High bleeding risk (HBR) patients, comprising up to 50% of those presenting with acute coronary syndrome (ACS), are a high-risk group that is increasing in size due to an aging population. The optimal selection of the potency and duration of antiplatelet therapy to reduce the risk of recurrent ischemic and bleeding events in HBR patients is still a matter of debate. Multiple strategies to reduce bleeding during secondary prevention, such as reducing the duration of dual antiplatelet therapy, using single antiplatelet therapy with a P2Y12 inhibitor, or de-escalating to a lower potency or lower-dose P2Y12 inhibitor, have been proposed. De-escalation to a lower potency or lower-dose P2Y12 inhibitor is particularly attractive because it maintains efficient pharmacological inhibition of multiple platelet pathways while potentially reducing bleeding through less aggressive activity. Yet, there has been no study comparing the effects of different de-escalation strategies with the standard potent P2Y12 inhibitors in HBR patients. The aim of the DESC-HBR study is to assess the impact of de-escalating P2Y12 inhibitor to clopidogrel 75mg, prasugrel 5mg or ticagrelor 60mg bid in HBR patients, in comparison with full-dose potent P2Y12 inhibitors, on the proportion of patients with optimal platelet reactivity (OPR). Secondary objectives involve exploring the effect of de-escalation on clinical events and patients' quality of life.