Kosteneffectiviteit van een op het CYP2C19 genotype gebaseerde behandeling met plaatjesremmende geneesmiddelen bij patiënten met een hartinfarct die gedotterd zijn.

Rationale:

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 CYP2C19. Carriers of the non functional CYP2C19*2 and *3 alleles have an impaired CYP2C19 capacity. Clopidogrel is less effective in CYP2C19*2 and *3 carriers. For these subjects prasugrel is an alternative.



Objective:

To assess the efficacy, safety and cost-effectiveness of the CYP2C19 genotype guided antiplatelet treatment strategy, using clopidogrel or prasugrel.



Study design:

Randomized, open label, multicenter study.



Study population:

2500 ST-segment elevation myocardial infarction (STEMI) patients undergoing immediate PCI with stent implantation. All patients will receive an oral loading dose of clopidogrel of 600 mg in the ambulance, while being transported to the intervention center.



Intervention:

The intervention group will be genotyped for the CYP2C19*2 and *3 alleles within 24 hours after PCI. Carriers will receive prasugrel at a dosage of 10 mg once daily starting on the first day after the intervention for one year. Patients older than 75 years or a body weight of less than 60 kg will receive prasugrel at a dosage of 5 mg once daily. Non-carriers will be treated with clopidogrel at a dosage of 75 mg once daily from the first day and continued for one year after PCI. The control group receives clopidogrel at the same dosage as the CYP2C19*2 or *3 non-carriers of the intervention group. The follow-up duration will be one year.



Main study parameters/endpoints:

Combined endpoint of death, myocardial infarction, urgent target vessel revascularisation, stroke, stent thrombosis; bleedings; health-care resource use; quality of life assessed by the EuroQol 5D and SF36 questionnaires (and QALY’s estimated based on these questionnaires).



Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

The burden for patients participating in the study is that patients will be contacted monthly to fill out a questionnaire and will be requested three times during follow up to fill out a quality of life questionnaire. In the intervention group patients who are more likely to have a poor response to clopidogrel, based on their genotype will receive prasugrel. The efficacy of prasugrel in preventing major cardiovascular events is not genotype dependent. In de TRITON TIMI 38 study prasugrel was associated with a higher risk of developing bleeding complications. However, in a post hoc analysis in STEMI patients, bleedings in prasugrel and clopidogrel treated patients were similar.

It is hypothesized that the CYP2C19 guided antiplatelet strategy will improve treatment of patients by maximizing the efficacy in preventing serious adverse cardiac events and minimizing the risk of bleeding.

Timepoints are 30 days and 12 months following PCI.

The intervention being investigated, includes CYP2C19 genotyping, followed by a genotype guided antiplatelet treatment strategy with either prasugrel or clopidogrel on top of acetylsalicylic acid.

Patients randomized to the intervention group who carry a non functional allele will receive prasugrel while those without such an allele receive clopidogrel.

Patients in the control group will all be treated with clopidogrel in combination with acetylsalicylic acid. Antiplatelet treatment is continued for one year after PCI.