Anticoagulation treatment after an ischemic stroke should be started earlier

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An international clinical trial, which involved experts from Glasgow, has concluded that anticoagulation treatment could be safely started earlier than current recommended guidelines in patients following ischemic stroke with atrial fibrillation.

The study - published in the New England Journal of Medicine and led by the led by the Stroke Center, Inselspital, University Hospital Bern, and the University of Bern - found the chances of suffering a recurrent event with earlier treatment were likely to be lower compared to a later start, without an increase in risk of complications.

The ELAN (Early versus Late initiation of direct oral Anticoagulants in post-ischemic stroke patients with atrial fibrillatioN) trial was co-designed and co-led by researchers at the University of Glasgow. The study included 2013 participants - including more than 400 from the UK - with an acute ischemic stroke and atrial fibrillation recruited from 103 different stroke units in 15 different countries in Europe, the Middle East and Asia between 2017 and 2022.

Around 80% of all strokes are caused by occlusion of an artery in the brain. Up to 20% of these are caused by blood clots, which form in the heart in people with atrial fibrillation. Atrial fibrillation is an irregular heart rhythm that affects as many as 5% of people over the age of 65 years.

Blood thinners called direct oral anticoagulants (DOACs) are used to prevent blood clots in people with atrial fibrillation but it is unclear how early after stroke they should be started. There is a potential increased risk of bleeding into the stroke which may be highest in the first few days. However, the potential benefit of these drugs may also be highest in these first few days. In the presence of this uncertainty, international guidelines recommend a delay before starting DOACs.

Based on the size and location of the infarct on imaging (i.e. a minor, moderate or major stroke), participants in the study were randomly assigned to an early treatment start or a later, guideline recommended, treatment start. An early start was defined as within 48 hours of a minor/moderate stroke or day 6-7 following a major stroke. A late start was defined as day 3-4 following a minor stroke, day 6-7 following a moderate stroke, or day 12-14 following a major stroke. The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, extracranial bleeding, systemic embolism, or vascular death within 30 days after randomisation.

Professor Jesse Dawson, Professor of Stroke Research at the University of Glasgow’s School of Cardiovascular and Metabolic Health, said: "The study suggests that the incidence of symptomatic intracerebral hemorrhage is low with early anticoagulation, if imaging based classification is used. Moreover, we now know that waiting several days to start anticoagulation in people with ischemic stroke and AF is not safer and is likely to be associated with higher stroke risk."

Study lead Professor Urs Fischer, from the University Hospitals of Bern and Basel, said: "Our study finally brings scientific evidence for a common dilemma in early secondary prevention after an ischemic stroke. In view of our results, early treatment initiation is reasonable if indicated or if desired for logistic or other reasons. It is probably better and is unlikely to cause harm."

As a next step, the researchers plan to explore whether the risk and benefit is similar in different subgroups of the ELAN trial population, especially in people more severely affected.

Richard Francis, Head of Research at the Stroke Association said: "Around 1.2 million people in the UK have atrial fibrillation (AF), a type of irregular heartbeat. Having AF means that blood clots are more likely to form in your heart, increasing your risk of stroke.

"We’re delighted to have helped fund this important clinical trial which shows that earlier treatment with DOACs could reduce the chances of suffering another stroke compared to a later start, without an increase in risk of complications.

"We know that nine out of ten stroke survivors are afraid of having another stroke; so these findings have the potential to ease this anxiety. However, before the ELAN findings are adopted into clinical practice, it is important that we understand whether the balance of benefit and risk with early blood thinners is different depending on factors like ethnicity, sex or severity of stroke. We look forward to follow-up research that can help answer this question."

The study, ’Early versus Late Anticoagulation for Stroke with Atrial Fibrillation,’ is published in the NEJM.