Table 2:
Summary of ongoing randomised controlled trials investigating early versus late initiation of direct oral anticoagulant treatment in patients with recent atrial fibrillation-related ischaemic stroke.
| Planned sample size | Intervention (early initiation of anticoagulant treatment) | Control (late initiation of anticoagulant treatment) | Follow-up period | Primary outcome | Patients with haemorrhagic transformation included | NIHSS exclusion criteria | Estimated end of study | |
|---|---|---|---|---|---|---|---|---|
| ELAN (NCT03148457) |
2000 | <48 h after symptom onset (minor and moderate stroke) or at day 6 (±1 day) after symptom onset (major stroke)* | Current recommendations (ie, minor stroke after day 3 [±1 day], moderate stroke after day 6 [±1 day] and major stroke after day 12 [±2 days])* | 30 days (secondary outcomes after 90 days) | Composite outcome (major bleeding, recurrent ischaemic stroke, systemic embolism, or vascular death, or a combination of these outcomes) | Yes | No exclusion criteria | October 2021 |
| OPTIMAS (EudraCT, 2018-003859-38) |
3474 | ≤4 days after acute ischaemic stroke | 7–14 days after acute ischaemic stroke | 90 days | Composite outcome at 90 days (combined incidence of recurrent symptomatic ischaemic stroke, symptomatic intracranial haemorrhage [including extradural, subdural, subarachnoid and intracerebral haemorrhage, and haemorrhagic transformation of the qualifying infarct], and systemic embolism) | Yes | No exclusion criteria | 2021–22 |
| TIMING (NCT02961348) |
3000 | ≤4 days after acute ischaemic stroke | 5–10 days after acute ischaemic stroke | 90 days | Composite outcome (recurrent ischaemic stroke, symptomatic intracerebral haemorrhage, or all-cause mortality, or a combination of these outcomes) | Yes | No exclusion criteria | December 2020 |
| START (NCT03021928) |
1500 (1000 patients with mild or moderate stroke, 500 with severe stroke)† | Time-to-treatment delay of 3, 6,10, or 14 days for mild or moderate stroke; 6,10,14, or 21 days for severe stroke† | Time-to-treatment delay of 3, 6,10, or 14 days for mild or moderate stroke; 6,10,14, or 21 days for severe stroke† | 30 days (secondary outcomes after 90 days) | Composite of any CNS haemorrhagic or other major haemorrhagic events and the ischaemic events of stroke or systemic embolism within 30 days of the index stroke | Yes | Score >3 and score <23 | August 2021 |
NIHSS= National Institutes of Health Stroke Scale. ELAN=Early Versus Late Initiation of Direct Oral Anticoagulants in Post-ischaemic Stroke Patients with Atrial fibrillation. OPTIMAS=OPtimal TIMing of Anticoagulation after AF-associated acute cardioembolic ischaemic Stroke. TIMING=Timing of oral anticoagulant therapy in acute ischemic stroke with atrial fibrillation. START=Optimal Delay Time to Initiate Anticoagulation After Ischemic Stroke in Atrial Fibrillation.
Small infarct size is defined by lesions smaller than 1·5 cm in the anterior or posterior circulation; medium infarct size by lesions in a cortical superficial branch of middle cerebral artery (MCA), in the MCA deep branch, in the internal border zone territories, in a cortical superficial branch of posterior cerebral artery, or in a cortical superficial branch of the anterior cerebral artery; large infarct size by lesions that involve the complete territory of MCA, posterior cerebral artery, or anterior cerebral artery, in two cortical superficial branches of MCA, in a cortical superficial branch of MCA associated to the MCA deep branch, or in more than one artery territory.
Minor stroke is defined by a NIHSS score <8, mild stroke by a NIHSS score of 8–15, and severe stroke by a NIHSS score >15, as per the European Society of Cardiology and European Heart Rhythm Association definitions (panel 1).