ACS - Acute Coronary Syndrome, CYP2C19 Polymorphism
Conditions
Keywords
CYP2C19 Genotype, P2Y12 Receptor Inhibitor, Complex PCI
Brief summary
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.
Detailed description
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.
Interventions
DRUGCYP2C19 Genotype Guided DAPT
Patients with \*2 or \*3 carrier will be received ticagrelor 60mg or 45mg bid (if \<50 kg, ≥75 years) + aspirin 100 mg qd; Patients with \*2 or \*3 non-carrier will be received clopidogrel 75mg qd + aspirin 100 mg qd
Patients will be conventionally received ticagrelor 90mg bid or clopidogrel 75mg qd + aspirin 100 mg qd
Sponsors
Zunyi Medical College
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| NACE (net adverse clinical event) | At 12 months | The incidence of NACE (composite of cardiac death, non-fatal myocardial infarction, target vessel/lesion revascularization, stroke, or clinically significant bleeding according to BARC criteria). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of clinically significant bleeding | At 12 months | The Bleeding Academic Research Consortium (BARC)-defined clinically significant bleeding (type 2, 3, or 5 bleeding) as follows: Type 2: Any overt, actionable sign of hemorrhage, requiring nonsurgical, medical intervention by a healthcare professional; Leading to hospitalization or increased level of care; Prompting evaluation. Type 3: Clinical, laboratory, and/or imaging evidence of bleeding with specific healthcare provider responses. Type 3a: Overt bleeding plus hemoglobin drop of 3 to 5 g/dL; Any transfusion with overt bleeding. Type 3b: Overt bleeding plus hemoglobin drop ≥5 g/dL; Cardiac tamponade; Bleeding requiring surgical intervention for control; Bleeding requiring intravenous vasoactive agents. Type 3c: Intracranial hemorrhage; Subcategories confirmed by autopsy or imaging or lumbar puncture; Intraocular bleed compromising vision. Type 5: Fatal bleeding is bleeding that directly causes death with no other explainable cause. |
| Incidence of MACCE | 12 months | The incidence of major adverse cardiac and cerebrovascular event (MACCE), is composite of cardiac death, non-fatal myocardial infarction, target vessel/lesion revascularization, or stroke. |
Countries
China
Contacts
Primary ContactCai De Jin, MD
Backup ContactYan Yan Jin, MD
Outcome results
None listed