De-escalating Antiplatelet Therapy to Assess Platelet Reactivity and Outcomes in High Bleeding Risk Patients With Recent ACS

Participants fulfilling all the following inclusion criteria are eligible for the study:

• Informed Consent signed and dated.

• Patients deemed at HBR according to standard definitions (i.e. PRECISE-DAPT ≥25 or HBR-ARC with at least 1 major or 2 minor criteria).

• Treated with PCI due to a recent ACS (i.e. unstable angina, non-ST segment elevated myocardial infarction or ST segment elevated myocardial infarction) 30 ±7 days earlier.

• Treated with DAPT with full-dose potent P2Y12 inhibitors (e.g. prasugrel 10mg or ticagrelor 90mg bid) according to international guidelines recommendations.

The presence of anyone of the following exclusion criteria will lead to exclusion of the participant:

• Age < 18 years

• Known intolerance, hypersensitivity or contraindication (including active bleeding) to aspirin, clopidogrel, prasugrel, ticagrelor or to any of the excipients

• Indication to oral anticoagulation

• Indication to prolonged treatment with full-dose potent P2Y12 inhibitors (e.g. previous stent thrombosis, stenting of last remaining vessel, stent with indication for longer-term DAPT, perceived very high coronary ischemic risk)

• Any planned major surgery or interventional procedure requiring treatment modification

• Prior transient ischemic attack, ischemic or haemorrhagic stroke

• Severe hepatic insufficiency (Child-Pugh class C)

• Ongoing therapy with strong CYP3A inducers or strong CYP3A inhibitors (e.g. ketoconazole, clarithromycin, nefazodone, ritonavir, atazanavir etc.)

• Women who are pregnant, breast feeding or of childbearing potential (i.e. fertile, following menarche and who are not surgically sterile, including hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or post-menopausal defined as no menses for 12 months without an alternative medical cause); Participation in another study with investigational drug within the 30 days, or 5 half-lives of the study drug whichever is longer, preceding and during the present study

• Enrolment of the investigator, his/her family members, employees

• Inability to follow the procedures of the study (language problems, mental disorders, dementia) or comorbidities associated with less than 12 months-life expectation (active malignancies drug or alcohol abuse, etc.) or other conditions that might result in protocol non-compliance.