Rationale: Dual antiplatelet therapy, consisting of aspirin and a P2Y12-inhibitor, reduces the risk of stent thrombosis, myocardial infarction and stroke after coronary stent implantation. Inevitably, it is also associated with a higher risk of (major) bleeding. Given the advances in stent properties, stenting implantation technique and pharmacology, it may be possible to treat patients with a single antiplatelet strategy using a potent P2Y12-inhibitor such as prasugrel or ticagrelor.

Objective: This study will serve as a pilot to investigate the feasibility and safety of a single antiplatelet strategy with prasugrel or ticagrelor prior to, during and after stent implantation in 75 patients with non-ST segment elevation acute coronary syndrome.

Study design: Single-center, single arm pilot study with a stopping rule based on the occurrence of definite stent thrombosis.

Study population: Patients presenting with non-ST segment elevation acute coronary syndrome and (a) 'de novo' lesion(s) treated with new generation drug-eluting stent(s) with adequate reduction of platelet reactivity according to platelet function testing with VerifyNow and optimal stenting result adjudicated by optical coherence tomography or coronary angiography.

Intervention: Once daily 10 mg prasugrel or twice daily 90 mg ticagrelor for 12 months preceded by a loading dose of 60 mg prasugrel or 180 mg ticagrelor at least 2 hours prior to percutaneous coronary intervention without concurrent aspirin therapy.

Main study endpoint: The primary ischemic endpoints is the composite of all-cause mortality, myocardial infarction, Academic Research Consortium defined stent thrombosis and ischemic stroke at 6 months after percutaneous coronary intervention. The primary bleeding outcome is major or minor bleeding defined as Bleeding Academic Research Consortium type 2, 3 or 5 bleeding at 6 months after percutaneous coronary intervention.

Inclusion Criteria:

• NSTE-ACS diagnosis
• 'De novo' coronary lesion(s) eligible for PCI
• Written informed consent

Exclusion Criteria:

• Known allergy or contraindication for prasugrel and ticagrelor use.
• Concurrent use of oral anticoagulants
• Overwriting indication for DAPT
• Planned surgical intervention within 12 months of planned revascularization
• PCI of left main disease, chronic total occlusion, bifurcation lesion requiring two-stent treatment, saphenous or arterial graft lesion, severely calcified lesions
• Recent or ongoing strong CYP3A4 inhibitor or inducer therapy
• Recent or ongoing therapy with CYP4A4-substrates with a narrow therapeutic index
• Pregnant or breastfeeding women at time of enrolment
• Participation in another trial with an investigational drug or device (i.e. stent)