Angina Pectoris, Cardiovascular Disease, Chest Pain, Coronary Artery Disease, Embolism, Heart Disease, Infarction, Ischemia, Myocardial Infarction, Thrombosis, Vascular Disease
Conditions
Keywords
Clopidogrel, Ticagrelor, Prasugrel, Platelet aggregation inhibitor, Dammam University, King Fahd Hospital, Purinergic P2 receptor Antagonists
Brief summary
Clopidogrel is crucial as antiplatelet treatment in patients undergoing percutaneous coronary intervention (PCI) with stent implantation and during one year after PCI, to prevent atherothrombotic complications. However, clopidogrel is ineffective in certain patients due to genetic mutation in CYP2C19 gene a specific enzyme in the liver required for metabolism of clopidogrel. Therefore, the purpose of this study is to test these patients genetically at bedside and prescribe an alternative drug such as Ticagrelor (90 mg twice daily) or prasugrel ( 10mg once daily or 5mg once daily if the patient older than 75 years or a body weight \< 60kg) if they are carriers of the allele 2 or 3 of the mutated gene.
Detailed description
Clopidogrel is crucial as antiplatelet treatment in patients undergoing percutaneous coronary intervention (PCI) with stent implantation and during one year after PCI, to prevent atherothrombotic complications. Clopidogrel is converted into its active metabolite by Cytochrome P2C19 (CYP2C19). However 30 % of the Saudi population is carrier of the non functional CYP2C19\*2 or \*3 alleles having an impaired CYP2C19 capacity, resulting in decreased effectiveness of Clopidogrel. These patients have a 42% higher risk for major cardiovascular events (MACE) compared to non carriers. Further 50 % of the MACE occurs in the first 48 hours. Therefore Ticagrelor (90 mg twice daily) or prasugrel ( 10mg once daily or 5mg once daily if the patient older than 75 years or a body weight \< 60kg) whose actions are not dependent on conversion by CYP2C19 may be an alternative only in carriers of the non functional CYP2C19\*2 or \*3 alleles. This might be cost effective and prevent patients form MACE. Therefore the objective of this study is to assess the efficacy, complication free survival, safety and cost-effectiveness of the CYP2C19 genotype guided antiplatelet treatment strategy, using clopidogrel or prasugrel (or Ticlid). All participants will be followed for one year using follow up questionnaires.
Interventions
DRUGclopidogrel
Genotyping will be carried out using Spartan genotyping System on all intervention group and those patients who do not carry the CYP2C19 allele 2 or 3 will be given clopidogrel (75 mg per day) while all patients who carry the CYP2C19 allele 2 or 3 will be prescribed Ticagrelor (90 mg twice daily) or prasugrel ( 10mg once daily or 5mg once daily if the patient older than 75 years or a body weight \< 60kg) according to local protocol.
ticagrelor (90 mg twice daily) or prasugrel ( 10mg once daily or 5mg once daily if the patient older than 75 years or a body weight \< 60kg) according to local protocol.
Sponsors
King Fahad Armed Forces Hospital
Dammam Central Hospital
Imam Abdulrahman Bin Faisal University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Male & female age 18-70 years Inclusion Criteria: * Patient presents with acute myocardial infarction of more than 30 minutes and less than 12 hours * Patient eligible for PCI
Exclusion criteria
* Life expectancy of less than one year * Previously Known genotype * Receiving chemotherapy for malignancy * On dialysis or receiving immunosuppressive therapy or have autoimmune disease * Hepatic impairment * History of bleeding diathesis * Receiving vitamin K antagonist therapy * Confirmed hypertension * Out of normal range platelet count * History of major surgery * Severe trauma or fracture * Pregnancy and lactation * Concomitant use of simvastatin, cytochrome P450 3A4 inhibitors or inducers * Hypersensitivity to clopidogrel or ticagrelor or prasugrel
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| cardiovascular event | 1 year | The primary end point is the number of patients who develop adverse major cardiovascular event which include recurrent myocardial infarction, non-fatal stroke, cardiovascular mortality, severe ischemia, major bleeding at 30days after PCI. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | 30 days and 1 year | Secondary efficacy endpoints are the number of patients who either died , died from cardiovascular death, from cerebrovascular death, developed recurrent MI, stent thrombosis, underwent urgent target vessel revascularization, developed stroke or combination of above |
Countries
Saudi Arabia
Contacts
Primary ContactAmein K Al-Ali, PhD
Backup ContactAbdullah M Al-Rubaish, MD
Outcome results
None listed