Personalized Antiplatelet Secondary Stroke PRevenTion

This is a descriptive study designed to evaluate the safety and feasibility of a precision medicine approach to antiplatelet selection for secondary stroke prevention.

Subjects meeting inclusion/exclusion criteria will be randomly assigned to: (1) the treatment group where antiplatelet medications will be selected using platelet function phenotype and/or key pharmacogene genotypes (2) the control group where participants will receive standard care for antiplatelet therapy (without knowledge of phenotype or genotype).

Eligibility Criteria:
Inclusion Criteria:

* Provide signed and dated informed consent form.
* Willing to comply with all study procedures and be available for the duration of the study.
* Meet criteria for a mild or moderate ischemic stroke or high-risk TIA
* Ability to randomize within 30 hours of stroke symptom onset/last seen normal time

Exclusion Criteria:

* Evidence of new or prior non-traumatic intracerebral hemorrhage, subarachnoid hemorrhage, or subdural hemorrhage on initial head CT
* Evidence of a central nervous system tumor, abscess, intracranial aneurysm or vascular/structural malformation, or any neuro-inflammatory, neuro-infectious, or neurodegenerative disorder on neuroimaging or exam that could confound a participant's functional outcome
* Isolated or pure sensory symptoms (e.g., numbness), visual changes, or "dizziness"/vertigo without evidence of acute ischemic stroke on baseline head CT or MRI.
* Qualifying ischemic event is believed to be iatrogenic or procedure related
* Required to take a specific antiplatelet medication for an indication other than ischemic stroke during the study period that would prevent the investigator from following the study algorithm
* Etiology of qualifying ischemic event is known to be cardioembolic
* High likelihood that anticoagulation will be needed during the study period.
* High likelihood that carotid endarterectomy or carotid stenting will occur during the period of the study.
* Pre-stroke modified Rankin scale (mRS) score ≥ 3
* Evidence of frailty
* Contraindication to aspirin, clopidogrel, Aggrenox®, or ticagrelor
* Known allergy or hypersensitivity that would prevent the investigator from following the study algorithm
* Any history of moderate to severe drug-induced adverse events
* Renal insufficiency or history of kidney transplant
* Hepatic impairment, international normalized ratio (INR) \> 1.5, physical manifestations of liver disease, or history of liver transplant
* Class II, III, or IV New York Heart Association (NYHA) functional heart failure
* Any history of bradycardia without pacemaker placement
* Active obstructive lung disease
* Any active hematologic disorder
* Active bleeding diathesis
* Any systemic hemorrhage or GI bleed in the 3 months prior to the qualifying stroke
* Active peptic ulcer disease
* Women who self-report that they are pregnant or breastfeeding
* Active alcohol or substance abuse or dependence
* Inability or failure to provide informed consent.
* Inability of the patient to adhere to study procedures and/or follow-up, in the opinion of the investigative team
* Inability to swallow oral medications
* Not willing or able to discontinue prohibited concomitant medications
* Ongoing participation in another non-observational clinical study
* Life expectancy \< 1 year, in the opinion of the investigative team