ABSTRACT NUMBER: ESOC2026A679 CONTINUATION VERSUS SWITCHING DIRECT ORAL ANTICOAGULANT AFTER BREAKTHROUGH STROKE: A NON-INFERIORITY TARGET TRIAL ANALYSIS FROM THE ASPERA-R STUDY

Abstract Background and aims Management strategies after ischemic stroke occurring despite direct oral anticoagulant (DOAC) therapy for atrial fibrillation vary widely, and switching anticoagulation is common despite limited supporting evidence. We compared the effectiveness and safety of continuing the same DOAC versus switching to another oral anticoagulant after a breakthrough stroke using a prespecified non-inferiority framework. Methods We conducted an emulated target trial within a non-inferiority framework to compare continuation versus switching anticoagulation strategies using data from the multicentre, retrospective ASPERA registry. Adult patients with atrial fibrillation who experienced a breakthrough ischemic stroke while receiving uninterrupted DOAC therapy were included. The primary outcome was 90-day net clinical benefit, defined as the composite of recurrent ischemic stroke and moderate-to-severe bleeding; secondary outcomes included recurrent ischemic events, symptomatic intracranial haemorrhage, all-cause and vascular mortality. Baseline confounding was addressed using inverse probability of treatment weighting (IPTW). Results Overall, 1006 patients were included (median age 80.4 years [IQR 73.4–85.4]; 50% women). DOAC therapy was continued in 463 patients and switched to another DOAC or vitamin K antagonist in 543. After IPTW adjustment, 90-day net clinical benefit was similar between strategies (5.1% vs 4.9%), with a risk difference of −0.3% (90% CI −2.7% to 2.1%), meeting the non-inferiority criterion. Secondary outcomes were comparable, whereas non-inferiority was not demonstrated for all-cause or vascular mortality. Conclusions In this multinational emulated target trial, continuation of the same DOAC after breakthrough stroke was associated with clinical outcomes comparable to switching anticoagulant therapy, with absolute differences remaining within clinically acceptable margins for most outcomes. Conflict of interest nothing to disclose