TY - JOUR
T1 - Prior Reperfusion Strategy Does Not Modify Outcome in Early Versus Late Start of Anticoagulants in Patients With Ischemic Stroke
T2 - Prespecified Subanalysis of the Randomized Controlled ELAN Trial
AU - Wouters, Anke
AU - Demeestere, Jelle
AU - Rossel, Jean-Benoît
AU - Devroye, Annemie
AU - Desfontaines, Philippe
AU - Vanacker, Peter
AU - Hemelsoet, Dimitri
AU - Yperzeele, Laetitia
AU - Rutgers, Matthieu Pierre
AU - Peeters, André
AU - Vynckier, Jan
AU - Yoshimoto, Takeshi
AU - Tanaka, Kanta
AU - Vehoff, Jochen
AU - Matsuzono, Kosuke
AU - Kulyk, Caterina
AU - Sibolt, Gerli
AU - Slade, Peter
AU - Salerno, Alexander
AU - Kunieda, Takenobu
AU - Hakim, Arsany
AU - Rohner, Roman
AU - Abend, Stefanie
AU - Goeldlin, Martina
AU - Dawson, Jesse
AU - Fischer, Urs
AU - Lemmens, Robin
AU - ELAN Investigators
PY - 2025/5/22
Y1 - 2025/5/22
N2 - BACKGROUND: Early initiation of direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation and acute ischemic stroke is beneficial and safe. Whether prior acute reperfusion therapy modifies the treatment effect of early versus late DOAC initiation is unknown.METHODS: For this post hoc analysis of the multicenter, randomized controlled ELAN trial (Early Versus Late Initiation of Direct Oral Anticoagulants in Post-Ischaemic Stroke Patients With Atrial Fibrillation), all participants with data concerning reperfusion treatment were included. The primary outcome was the composite outcome of recurrent ischemic stroke, symptomatic intracranial hemorrhage, major extracranial bleeding, systemic embolism, or vascular death within 30 days. Patients were divided into 4 groups based on prior reperfusion therapy: no treatment, intravenous thrombolysis (IVT), endovascular treatment (EVT), or IVT combined with EVT. We performed logistic regression adjusted for age, hypertension, infarct location/size, pre-modified Rankin Scale, NIHSS, and hemorrhagic transformation, including the interaction term between treatment groups (early versus late DOAC) and reperfusion strategy.RESULTS: We included 1973 of 2013 (98%) patients of the ELAN trial population, with a median age of 77 (71-84) years and of whom 899 (46%) were female. Of them, 1015 (51%) underwent no prior reperfusion treatment, 519 (26%) IVT, 190 (10%) EVT, and 249 (13%) IVT+EVT. We did not identify an interaction for any of the outcome events between prior reperfusion therapy and timing of DOAC initiation. Rates were numerically lower in the early DOAC-initiated group for the following: no reperfusion therapy, 17 (3.3%) versus 24 (4.8%; adjusted odds ratio, 0.69 [95% CI, 0.36-1.28]); EVT, 1 (1.2%) versus 7 (6.4%; adjusted odds ratio, 0.25 [95% CI, 0.03-1.21]); and EVT+IVT, 3 (2.4%) versus 4 (3.3%; adjusted odds ratio, 0.76 [95% CI, 0.17-3.23]). In patients who had received IVT, the rates were 3% (n=8) in the early group versus 2% (n=5) in the late group (adjusted odds ratio, 1.52 [95% CI, 0.52-4.84]).CONCLUSIONS: Prior reperfusion therapy does not modify the effect of early versus late DOAC initiation on clinical outcomes in patients with atrial fibrillation and acute ischemic stroke.REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03148457.
AB - BACKGROUND: Early initiation of direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation and acute ischemic stroke is beneficial and safe. Whether prior acute reperfusion therapy modifies the treatment effect of early versus late DOAC initiation is unknown.METHODS: For this post hoc analysis of the multicenter, randomized controlled ELAN trial (Early Versus Late Initiation of Direct Oral Anticoagulants in Post-Ischaemic Stroke Patients With Atrial Fibrillation), all participants with data concerning reperfusion treatment were included. The primary outcome was the composite outcome of recurrent ischemic stroke, symptomatic intracranial hemorrhage, major extracranial bleeding, systemic embolism, or vascular death within 30 days. Patients were divided into 4 groups based on prior reperfusion therapy: no treatment, intravenous thrombolysis (IVT), endovascular treatment (EVT), or IVT combined with EVT. We performed logistic regression adjusted for age, hypertension, infarct location/size, pre-modified Rankin Scale, NIHSS, and hemorrhagic transformation, including the interaction term between treatment groups (early versus late DOAC) and reperfusion strategy.RESULTS: We included 1973 of 2013 (98%) patients of the ELAN trial population, with a median age of 77 (71-84) years and of whom 899 (46%) were female. Of them, 1015 (51%) underwent no prior reperfusion treatment, 519 (26%) IVT, 190 (10%) EVT, and 249 (13%) IVT+EVT. We did not identify an interaction for any of the outcome events between prior reperfusion therapy and timing of DOAC initiation. Rates were numerically lower in the early DOAC-initiated group for the following: no reperfusion therapy, 17 (3.3%) versus 24 (4.8%; adjusted odds ratio, 0.69 [95% CI, 0.36-1.28]); EVT, 1 (1.2%) versus 7 (6.4%; adjusted odds ratio, 0.25 [95% CI, 0.03-1.21]); and EVT+IVT, 3 (2.4%) versus 4 (3.3%; adjusted odds ratio, 0.76 [95% CI, 0.17-3.23]). In patients who had received IVT, the rates were 3% (n=8) in the early group versus 2% (n=5) in the late group (adjusted odds ratio, 1.52 [95% CI, 0.52-4.84]).CONCLUSIONS: Prior reperfusion therapy does not modify the effect of early versus late DOAC initiation on clinical outcomes in patients with atrial fibrillation and acute ischemic stroke.REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03148457.
KW - Humans
KW - Female
KW - Male
KW - Aged
KW - Ischemic Stroke/drug therapy
KW - Anticoagulants/therapeutic use
KW - Treatment Outcome
KW - Aged, 80 and over
KW - Atrial Fibrillation/drug therapy
KW - Reperfusion/methods
KW - Thrombolytic Therapy/methods
KW - Endovascular Procedures
KW - Time Factors
KW - Brain Ischemia/drug therapy
KW - Middle Aged
UR - https://www.scopus.com/pages/publications/105006589934
U2 - 10.1161/STROKEAHA.125.050646
DO - 10.1161/STROKEAHA.125.050646
M3 - Article
C2 - 40402090
SN - 1524-4628
VL - 56
SP - 2000
EP - 2008
JO - Stroke
JF - Stroke
IS - 8
ER -
