medwireNews: Initiating direct oral anticoagulants (DOACs) within 4 days of an acute ischemic stroke in patients with atrial fibrillation is as effective and tolerable as delayed initiation shows the OPTIMAS study published in The Lancet.
The findings “do not support the common and guideline-recommended practice of delaying treatment due to concerns about intracranial hemorrhage, irrespective of baseline stroke severity,” say David Werring (University College London, UK) and colleagues.
They compared the outcomes with early (up to 4 days) versus delayed (7–14 days) initiation after stroke symptom onset in a phase 4 study conducted at 100 UK hospitals between 2019 and 2024.
Eligible patients had atrial fibrillation and a clinical diagnosis of acute ischemic stroke of any infarct size or severity and their physicians were “uncertain of the optimal timing for DOAC initiation,” Werring et al explain.
Of the 3621 adult patients in the intention-to-treat population (55% men; mean age 78.5 years), 1814 were randomly assigned to receive early DOAC initiation (a mean of 3.1 days after stroke onset) and 1807 instead received late DOAC initiation (a mean of 8.3 days after stroke onset). Overall, the participants had a median National Institutes of Health Stroke Scale (NIHSS) score of 5 points on study admission.
Werring and colleagues report that the two groups had an equivalent 3.3% incidence of the composite outcome by the 90-day follow-up, namely recurrent ischemic stroke, symptomatic intracranial hemorrhage, unclassifiable stroke, or systemic embolism, which they say was within the study’s noninferiority margin of 2 percentage points.
Overall, 8.8% of the patients had died and 1.9% had withdrawn from their trial treatment by the end of follow-up.
Of note, there were 23 incidents of symptomatic intracranial hemorrhage within 90 days, occurring at similar rates of 0.6% and 0.7% in the early versus late DOAC initiation groups, respectively, which the researchers say is “very low.” They add that this suggests “starting a DOAC early after acute ischaemic stroke associated with atrial fibrillation in patients without known contraindications is safe (with regard to symptomatic intracranial haemorrhage).”
The investigators say that there were “no significant differences” between the early and delayed treatment groups when assessing other individual outcomes at 90 days. These included recurrent ischemic stroke (2.4 vs 2.3%), systemic embolism (0.1 vs 0.2%), unclassifiable stroke (0.2 vs 0.1%), and all-cause mortality (8.8 vs 8.9%), as well as a composite of the primary outcome or mortality (10.8 vs 10.5%), major extracranial bleeding (0.4 vs 0.7%), non-major extracranial bleeding (2.5 vs 2.0%), or all major bleeding (1.0 vs 1.4%).
The findings were unaffected by stroke severity, when the patients were stratified according to the NIHSS scores of 0–10 points and greater than 10 points.
Likewise, the results were consistent irrespective of age, sex, and receipt of reperfusion or anticoagulation therapies prior to stroke. In all, 32.2% of patients were taking a DOAC and 3.1% were taking a vitamin K antagonist at the time of stroke onset. This finding therefore provides “important reassurance about the safety of restarting a DOAC within the first 4 days in this patient group,” say the authors.
Werring and team comment on the benefit of the size of their study population and its broad eligibility criteria “intended to give a representative study sample and provide results that are readily applicable to clinical practice.”
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