Stroke is a common cause of disability. The most common type of stroke, an ischemic stroke, is caused by a blood vessel in the brain getting blocked by a clot. When this happens, part of the brain is damaged because it is not getting the blood supply it needs. To treat this type of stroke, doctors give medication and/or do a procedure to remove the blockage and restore blood supply to the brain.

Unfortunately, patients who have had an ischemic stroke are at higher risk of having another ischemic stroke. This risk is highest in the first 21 days after a stroke. Currently, doctors give patients the medication aspirin every day, starting 24 hours after stroke treatment, to prevent recurrent strokes. However, some studies have shown that giving another medication, clopidogrel, in addition to aspirin, is safe and may work better than aspirin alone at preventing repeat strokes. Both aspirin and clopidogrel are a type of medication called an antiplatelet that prevents clots from forming in the blood. When both medications are given together, it is called dual antiplatelet treatment. The main risk of antiplatelet medications is bleeding.

This research aims to study the safety and feasibility of using dual antiplatelet treatment to prevent recurrent strokes. Patients who have received treatment for an ischemic stroke will first be screened to rule out patients at high risk of bleeding. Following informed consent, patients at low risk of bleeding will be enrolled in the study 24 hours after their initial stroke treatment. Patients will be randomly assigned to either take aspirin alone or aspirin and clopidogrel for 21 days for recurrent stroke prevention. The study team will then follow patients for three months after treatment to collect information about their recovery and assess differences between the two groups.

Inclusion Criteria:

1. Participants must be >18 years of age at the time of randomization
2. Acute non-cardioembolic ischemic stroke in the anterior circulation treated with reperfusion therapy defined as intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT)
3. Time from end of acute reperfusion therapy to randomization ≤ 24 hours
4. Mild to moderate deficit defined as a National Institute of Health stroke scale of ≤11 at the time of randomization
5. At least one non-contrast CT scan completed post reperfusion therapy and prior to randomization without any hemorrhage (including hemorrhagic infarction) and/or contrast extravasation.
6. Premorbid mRS less than or equal to 2
7. Signed informed consent from the patient or legally authorized representative

Exclusion Criteria:

1. Any known disorder associated with a significantly increased risk of bleeding
2. Post-reperfusion CT scan ASPECT score <8.
3. Anticoagulation is required for any indication other than DVT prophylaxis
4. Evidence-based indication for dual antiplatelet therapy
5. Planned surgical intervention in the next 90 days includes but is not limited to carotid endarterectomy, where dual antiplatelet is not indicated, and carotid stenting, where single antiplatelet is not used.
6. History of intracranial or subarachnoid hemorrhage
7. Intracranial tumour, arteriovenous malformation or aneurysm;
8. Intracranial or spinal cord surgery within three months;
9. Gastrointestinal or urinary tract hemorrhage within the previous 21 days;
10. Coagulation disorder, thrombocytopenia <100, 000/mm3, and Prothrombin time INR ≥1.8
11. Index stroke is caused by infective endocarditis, dissection, systematic or central nervous system vasculitis
12. History of active malignancy being treated or life expectancy ≤ 90 days
13. Allergy to clopidogrel or aspirin
14. Pregnancy
15. Participation in another clinical trial.
16. The presence of a major co-morbid illness that would make it unlikely that the participant will be able to complete follow-up

IPD will be available to investigators in consultation with the principal investigators