Acute Ischemic Stroke
Conditions
Keywords
Pharmacogenetics, Cytochrome P450 2C19, Clopidogrel, Stroke
Brief summary
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.
Detailed description
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.
Interventions
DRUGGeneral principles of care and judgement of researcher
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.
Sponsors
SAMJIN PHARM
Gangnam Severance Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| composite cardiovascular events | up to 6 months | Occurrence of composite cardiovascular events (recurrent stroke, myocardial infarction, cardiovascular death) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| cardiovascular events | up to 6 months | Occurrence of ischemic stroke |
| Prognosis | 3 months | ratio of modified Rankin scale (0 - 2) at 3 months |
| early neurological worsening | up to 7 days | increased National Institutes of Health Stroke Scale within 7 day after admission) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of major adverse events | Tile frame: participants will be followed at 0, 1, 3, 6 months | Occurrence of major bleeding (fatal bleeding, symptomatic cerebral hemorrhage, ocular hemorrhage, bleeding which needs absolute bed rest or hospitalization or transfusion (more than 2 pack of whole blood or RBC). Occurrence of all-causes mortality |
Countries
South Korea
Outcome results
None listed