The primary objective of this trial is to assess the effects of ticagrelor plus aspirin versus clopidogrel plus aspirin on reducing the 3-month risk of any stroke (both ischemic and hemorrhagic, primary outcome) when initiated within 24 hours of symptom onset in CYP2Y19 LOF alleles carriers with TIA or minor stroke.

According to the Global Burden of Disease(GBD) Study 2016, China bears the greatest lifetime risk of stroke from 25-year-age onward. Minor ischemic events, including minor stroke and TIA, were major parts of stroke manifestations. Events (CHANCE) has shown that 21-day dual antiplatelet therapy (clopidogrel and aspirin) compared to aspirin alone which initiated within 24 hours after symptoms onset would reduce 32% risk of stroke recurrence within 90 day, but not in carriers of CYP2C19 loss-of-function (LOF) alleles. The primary purpose of this study is to compare ticagrelor plus aspirin with clopidogrel plus aspirin on reducing the 3-month risk of any stroke (both ischemic and hemorrhagic, primary outcome) when initiated within 24 hours of symptom onset in CYP2Y19 LOF alleles carriers with TIA or minor stroke.

Both intent analysis (ITT) and compliance program set (PPS) were used for analysis.

We will use Kaplan-Meier estimates of the cumulative risk of stroke (ischemic or hemorrhagic) event during maximum 90-day follow-up, with hazards ratios and 95% CI calculated using Cox proportional hazards methods and the log-rank test to evaluate the treatment effect. All statistics will be 2-sided with P<0.05 considered significant, accounting for interim analyses.

All patients who received study drugs and with at least one safety follow-up record will be included in the safety population. The data for safety evaluation included adverse reactions observed during the trial and changes in laboratory data before and after treatment.

Inclusion Criteria

1. 40 years or older than 40 years；

2. Acute cerebral ischemic event due to：

   • Acute non-disabling ischemic stroke (NIHSS≤3 at the time of randomization)or，
   • TIA with moderate-to-high risk of stroke (ABCD2 score ≥ 4 at the time of randomization)；

3. Can be treated with study drug within 24 hours of symptoms onset*(*Symptom onset is defined by the "last seen normal" principle)；

4. CYP2C19 loss-of-function allele carriers；

5. Informed consent signed.

Exclusion Criteria

1. Malformation, tumor, abscess or other major non-ischemic brain disease (e.g., multiple sclerosis) on baseline head CT or MRI.

2. Isolated or pure sensory symptoms (e.g., numbness), isolated visual changes, or isolated dizziness/vertigo without evidence of acute infarction on baseline head CT or MRI.

3. Iatrogenic causes (angioplasty or surgery) of minor stroke or TIA.

4. Preceding moderate or severe dependency (modified Rankin scale [mRS] score 3-5).

5. Contraindication to clopidogrel, ticagrelor or aspirin

   • Known allergy
   • Severe renal (creatinine exceeding 1.5 times of the upper limit of normal range) or hepatic (ALT or AST > twice the upper limit of normal range) insufficiency
   • Severe cardiac failure (NYHA level: III to IV)
   • History of hemostatic disorder or systemic bleeding
   • History of thrombocytopenia or neutropenia
   • History of drug-induced hematologic disorder or hepatic dysfunction
   • Low white blood cell (<2×109/L) or platelet count (<100×109/L)

6. Hematocrit (HCT) <30%

7. Clear indication for anticoagulation (presumed cardiac source of embolus, e.g., atrial fibrillation, prosthetic cardiac valves known or suspected endocarditis)

8. History of intracranial hemorrhage or amyloid angiopathy

9. History of aneurysm (including intracranial aneurysm and peripheral aneurysm)

10. History of asthma or COPD (chronic obstructive pulmonary disease)

11. High-risk for bradyarrhythmia (first-degree or second-degree AV block caused by sinus node disease, and brady-arrhythmic syncope without pacemaker)

12. History of hyperuricemia nephropathy

13. Anticipated requirement for long-term (>7 days) non-steroidal anti-inflammatory drugs (NSAIDs)

14. Planned or likely revascularization (any angioplasty or vascular surgery) within the next 3 months

15. Scheduled for surgery or interventional treatment requiring study drug cessation

16. Severe non-cardiovascular comorbidity with life expectancy < 3 months

17. Inability to understand and/or follow research procedures due to mental, cognitive, or emotional disorders

18. Dual antiplatelet treatment (or more than two antiplatelet agents) in 72 hours before randomization

19. Current treatment (last dose given within 10 days before randomization) with heparin therapy or oral anti coagulation

20. Intravenous thrombolytic therapy (such as intravenous rtPA) or mechanical thrombectomy within 24 hours prior to randomization

21. Gastrointestinal bleed within 3 months or major surgery within 30 days

22. Diagnosis or suspicious diagnosis of acute coronary syndrome

23. Participation in another clinical study with an experimental product during the last 30 days

24. Currently receiving an experimental drug or device

25. Pregnant, currently trying to become pregnant, or of child-bearing potential and not using birth control

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)