In Ease Asia clinical trials, P2Y12 inhibitor (ticagrelor or clopidogrel) monotherapy after 3-month dual antiplatelet therapy (DAPT) resulted in a lower incidence of clinically significant bleeding, without increasing risk of major adverse cardiac and cerebrovascular events, even if acute coronary syndrome (ACS) following complex percutaneous coronary intervention (PCI) when compared with standard DAPT. Although better understood "East Asian Paradox", finding the right CYP2C19 genotype-guided P2Y12 inhibitor selection to balance maintaining ischaemic prevention and less bleeding remains a topic in real-world clinical practice.

In the PRECISE-PCI (CYP2C19 Genotype-Guided P2Y12 RECeptor Inhibitor SElection After Complex PCI) trial, the investigators aim to evaluate the safety and efficacy of CYP2C19 genotype-guided P2Y12 receptor inhibitor selection, as compared with conventional therapy in Chinese with ACS undergoing complex PCI All eligible ACS patients will be received DAPT (ticagrelor 180 mg or clopidogrel 300/600 mg plus aspirin 300 mg loading) before PCI. Subsequently to be randomly assigned into the genotype-guided group (CPY2C19 *2 or *3 carrier: ticagrelor 60 mg bid, or 45mg bid if <50 kg, ≥75 years; CPY2C19 *2 or *3 non-carrier: clopidogrel 75 mg qd in combination with aspirin 100 mg qd) and conventional group (ticagrelor 90 mg bid or clopidogrel 75 mg qd in combination with aspirin 100 mg qd). At post-PCI 3 months, both groups will be treated with mono-ticagrelor/clopidogrel without aspirin therapy for a further 9 months.

The primary endpoint is focusing on the net adverse clinical events (NACEs, a composite of cardiac death, non-fatal myocardial infarction, target vessel/lesion revascularization, stroke, or BARC-defined clinically significant bleeding type 2, 3, or 5) during 12-month follow-ups.

Inclusion Criteria:

1. Clinical Criteria:

   • Patients aged between 18-80 years old.
   • Patients with ACS (UA/NSTEMI/STEMI) undergoing PCI.
   • Patients will be treated with DAPT (P2Y12 inhibitors+aspirin) for at least 3 months.
   • Patients are willing to provide a DNA sample (via blood draw) for CYP2C19 genotyping.
   • Patients provide written informed consent before enrollment.

2. Angiographic Criteria (meet at least 1 of the following characteristics):

   • Thrombotic target lesion.
   • Calcified target lesion requiring rotational atherectomy or intravascular lithotripsy
   • Multivessel (≥2 vessels) disease will be treated.
   • Multi-target lesions (≥3 lesions) will be treated.
   • Multi-stent (≥3 stents) will be implanted.
   • Total stent length≥60 mm.
   • Bifurcation lesion requiring at least 2 stents.
   • PCI for left main.
   • PCI for chronic total occlusion.
   • PCI for bypass graft.

Exclusion Criteria:

• Patient with known CYP2C19 genotype before randomization.
• Anticipated discontinuation of clopidogrel or ticagrelor within the 12-month follow-up period.
• Planned surgery within 90 days.
• Requiring oral anticoagulation therapy (eg, atrial fibrillation, deep vein thrombosis, pulmonary thromboembolism)
• Intracranial/gastrointestinal/urogenital bleeding within 6 months.
• Active bleeding or bleeding diathesis, thrombocytopenia (platelet <100,000/mL) or hemoglobin <10 g/dL
• Hepatic dysfunction (serum liver enzyme>3 times the normal limit)
• Renal failure (eGFR <15 ml/min/1.73m2 or requiring dialysis)
• Concomitant therapy with a strong CYP3A4 inhibitor or inducer
• Life expectancy < 1 year