Continuation versus switching direct oral anticoagulant after breakthrough stroke
File(s)
Accepted version
Author(s)
D'Anna, Lucio
Type
Journal Article
Abstract
Importance. Management after an ischemic stroke occurring despite direct oral anticoagulant (DOAC) therapy for atrial fibrillation (AF) varies widely. Switching anticoagulation is common in clinical practice, although evidence supporting this strategy is limited.
Objective. To evaluate whether continuation of the same DOAC was non-inferior to switching oral anticoagulant therapy with respect to 90-day clinical outcomes.
Design, setting and participants. Multicentre registry-based emulated target trial including consecutive adult patients with AF who experienced a breakthrough ischemic stroke while receiving uninterrupted DOAC therapy and resumed anticoagulation thereafter. Patients were enrolled between 2020 and 2025 across 35 stroke centres in 9 countries in Europe and North Africa, with standardized 90-day follow-up. A non-inferiority comparison of switching versus continuation strategies was performed. Baseline confounding was addressed using inverse probability of treatment weighting (IPTW). The primary non-inferiority margin was +3.0% absolute risk difference in 90-day net clinical benefit.
Exposure. Switching to a different DOAC or vitamin K antagonist was the intervention group and continuation of the pre-stroke DOAC was the comparator group. Main Outcomes and Measures. The primary outcome was 90-day net clinical benefit, defined as recurrent ischemic stroke and moderate-to-severe bleeding. Secondary outcomes included recurrent ischemic events, symptomatic intracranial haemorrhage, moderate-to-severe extracranial bleeding, all-cause mortality, and vascular death.
Results. Among 1006 patients (median age 80.4 years [IQR, 73.4–85.4]; 503 women [50.0%]), 463 (46.0%) continued the same DOAC and 543 (54.0%) switched therapy. After IPTW adjustment, the 90-day net clinical benefit was 4.9% with switching and 5.1% with continuation, corresponding to a risk difference of −0.3% (90% CI, −2.7% to 2.1%), meeting the prespecified noninferiority criterion. For recurrent ischemic events and bleeding outcomes the absolute differences were within the predefined non-inferiority margins. Noninferiority was
not demonstrated for all-cause or vascular mortality.
Conclusions and Relevance. In patients with breakthrough ischemic stroke during DOAC therapy, switching anticoagulation was not associated with clinically meaningful short-term benefit compared with continuation. According to our findings switching did not provide additional benefit compared to continuing the same DOAC. Randomized controlled trials are needed to identify strategies to improve secondary prevention after a breakthrough ischemic stroke.
Objective. To evaluate whether continuation of the same DOAC was non-inferior to switching oral anticoagulant therapy with respect to 90-day clinical outcomes.
Design, setting and participants. Multicentre registry-based emulated target trial including consecutive adult patients with AF who experienced a breakthrough ischemic stroke while receiving uninterrupted DOAC therapy and resumed anticoagulation thereafter. Patients were enrolled between 2020 and 2025 across 35 stroke centres in 9 countries in Europe and North Africa, with standardized 90-day follow-up. A non-inferiority comparison of switching versus continuation strategies was performed. Baseline confounding was addressed using inverse probability of treatment weighting (IPTW). The primary non-inferiority margin was +3.0% absolute risk difference in 90-day net clinical benefit.
Exposure. Switching to a different DOAC or vitamin K antagonist was the intervention group and continuation of the pre-stroke DOAC was the comparator group. Main Outcomes and Measures. The primary outcome was 90-day net clinical benefit, defined as recurrent ischemic stroke and moderate-to-severe bleeding. Secondary outcomes included recurrent ischemic events, symptomatic intracranial haemorrhage, moderate-to-severe extracranial bleeding, all-cause mortality, and vascular death.
Results. Among 1006 patients (median age 80.4 years [IQR, 73.4–85.4]; 503 women [50.0%]), 463 (46.0%) continued the same DOAC and 543 (54.0%) switched therapy. After IPTW adjustment, the 90-day net clinical benefit was 4.9% with switching and 5.1% with continuation, corresponding to a risk difference of −0.3% (90% CI, −2.7% to 2.1%), meeting the prespecified noninferiority criterion. For recurrent ischemic events and bleeding outcomes the absolute differences were within the predefined non-inferiority margins. Noninferiority was
not demonstrated for all-cause or vascular mortality.
Conclusions and Relevance. In patients with breakthrough ischemic stroke during DOAC therapy, switching anticoagulation was not associated with clinically meaningful short-term benefit compared with continuation. According to our findings switching did not provide additional benefit compared to continuing the same DOAC. Randomized controlled trials are needed to identify strategies to improve secondary prevention after a breakthrough ischemic stroke.
Date Acceptance
2026-03-05
Citation
JAMA Network Open
ISSN
2574-3805
Publisher
JAMA Network
Journal / Book Title
JAMA Network Open
Copyright Statement
Copyright This paper is embargoed until publication. Once published the Version of Record (VoR) will be available on immediate open access.
License URL
Publication Status
Accepted