Early versus Later Anticoagulation for Stroke with Atrial Fibrillation.
Humans
Anticoagulants
/ administration & dosage
Atrial Fibrillation
/ complications
Embolism
/ etiology
Hemorrhage
/ chemically induced
Intracranial Hemorrhages
/ chemically induced
Ischemic Stroke
/ etiology
Stroke
/ etiology
Treatment Outcome
Time Factors
Factor Xa Inhibitors
/ administration & dosage
Recurrence
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
29 Jun 2023
29 Jun 2023
Historique:
medline:
30
6
2023
pubmed:
24
5
2023
entrez:
24
5
2023
Statut:
ppublish
Résumé
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. 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. 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. 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.).
Sections du résumé
BACKGROUND
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
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
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
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.).
Identifiants
pubmed: 37222476
doi: 10.1056/NEJMoa2303048
doi:
Substances chimiques
Anticoagulants
0
Factor Xa Inhibitors
0
Banques de données
ClinicalTrials.gov
['NCT03148457']
Types de publication
Comparative Study
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
2411-2421Subventions
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
ID : 32003B_197009; 32003B_169975
Organisme : Stroke Association
ID : 2017/02
Investigateurs
Azmil Abdul-Rahim
(A)
Youssif Abousleiman
(Y)
Anastasia Adamou
(A)
Adedolapo Kamaldeen Adeyemi
(AK)
Sylvan J Albert
(SJ)
Lars Alteheld
(L)
Hisanao Akiyama
(H)
Marianne Altmann
(M)
Alexander Andrea Tarnutzer
(AA)
Tal Anjum
(T)
Arunkumar Annamalai
(A)
Ijaz Anwar
(I)
Markus Arnold
(M)
Mark Barber
(M)
Anne Berberich
(A)
Ingrid Olave Bersas
(IO)
Rohit Bhatia
(R)
Giovanni Bianco
(G)
Manuel Bolognese
(M)
Christophe Bonvin
(C)
Victoria Borisova
(V)
David Bradley
(D)
Christina Caporale
(C)
Tim Cassidy
(T)
Carlo W Cereda
(CW)
Daniel Charissé
(D)
Carla Ciobanu
(C)
Brian Clarke
(B)
Sandra Clarke
(S)
Ronan Collins
(R)
Telma Costa
(T)
Veerle De Herdt
(V)
Gian Marco De Marchis
(GM)
Nicole Del Gaudio
(N)
François Delvoye
(F)
Annemie Devroye
(A)
Aneesh Dhasan
(A)
Lynn Dixon
(L)
Jeyaraj Durai Pandian
(JD)
Harvey Dymond
(H)
Roni Eichel
(R)
Sapna Erat Sreedharan
(SE)
Derek Esson
(D)
Anne Falcou
(A)
Simon Fandler-Höfler
(S)
Loraine Fisch
(L)
Anna Fischer
(A)
Shigeru Fujimoto
(S)
Sofia Galego
(S)
Melissa Garcia-Pons
(M)
Lukuman Gbadamosh
(L)
Luana Gentile
(L)
Maria Giulia Mosconi
(MG)
Christoph Globas
(C)
Catia Gonçalves Martins
(C)
Stefan Greisenegger
(S)
Matthias Greulich
(M)
Ben Grimshaw
(B)
Vipul Gupta
(V)
German Guzman-Gutierrez
(G)
Michael Haley
(M)
Joseph Harbison
(J)
Liam Healy
(L)
Asaf Honig
(A)
Arne Hostens
(A)
Vikram Huded
(V)
Andrea M Humm
(AM)
Samer Al Hussayni Husseini
(S)
Yasuyuki Iguchi
(Y)
Hege Ihle-Hansen
(H)
Manabu Inoue
(M)
Thomas Iype
(T)
Zuzana Jankovicova
(Z)
Mary Joan MacLeod
(MJ)
Georg Kägi
(G)
Bernd Kallmünzer
(B)
Efstathia Karagkiozi
(E)
Mira Katan
(M)
Katarina Klimcikova
(K)
Risa Kato
(R)
Lukas Kellermair
(L)
Lars Kellert
(L)
Dheeraj Khurana
(D)
Himanshu Koundal
(H)
Christos Krogias
(C)
Vishav Kumar
(V)
Takenobu Kunieda
(T)
Marie Lang
(M)
Ilaria Leone De Magistris
(IL)
Ronen R Leker
(RR)
Arthur Liesz
(A)
Caroline Loos
(C)
Kosmas Macha
(K)
Marta Magriço
(M)
Niranjan Mahajan
(N)
Miroslav Mako
(M)
Evelyn Marcelis
(E)
Rados Marian
(R)
Michael Marnane
(M)
Nicolas Martinez-Majander
(N)
João Pedro Marto
(JP)
Soichiro Matsubara
(S)
Joshua Mbroh
(J)
Christine McAlpine
(C)
John J McCabe
(JJ)
Friedrich Medlin
(F)
Diana Melancia
(D)
Brian Menezes
(B)
Dominik Michalski
(D)
Ole Morten Rønning
(OM)
Riona Mulcahy
(R)
Martin Müller
(M)
Anna Müller
(A)
Yngve Müller Seljeseth
(YM)
Ioan-Paul Muresan
(IP)
Darius G Nabavi
(DG)
Priya Nair
(P)
Makoto Nakajima
(M)
Aumugam Nallasivan
(A)
Vivek Nambiar
(V)
Julien Niederhauser
(J)
Imelda Noone
(I)
Stefan Oberndorfer
(S)
Jens Offermann
(J)
Elisabeth Olbert
(E)
Oezguer A Onur
(OA)
David Orion
(D)
Sarah Ostanek
(S)
Asterios Paliantonis
(A)
Vijaya Pamidimukkala
(V)
Tatjana Pap
(T)
Rajsrinivas Parthasarathy
(R)
Johann Pelz
(J)
Zoltan Pencz
(Z)
André Peeters
(A)
Nils Peters
(N)
Waltraud Pfeilschifter
(W)
Alexander Pichler
(A)
Teresa Pinho E Melo
(T)
Mette Pøhner Skahjem
(M)
Naren Polavarapu
(N)
Svetlana Politz
(S)
Alexandros Polymeris
(A)
George Pope
(G)
Marios Psychogios
(M)
Karthika Rani
(K)
Sucharita Ray
(S)
Susanne Renaud
(S)
Daniel Richter
(D)
Susanne Riebau
(S)
Peter Ringleb
(P)
Biljana Rodic
(B)
Georg Royl
(G)
Matthieu Pierre Rutgers
(MP)
Dan Ryan
(D)
João Sargento-Freitas
(J)
Takeo Sato
(T)
Anna Maija Saukkonen
(AM)
Maximilian Schell
(M)
Ludwig Schelosky
(L)
Eckhard Schlemm
(E)
Daniel Schrammel
(D)
Adrian Scutelnic
(A)
Gerli Sibolt
(G)
Norbert Silimon
(N)
Jussi Sipilä
(J)
Gaia Sirimarco
(G)
Amina Sellimi
(A)
Kerry Smith
(K)
Gemma Marie Smith
(GM)
Klaudia Soltesova
(K)
João André Sousa
(JA)
Torstein Spetalen
(T)
Dimitre Staykov
(D)
Henning R Stetefeld
(HR)
Wendy Stoop
(W)
Sharon Storton
(S)
Davide Strambo
(D)
Kristina Szabo
(K)
Fukano Takayuki
(F)
Ryota Tanaka
(R)
Danilo Toni
(D)
Alexander Vanhoorne
(A)
Isabelle Vanpanteghem
(I)
Adhiyaman Vedamurthy
(A)
Arvind Vijaysharan Sharma
(AV)
Tim J Von Oertzen
(TJ)
Milan Vosko
(M)
Jan Vynckier
(J)
Judith Wagner
(J)
Clare Whyte
(C)
Ami Wilkinson
(A)
Alastair Wilson
(A)
Fiona Wright
(F)
Sohei Yoshimura
(S)
Laetitia Yperzeele
(L)
Andrea Zini
(A)
Informations de copyright
Copyright © 2023 Massachusetts Medical Society.