Personalized Antiplatelet 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).

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