Precision Antiplatelet Therapy After Percutaneous Coronary Intervention Registry
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 1,643
- 试验地点
- 1
- 主要终点
- Major atherothrombotic events
研究概览
简要总结
The feasibility and clinical benefit of using a patient's genotype to guide antiplatelet therapy prescribing has been demonstrated. However, a more precise understanding of who to genotype, what to include on a genetic testing panel, and how to change antiplatelet therapy based on genotype results and other patient-specific factors is needed to optimize the impact of genotype-guided antiplatelet therapy on patient outcomes.
The Precision PCI registry is a collaboration between the University of Florida, Gainesville and Jacksonville, USA, the University of North Carolina, Chapel Hill, USA, and University of Maryland, Baltimore, USA. This registry will include a diverse population of patients who undergo Percutaneous Coronary Intervention and clinical CYP2C19 genotyping, assess clinical outcomes over 12 months and collect DNA samples for additional genotyping, and conduct pharmacodynamic analysis of platelet function in a subset of patients.
Objectives of the study:
- Define the influence of African ancestry and other patient-specific factors on clinical outcomes with genotype-guided antiplatelet therapy following PCI in a real-world setting
- Evaluate the safety and effectiveness of genotype-guided de-escalation of antiplatelet therapy (i.e., switching to less potent antiplatelet therapy) after PCI in a real-world setting
- Elucidate the effect(s) of genotypes beyond CYP2C19 on platelet reactivity and clinical outcomes with clopidogrel after PCI
详细描述
Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) is the standard of care after percutaneous coronary intervention (PCI) to reduce the risk of atherothrombotic events. Prasugrel and ticagrelor are preferred over clopidogrel in patients with an acute coronary syndrome but are associated with greater bleeding risk. The cytochrome P450 (CYP)2C19 enzyme is essential for metabolism of clopidogrel (a prodrug) to its pharmacologically active form. Approximately 30% of the U.S. population carries a CYP2C19 loss-of-function (LOF) allele that reduces the bioactivation and effectiveness of clopidogrel, but not prasugrel or ticagrelor, after PCI.
Previous studies have demonstrated the feasibility and effectiveness of incorporating CYP2C19 genotyping into clinical care to guide DAPT, with prasugrel or ticagrelor prescribed in patients with a CYP2C19 LOF allele. However, the influence of key patient-specific factors on outcomes with genotype-guided DAPT (notably African ancestry, comorbidities that impact clopidogrel effectiveness, and genotypes beyond CYP2C19) has not been defined but is critical to understand in order to optimize the clinical impact of genotype-guided DAPT. Moreover, the impact on clinical outcomes of using CYP2C19 genotype to guide de-escalation from more potent agents (e.g., prasugrel or ticagrelor) to clopidogrel in patients without a LOF allele, which has become highly clinically relevant due to more frequent initial use of prasugrel or ticagrelor after acute coronary syndrome and PCI, has not been investigated in a diverse, real-world clinical setting.
The long-term goal of this line of research is to optimize a precision medicine DAPT strategy that improves outcomes after PCI. The investigators hypothesize that multiple clinical and genetic factors jointly contribute to the effectiveness and safety of CYP2C19 LOF allele-guided selection of DAPT after PCI in a real-world clinical setting. This hypothesis will be tested by conducting a multi-center, observational study of 1,500 patients with PCI and clinical CYP2C19 genetic testing.
Aim 1: Define the influence of African ancestry and other patient-specific factors on clinical outcomes with CYP2C19 genotype-guided DAPT after PCI in a real-world setting
Aim 2: Evaluate the safety and effectiveness of CYP2C19 genotype-guided de-escalation of DAPT following PCI in a real-world setting
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •Underwent percutaneous coronary intervention for any indication
- •Had clinical CYP2C19 genotyping
- •Treated with dual antiplatelet therapy including clopidogrel, prasugrel, or ticagrelor plus aspirin or
- •Treated with a combination of a P2Y12 inhibitor i.e. clopidogrel, prasugrel or ticagrelor plus an oral anticoagulant.
排除标准
- •Managed surgically
- •Treated with thrombolysis within 48 hours
研究组 & 干预措施
Precision PCI Prospective Cohort
Patients who have undergone PCI and clinical CYP2C19 genotyping
干预措施: DNA sample collection (Other)
结局指标
主要结局
Major atherothrombotic events
时间窗: 12 months
Composite of death, myocardial infarction, ischemic stroke, stent thrombosis, and revascularization for unstable angina
次要结局
- Myocardial infarction(12 months)
- Ischemic stroke(12 months)
- Cardiovascular death(12 months)
- Stent thrombosis(12 months)
- Major adverse cardiovascular events(12 months)
- Unstable angina(12 months)
- Net clinical benefit(12 months)
- Clinically significant bleeding(12 months)
- All cause death(12 months)