Assessment of an Early De-Escalation to a Low-potency Single Antiplatelet Therapy Guided by Genetics Versus a Systematic High-Potency Single Antiplatelet Therapy to Neutralize Bleeding Complications in Patients With High Bleeding Risk Beyond One Month After an Acute Coronary Syndrome

Multicenter, randomized, open label trial using the PROBE study design. Randomization 1 to 3 months (preferably 1, considering the HBR) after ACS into 2 parallel arms. Stratification: according to revascularization status (PCI or no PCI), genotype (loss of function, fast metabolization, none) and center.

Control arm: stop aspirin for a single antiplatelet therapy with a high-potency antiplatelet (ticagrelor or prasugrel).

Intervention arm: single-antiplatelet with a low-potency antiplatelet (aspirin or clopidogrel) guided by genetic testing.

Inclusion criteria

• Being 18-year-old or older
• Admission for type 1 acute myocardial infarction (STEMI or NSTEMI)
• Bedside genetic testing for clopidogrel resistance that can be performed during hospital stay for ACS (oral swab kit with result within 1 hour)
• Treated with aspirin and ticagrelor, or aspirin and prasugrel at the screening phase and at the randomization visit.
• High bleeding risk as defined below (criteria adapted from the Consensus Document From the Academic Research Consortium for High Bleeding Risk) (at least one criterion) :

• Age ≥75 years old.
• Baseline haemoglobin <11 g/dl (or anaemia requiring transfusion during the 4 weeks prior to randomization).
• Chronic Kidney Disease with estimated glomerular filtration rate ≤ 30 ml/min.
• Thrombocytopenia with platelet count < 100 x 109 / L
• Chronic bleeding diatheses: inherited or acquired conditions known to be associated with increased bleeding risk such as platelet dysfunction, von Willebrand disease (prevalence of 1%-2% in the general population), inherited or acquired clotting factor deficiencies (including factors VII, VIII [hemophilia A], IX [hemophilia B], and XI), or acquired antibodies to clotting factors, among others.
• Cirrhosis with portal hypertension.
• PCI after major traumatism or surgery.
• Any documented stroke in the last 12 months.
• Hospital admission for bleeding or transfusion within last 6 months.
• Nonskin cancer diagnosed or treated ≤3 years.
• Planned daily nonsteroidal anti-inflammatory drugs (other than aspirin) or steroids for ≥30 days after PCI.
• patient affiliated to a social security system
• signed informed consent form
• Women of childbearing capacity with effective contraception for the duration of the research OR man, OR woman not of childbearing capacity

Exclusion criteria

• Currently participating in any interventional investigational device or drug trial
• Any prior documented intracerebral bleed
• Contra-indication, known allergy or expected interactions with clopidogrel. Baseline treatment (at screening) should not include an antiplatelet therapy for which a contra-indication, known allergy or expected interactions is known (example history of stroke and use of prasugrel, or concomitant use of ticagrelor and ritonavir)
• Patients on concomitant treatment with an anticoagulant agent (Vitamin-K antagonists or novel oral anticoagulants such as rivaroxaban, dabigatran or apixaban)
• Planned surgery within 12 coming months
• Patient under guardianship or curatorship
• Pregnancy or breastfeeding
• Inability to sign the informed consent form