In last ten years significant changes in the clinical epidemiol- ogy of acute coronary syndromes (ACS) have taken place. Despite the progressive reduction of in-hospital mortality, paradoxically, the post-hospital mortality has significantly increased [1-4]. This new trend in the epidemiology of coronary artery disease (CAD) has been largely attributed to the implementation of treatments of the acute phase of myocardial infarction (MI). As a consequence, the rising number of survivors has progressively increased the population at high risk of recurrences (major adverse cardiovascu- lar events, MACE). This new scenario we are facing with, that was once called “stable” ischemic heart disease, is no longer to be considered as such. Both heart failure (HF) and the residual high atherothrombotic risk (HTR) [1,5] have been identified as the major independent predictors of recurrent MACEs. HTR can be detected both by clinical factors, such as diabetes mellitus, renal failure, peripheral artery disease, a history of angina or previous acute myocardial infarction (AMI), and by anatomical/surgical factors as the presence of multivessel disease, especially if treated with incomplete revascularization, or no revascularized at all. Both observation from registries [4,6] and epidemiological studies [1] show that patients with HTR may present with MACEs even far from the index event. In an Italian National retrospective cohort study from the administrative database of the National Health Institute that recruited 186.646 patients admitted for a MI from 2009 to 2010 in all the Italian hospitals, the risk of MACE remained high over 5 years after a first MI in patients with HTR. High residual risk had been defined, as commonly in most current studies, by at least one of the following: previous MI, vascular dis- ease, type 2 diabetes mellitus or renal failure (GFR< 60 ml/min/1.73 m2) [7]. Intervention studies as the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction) [8,9] and the Dual Antiplatelet Therapy Study [10] have con- firmed observational and epidemiological data. Prolonged dual antiplatelet therapy (DAPT) for up to three years yielded a prog- nostic benefit in selected patients at very high risk of ischemic recurrences. The IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) and nowadays the FOURIER [11] and ODYSSEY outcomes [12] have reinforced the notion that lowering the LDL-cholesterol level leads to a reduc- tion in CV events continous, linear without any apparent thresh- old, emphasizing the need for long-term intensive secondary pre- vention in subgroups of patients with high residual atherothrom- botic risk. Finally, in the recent COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) [13], combination of aspirin and rivaroxaban at “vascular” doses has shown to be effective in improving survival even after 7-10 years after a first cardiovascular (CV) event in patients with coronary or ….