OPTIMAS Trial: Optimal Timing of DOACs After AF-Related Ischemic Stroke
In patients with AF-related acute ischemic stroke, is early DOAC initiation within 4 days non-inferior to delayed initiation (7-14 days) for the composite of recurrent stroke, symptomatic ICH, or systemic embolism at 90 days?
Werring et al. (Lancet 2024) · 3621 patients
Population
Included
- Adults with acute ischemic stroke and confirmed atrial fibrillation
- Clinical indication for long-term anticoagulation
- Randomization at 100 UK stroke centers
Eligible patients
- Adults aged 18 years or older
- Atrial fibrillation confirmed by an electrocardiogram or medical records
- Clinical diagnosis of acute ischemic stroke with symptoms lasting at least 24 hours, or at least one form of brain imaging (CT or MRI) to exclude intracranial hemorrhage and non-stroke diagnoses
- Eligible for anticoagulation with a DOAC, with the responsible treating physician uncertain about the optimal timing to start anticoagulation
Excluded
- Mechanical heart valve
- Active major bleeding or very high bleeding risk
- Severe renal impairment precluding DOAC use
- Inability to consent or take oral medication
Bleeding and coagulation
- Coagulopathy, or evidence of recent or current anticoagulation with a vitamin K antagonist leading to an international normalized ratio of 1.7 or higher at randomization
- Clinically significant thrombocytopenia (platelet count below 75 x 10^9 per litre)
- Coagulopathy or bleeding tendency judged to contraindicate anticoagulation by the treating clinician
Imaging and infarct features
- Severe hemorrhagic transformation of the acute infarct (parenchymal hematoma type 2 by the Heidelberg criteria), or an acute intracranial hemorrhage unrelated to the acute infarct
- Brain imaging evidence of non-stroke pathology judged likely to explain the clinical presentation (for example mass lesion or encephalitis)
Drug, organ, and other contraindications
- Contraindication to DOAC use (severe renal impairment with creatinine clearance below 15 mL/min, cirrhosis with Child-Pugh class B or C, alanine aminotransferase more than 2 times the upper limit of normal, or concurrent medication with a notable DOAC interaction such as strong CYP3A4 inducers)
- Known allergy or intolerance to Factor Xa and direct thrombin inhibitors
- Definite indication for a vitamin K antagonist (for example a mechanical heart valve)
- Pregnant or breastfeeding
- Could not be followed up for 90 days after trial entry, or did not consent to study procedures
Source: Werring DJ et al., Lancet 2024· Retrieved 2026-06-09
Primary Outcome — Composite at 90 Days (Non-inferiority)
3621 patients at 100 UK hospitals; early DOAC within 4 days vs delayed 7-14 days
Non-inferiority design
This trial tested whether early DOAC is no worse than delayed initiation, not whether it is better. Event rates were identical (3.3% vs 3.3%). Non-inferiority met (P=0.0003); superiority was not demonstrated.
Negligible absolute difference
Composite: Recurrent Stroke, sICH, or Systemic Embolism at 90 Days
Study Arms
- Agent
- Direct oral anticoagulant (apixaban, dabigatran, edoxaban, or rivaroxaban)
- Dose
- Licensed stroke-prevention dose for the chosen DOAC; dose and route per the relevant summary of product characteristics, at physician discretion
- Route
- Oral
- Frequency
- Per product labeling for the chosen DOAC
- Duration
- Initiated within 4 days (on or before day 4) of stroke onset; long-term anticoagulation continued
- Co-interventions
- Antiplatelet agents before DOAC initiation were permitted in line with current practice at the treating physician's discretion
Mean DOAC initiation was 3.1 days after stroke onset in the early group
- Agent
- Direct oral anticoagulant (apixaban, dabigatran, edoxaban, or rivaroxaban)
- Dose
- Licensed stroke-prevention dose for the chosen DOAC; dose and route per the relevant summary of product characteristics, at physician discretion
- Route
- Oral
- Frequency
- Per product labeling for the chosen DOAC
- Duration
- Initiated 7 to 14 days after stroke onset; long-term anticoagulation continued
- Co-interventions
- Antiplatelet agents before DOAC initiation were permitted in line with current practice at the treating physician's discretion
Mean DOAC initiation was 8.3 days after stroke onset in the delayed group. Noninferiority margin was 2 percentage points (absolute); early initiation was noninferior (P=0.0003) but not superior (P=0.96)
Trial Design
Type
- Multicenter open-label blinded-endpoint phase 4 randomized trial
- Early DOAC initiation <=4 days vs delayed initiation 7-14 days
- Adults with AF-related acute ischemic stroke
- Gatekeeper design testing noninferiority then superiority
Timeline
100 UK hospitals, 2019-2024
N
3621
Enrollment
3621 patients at 100 UK hospitals (2019-2024). Multicenter open-label blinded-endpoint phase 4 randomized trial. Early DOAC within 4 days vs delayed 7-14 days. Gatekeeper design: NI tested first, then superiority. Published Lancet 2024.
ClinicalTrials.gov
NCT03759938Bedside Pearl
OPTIMAS is the largest and most definitive trial supporting early DOAC initiation after AF-related stroke. Early within 4 days was non-inferior to waiting 7-14 days, with identical 3.3% event rates. This does not mandate same-day initiation; individualize based on infarct size and hemorrhagic transformation risk. For most patients with small-to-moderate AF-related stroke without hemorrhagic transformation, starting within 4 days is well-supported by the evidence.
See also