NHS Foundation Trust United Kingdom (GB) Kansai Medical University Japan (JP) Kepler Universitätsklinikum (KUK) Austria (AT) Hertie-Institut für klinische Hirnforschung Germany (DE) University of Glasgow United Kingdom (GB)

How to cite

APA:

Fischer, U., Koga, M., Strbian, D., Branca, M., Abend, S., Trelle, S.,... Dawson, J. (2023). Early versus Later Anticoagulation for Stroke with Atrial Fibrillation. New England Journal of Medicine, 388(26), 2411-2421. https://dx.doi.org/10.1056/NEJMoa2303048

MLA:

Fischer, Urs, et al. "Early versus Later Anticoagulation for Stroke with Atrial Fibrillation." New England Journal of Medicine 388.26 (2023): 2411-2421.

BibTeX: Download