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.

Inclusion Criteria:

• more than 21 years of age with symptoms of acute myocardial infarction of more than 30 minutes but less than 12 hours
• performed primary PCI with stenting for STEMI

Exclusion Criteria:

• unable to give informed consent or have a life expectancy of less than one year
• active malignancy with increase in bleeding risk, in the investigator's opinion
• women who are known to be pregnant or who have given birth within the past 90 days or who are breastfeeding
• having received thrombolytic therapy within the previous 24 hours or oral anticoagulants during the previous 7 days
• severe renal function impairment needing dialysis
• confirmed or persistent severe hypertension (Systolic Blood Pressure (SBP) > 180 mmHg and/or Diastolic Blood Pressure (DBP) >110 mmHg) at randomization
• contraindication to anticoagulation or at increased bleeding risk, at the investigator's opinion
• cardiogenic shock (SBP ≤ 80mmHg for >30 mins) or Intra-Aortic Balloon Pump (IABP) placed
• history of major surgery, severe trauma, fracture or organ biopsy within 90 days prior to randomisation
• clinically significant out of range values for platelet count or haemoglobin level at screening, in the investigator's opinion.