Genotyping Guided Individualized Treatment of Clopidogrel and Ticagrelor in ACS

Study of Clopidogrel and Ticagrelor Anti-Platelet Treatment Using an Individualized Strategy Based on Genotyping in Chinese ACS Patients

Clopidogrel, in addition to aspirin, is the cornerstone of therapy in patients suffering from Acute coronary syndrome. However, the platelet inhibitory response to clopidogrel varies substantially among individuals. Several loss-of-function polymorphisms have been identified that may influence clinical outcome in patients presenting with acute coronary syndromes (ACS) who are treated with clopidogrel. However their contribution to high on-treatment platelet reactivity (HPR) in clopidogrel treated Chinese patients is less known. As far as we know, ticagrelor is not dependent on gene-based metabolic activation and demonstrated greater clinical efficacy than clopidogrel in a recent secondary prevention trial. we will conduct an interventional study to compare the antiplatelet efficiency between clopidogrel and ticagrelor by the guidance of CYP450 2C19*2 (CYP2C19*2) , using Taqman genotyping method.

Clopidogrel, in addition to aspirin, is the cornerstone of therapy in patients suffering from Acute coronary syndrome. However, the platelet inhibitory response to clopidogrel varies substantially among individuals. Several loss-of-function polymorphisms have been identified that may influence clinical outcome in patients presenting with acute coronary syndromes (ACS) who are treated with clopidogrel.

Mounting evidence suggests a crucial role for the loss-of-function CYP2C19*2 genetic variant. Carriers of CYP2C19*2 allele were at 30% higher risk for major adverse clinical events compared to non-carriers. CYP2C19*2 alone was also associated with increased mortality and stent thrombosis. These findings led the American Food and Drug Administration to issue a boxed warning for clopidogrel stating that poor metabolizers may not receive the full benefit of the drug. Thus, routine genotyping in the context of dual anti-platelet therapy is necessary.

Individual dual anti-platelet treatment is feasible to give the presence of treatment alternatives such as ticagrelor that is not dependent on gene-based metabolic activation and demonstrated greater clinical efficacy than clopidogrel. Individualized administration of ticagrelor may have the potential to successfully minimize adverse ischemic events.

200 patients undergoing percutaneous coronary intervention (PCI) for treatment of non-ST-elevation acute coronary syndrome or stable coronary artery disease will be eligible for enrollment. Patients will be randomly assigned to a strategy of genotyping(using Taqman genotyping method) or standard treatment . CYP2C19*2 carriers will be given 90 mg ticagrelor twice daily, and non-carriers and patients in the standard treatment group will be given 75 mg clopidogrel daily. At the end of the 5 day antiplatelet treatment, efficacy of the treatment strategies will be evaluated using light transmittance aggregometry (LTA) method.

Inclusion Criteria:

The diagnosis of ACS including unstable angina (UA),non-ST elevation myocardial infarction(NSTEMI),and ST-elevation MI (STEMI) is according to the American Heart Association/American College of Cardiology (AHA/ACC) criteria

Exclusion Criteria:

known contraindication to dual anti-platelet therapy, history of chronic inflammatory disease, steroidal and non-steroidal anti-inflammatory drugs use, previous administration of antiplatelet drugs within 1 month before coronary artery angiography, illicit drug abuse, significant bleeding, cerebrovascular event within 3months, and/or major surgery within 4 weeks.