Rationale: the use of antiplatelet drugs (i.e. clopidogrel, ticagrelor or prasugrel) is crucial in the treatment of patients undergoing percutaneous coronary intervention (PCI) with stent implantation to prevent atherothrombotic events. Ticagrelor and prasugrel are more effective in preventing atherothrombotic events, but with a higher risk of bleeding complications, compared to clopidogrel. Clopidogrel is converted into its active metabolite by CYP2C19. Carriers of the non functional CYP2C19\*2 and \*3 alleles have an impaired CYP2C19 capacity, making clopidogrel less effective. For these subjects ticagrelor or prasugrel is an alternative. Objective: to assess the efficacy, safety and cost-effectiveness of the CYP2C19 genotype guided antiplatelet treatment strategy, using clopidogrel in non-carriers of a CYP2C19\*2 or \*3 allele and ticagrelor or prasugrel in carriers of a CYP2C19\*2 or \*3 allele in STEMI patients. Intervention: the intervention group will be genotyped for CYP2C19\*2 and \*3 allele variants within 48 hours after primary PCI. Carriers will receive either ticagrelor (90 mg twice daily) or prasugrel (10 mg once daily or 5 mg once daily if the patient is older than age 75 or has a body weight less than 60 kg), according to local standards. Non-carriers will be treated with clopidogrel (75 mg once daily). The control group receives either ticagrelor or prasugrel, according to local standards at the same dosage as the CYP2C19\*2 or \*3 carriers in the intervention group. The antiplatelet drug will be continued for one year after PCI. The follow-up duration will be one year using follow-up questionnaires.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
2,700
CYP2C19 genotyping will be performed in the intervention group. In patients with \*1/\*1 genotype (Extensive Metabolizer) clopidogrel will be prescribed. All patients who are carrier of a loss-to-function (\*2 or \*3) gene allel and all patients randomized to the control group will be prescribed prasugrel or ticagrelor, according to local protocol.
OLV Hospital
Aalst, Belgium
University of Naples Federico II
Naples, Italy
Meander Medisch Centrum
Amersfoort, Netherlands
OLVG
Amsterdam, Netherlands
Rijnstate Hospital
Arnhem, Netherlands
Amphia Hospital
Breda, Netherlands
University Medical Center Groningen
Groningen, Netherlands
St. Antonius Hospital
Nieuwegein, Netherlands
University Medical Center
Utrecht, Netherlands
Isala Klinieken
Zwolle, Netherlands
Net clinical benefit
The primary endpoint is the number of patients who either died, developed a recurrent myocardial infarction (MI), developed definite stent thrombosis, stroke or PLATO major bleeding at 1 year after PCI.
Time frame: 1 year
Safety endpoint
The primary safety endpoint is the number of patients with PLATO major or minor bleeding at 1 year after PCI.
Time frame: 1 year
Pharmacoeconomics endpoint
The primary endpoints in terms of pharmacoeconomics are quality of life, direct medical costs e.g. costs for blood transfusions, drugs, hospitalization and non-medical costs e.g. costs incurred due to sickness absence.
Time frame: 1 year
Net clinical benefit at 30 days
The number of patients who either died, developed a recurrent myocardial infarction (MI), developed definite stent thrombosis, stroke or PLATO major bleeding at 30 days after PCI.
Time frame: 30 days
Secondary efficacy and safety endpoint
both efficacy and safety will be studied in more detail, using the items of the primary endpoint (death, recurrent myocardial infarction, stentthrombosis, stroke, PLATO major bleeding) as separate parameters and in different combinations, adding cardiovascular and cerebrovascular death, probable and possible stent thrombosis, urgent target vessel revascularization (uTVR) and hospital admission for acute coronary syndrome (ACS) to the efficacy analysis, and (non-)CABG-related bleeding, major-, minor-, life threatening-, fatal-, intracranial and bleeding requiring transfusion to the bleeding analysis, both for 30 days and 1 year follow-up
Time frame: 30 days and 1 year
Secondary safety endpoint
Number of patients with bleeding events in 1 year follow up, not only using PLATO bleeding classification, but also, TIMI and BARC bleeding classifications to make the study comparable to previous and future publications
Time frame: 30 days and 1 year
Drug endpoint
Comparing the number of patients switching from the recommended P2Y12 inhibitor to a different P2Y12 inhibitor and the number of patients who discontinue the P2Y12 inhibitor early in both the control and genotype group
Time frame: 30 days and 1 year
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