Clopidogrel Preventive Effect Based on CYP2C19 Genotype in Ischemic Stroke

Gangnam Severance Hospital2,927 enrolled

Overview

The hypothesis of this study is that "the poor metabolizer or intermediate metabolizer of the cytochrome P450 2C19 genotype in patients with acute ischemic stroke is associated with increased risk of composite cardiovascular events (recurrent stroke, myocardial infarction, cardiovascular death) compared to those who of extensive metabolizer of the cytochrome P450 2C19 genotype".

Clopidogrel, one of the antiplatelet agents used for secondary prevention in patients with ischemic stroke and coronary artery disease, has been shown to have a superior antiplatelet effect compared to aspirin, and is therefore being administered to many patients with stroke and coronary artery disease. Clopidogrel inhibits platelet-derived ADP receptor, P2Y12, in the liver to produce an anti-platelet effect. It has been suggested that clopidogrel resistance could be occurred from drug-drug interaction via the same pharmacological metabolic pathway. Previous studies reported that the genotypes of Cytochrome P450 2C19, which is involved in the metabolism of clopidogrel in the liver, lead to differences in drug response and recurrence rates of cardiovascular disease. The risk of recurrence of ischemic stroke was reported to be about 4 times higher in patients with a poor metabolizer or intermediate metabolizer genotype of the Cytochrome P450 2C19 genotype compared to the extensive metabolizer genotype. This genotypes of Cytochrome P450 2C19 were also different according to race. The researches about cytochrome P450 2C19 genotype and clopidogrel resistance have been conducted mainly in patients with coronary artery disease and are not known in stroke patients. Few studies have examined whether the resistance of clopidogrel according to the genotype of cytochrome P450 2C19 in stroke patients is related to the occurrence and/or recurrence of cardiovascular disease. The hypothesis of this study is that "the poor metabolizer or intermediate metabolizer of the cytochrome P450 2C19 genotype in patients with acute ischemic stroke is associated with increased risk of cardiovascular disease and mortality compared to those who of extensive metabolizer of the cytochrome P450 2C19 genotype".

Study Type

OBSERVATIONAL

Enrollment

2,927

Conditions

Acute Ischemic Stroke

Interventions

General principles of care and judgement of researcherDRUG

Because our study will be performed by observational design, there will be no intervention for our study. Because it is a registry-based study, overall decision making for medications will be performed according to the general principles of care and judgement of researcher.

Eligibility

Sex: ALLMin age: 19 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Ischemic stroke confirmed by brain CT or MRI 2. Patient who received clopidogrel within 72 hours after onset of ischemic stroke 3. Adults over 19 years 4. Patients who agreed to participate in this study within 7 days after ischemic stroke 5. Patients who underwent Cytochrome P450 2C19 genotype test. Exclusion Criteria: 1. Patients who currently take anticoagulation or is expected to take anticoagulation with 6 months from the screening date 2. Patients who need other antiplatelet drugs except aspirin and clopidogrel 3. Patients who were taking clopidogrel prior to ischemic stroke 4. Patients scheduled for coronary artery stenting, coronary artery bypass surgery, carotid endarterectomy, carotid and cerebral artery stenting 5. Patients with severe comorbidities or active cancer with an estimated life expectancy of less than two years 6. Patients who participated in other drug clinical trials within the past 30 days 7. Patients with high risk source of potential cardiac source of embolism in TOAST classification 8. Patients who are expected to unable to participate or continue the study

Locations (37)

Outcomes

Primary Outcomes

composite cardiovascular events

Occurrence of composite cardiovascular events (recurrent stroke, myocardial infarction, cardiovascular death)

Time frame: up to 6 months

Secondary Outcomes

cardiovascular events

Occurrence of ischemic stroke

Time frame: up to 6 months

cardiovascular events

Occurrence of transient ischemic attack

Time frame: up to 6 months

cardiovascular events

Revascularization of cerebral, coronary, peripheral artery or aorta

Time frame: up to 6 months

cardiovascular events

Occurrence of myocardial infarction

Time frame: up to 6 months

early neurological worsening

increased National Institutes of Health Stroke Scale within 7 day after admission)

Time frame: up to 7 days

Prognosis

ratio of modified Rankin scale (0 - 2) at 3 months

Time frame: 3 months

Data from ClinicalTrials.gov

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Yongin-si, Gyeonggi-do, South Korea

Department of Neurology Korea University Ansan Hospital

Ansan, South Korea

Department of Neurology Hallym University Sacred Heart Hospital

Anyang, South Korea

Department of Neurology Inje University Busan Paik Hospital

Busan, South Korea

Department of Neurology Dong-A University Hospital

Busan, South Korea

Department of Neurology Kosin University Gospel Hospital

Busan, South Korea

Department of Neurology Changwon Fatima Hospital

Changwon, South Korea

Department of Neurology Hallym University Chuncheon Sacred Heart Hospital

Chuncheon, South Korea

Department of Neurology Kangwon National University Hospital

Chuncheon, South Korea

Department of Neurology Keimyung University Dongsan Hospital

Daegu, South Korea

...and 27 more locations