Prior Reperfusion Strategy Does Not Modify Outcome in Early Versus Late Start of Anticoagulants in Patients With Ischemic Stroke: Prespecified Subanalysis of the Randomized Controlled ELAN Trial

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.