OPTIMAS Trial
Research type
Research Study
Full title
OPtimal TIMing of Anticoagulation after acute ischaemic Stroke: a randomised controlled trial (OPTIMAS Trial)
IRAS ID
249552
Contact name
David Werring
Contact email
Sponsor organisation
Comprehensive Clinical Trials Unit, University College London
Eudract number
2018-003859-38
ISRCTN Number
ISRCTN17896007
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
UKCRN, 40836
Duration of Study in the UK
3 years, 11 months, 31 days
Research summary
Atrial fibrillation (AF) is a type of irregular heartbeat that can cause blood clots to form in the heart. The movement of these clots can block blood vessels in the brain, causing a type of stroke known as a cardioembolic ischaemic stroke. Direct oral anticoagulants (DOACs) are medicines prescribed to prevent further strokes in people with AF who have had a stroke, and are usually started 7-14 days after stroke as standard care. However, it is unclear if starting DOAC treatment earlier than standard care could benefit patients; early treatment (up to 4 days after stroke) may lower the risk of further stroke, but may increase the risk of major bleeding, especially in the brain.
This trial aims to compare the effectiveness of early DOAC treatment to prevent recurrent stroke and systemic embolism (i.e. a blood clot in an artery) in patients with acute ischaemic stroke and AF with that of standard timing of DOAC treatment. The four DOACs that are usually prescribed to prevent recurrent stroke are dabigatran, apixaban, rivaroxaban, edoxaban, and they will be used according to their drug licenses in this trial. The choice of DOAC will be decided by the treating doctor, but the timing of treatment will be allocated to either early or standard. It is expected that 3500 adult patients (≥18 years) admitted to +100 participating acute stroke units with acute ischaemic stroke and AF will be screened for eligibility, and consented (by patient or legal representative if the patient is too unwell to make their own decisions). They will then be entered into the trial receive early or standard DOAC treatment. Patients who cannot have anticoagulant treatment because of specific conditions such as an increased tendency to bleed or poor liver function will be excluded.Participants will be followed up at 90 days post-study entry to collect information on how well they have taken DOAC treatment (known as adherence), side effects, and whether they have had specific clinical events such as stroke, bleeding, and systemic embolism. This information will allow the researchers to calculate the rate of newly-occurring stroke, bleeding in the brain (symptomatic intracranial haemorrhage), and systemic embolism in the 90 day treatment period for each of the two groups (early and standard) so they can be compared. The impact of early versus standard treatment on participants’ quality of life and cognition will also be investigated by using specific assessments.
Lay summary of study results: The OPTIMAS (Optimal timing of anticoagulation after acute ischaemic stroke with atrial fibrillation) trial investigated the best time to start blood-thinning medicines, known as direct oral anticoagulants (DOACs), for people who have had a stroke due to a blocked artery (ischaemic stroke) and have an irregular heartbeat (atrial fibrillation). Stroke doctors have long debated whether starting these medicines early increases the risk of bleeding in the brain or whether delaying treatment increases the chance of another stroke due to blood clots forming in the heart. Current guidelines suggest waiting before starting treatment, but there has been little high-quality evidence to guide this decision.OPTIMAS was conducted in 100 hospitals across the UK between July 2019 and January 2024. The study included adults who had recently suffered a stroke and had been diagnosed with atrial fibrillation. Participants were randomly divided into two groups: one group started DOAC treatment within four days of their stroke (early initiation), while the other group started between seven and 14 days later (delayed initiation). The trial monitored participants for 90 days to assess their health outcomes, including the risk of another stroke due to a blocked artery or bleeding in or around the brain.
In total, 3,621 patients took part in the study (1,814 in the early treatment group and 1,807 in the delayed treatment group). The main finding was that starting blood-thinning medicine earlier was just as safe and effective as starting it later. There was no significant difference between the two groups in the risk of major brain bleeding or recurrent stroke. This challenges the traditional approach of delaying treatment and suggests that patients can safely receive anticoagulation sooner after a stroke.
The trial followed strict protocols to ensure accuracy and fairness. It used a "randomised open-label" design, meaning that both participants and their doctors knew which group they were in, but an independent committee that reviewed the outcome events was blinded to the treatment groups. Before starting the treatment, participants underwent brain imaging to rule out bleeding or other conditions that could make anticoagulation unsafe. The study also excluded individuals with severe bleeding risks or kidney problems to ensure safety.
OPTIMAS also showed that stroke severity, previous anticoagulant use, or other treatments like clot-busting drugs did not change the main findings, indicating that early anticoagulation is safe in these patient groups in whom doctors have previously been concerned about bleeding risks.
While the results support earlier treatment, the study had some limitations. For instance, it did not include patients who would have started DOAC treatment between four and seven days after their stroke, so it remains unclear how this timing compares. Additionally, there were fewer participants with severe strokes, meaning more research is needed to confirm the safety of early treatment in these cases.In conclusion, the OPTIMAS trial provides strong evidence that starting DOAC treatment soon after an ischaemic stroke in patients with atrial fibrillation is as safe and effective as later treatment. These findings could lead to changes in clinical practice, allowing patients to receive earlier treatment and better protection against further strokes. However, further research is needed to refine the best timing, particularly for those with very severe strokes. A large, combined analysis of all available randomised trial evidence, called CATALYST, will help with these and other outstanding questions.
REC name
South Central - Oxford B Research Ethics Committee
REC reference
19/SC/0021
Date of REC Opinion
14 Mar 2019
REC opinion
Further Information Favourable Opinion