Optimal Delay Time to Initiate Anticoagulation After Ischemic Stroke in Atrial Fibrillation

Inclusion Criteria:

1. New disabling neurological deficit attributable to new ischemic stroke.
2. Minimum lesion diameter of 1.5cm on qualifying imaging. If lesion not visible onimaging, NIHSS must be greater than 4.
3. Non-valvular atrial fibrillation (paroxysmal, persistent, or permanent).
4. Not currently anticoagulated and/or will not be anticoagulated prior to starting theirNOAC at the randomized time of initiation (except for DVT prophylaxis). Note: Patients who had been taking an anticoagulant prior to their qualifying indexevent (for any reason) are eligible for START, assuming the drug is no longer having atherapeutic effect in the patient's system by 48 hours from stroke onset.
5. Treating physician plans to anticoagulate with a FDA-approved novel oral anticoagulant (NOAC): apixaban, dabigatran, edoxaban, or rivaroxaban, or other FDA-approved NOAC.
6. Qualifying brain CT or MRI scan < 48hr from stroke onset (time last known well). Ifpatient has been treated with thrombolytic or endovascular therapy for this stroke,then the qualifying scan is that which is performed after therapy to rule outclinically significant hemorrhagic transformation.
7. Ability to randomize within 60 hours of symptom onset.

Exclusion Criteria:

1. Any clinical or imaging evidence of spontaneous intracranial hemorrhage in theprevious 6 months. Note: Patients with hemorrhagic transformation of current or previous ischemic strokemay be included per Investigator's judgment. Sporadic microbleeds may be included perInvestigator's judgment. As a general recommendation, a cerebral microbleed isconsidered to be ≤ 5mm, but sometimes up to 10mm, in greatest diameter on gradientrecalled echo (GRE), or T2*, MRI sequences. Any blood visualized on a CT will beclassified as a macrobleed.
2. Infarct volume (estimated) is greater than 50% of middle cerebral artery territory onqualifying scan. If the full extent of the lesion is not visible, any patient with aNIHSS > 23 must be excluded. Note: The lesion does not need to be restricted to the mCA, but if the lesion volumeis estimated to be greater than half of the mCA territory, the patient should beexcluded. Note: In non-EVT patients, any NIHSS following the index stroke may be used to qualifythe patient for START. For example, a patient that presents with a NIHSS of 10 whothen receives tPA and improves to a NIHSS of 2 is still eligible for START. Forpatients whom had endovascular therapy, the qualifying NIHSS assessment is that whichis obtained with their qualifying scan following therapy.
3. Anticipated need for major surgery over the next 30 days that would require delay,discontinuation, or extended suspension of anticoagulant of more than 5 days.
4. Symptomatic edema expected from size and location of ischemic stroke.
5. Decreased level of consciousness present or expected.
6. Life expectancy less than 90 days.
7. Follow-up in person or by telephone for 90 days is not feasible.