Cardiovascular disease (CVD) is the most common cause of morbidity and mortality w in Switzerland. Several clinical trials have demonstrated that therapies reducing lipoprotein cholesterol (LDL-C) levels were beneficial in terms of major adverse cardiovascular events (MACE) risk reduction. Most of the evidence derived from statin therapy, and in patients with already established CVD, whereas the evidence remains weaker in primary prevention. Non-statin therapies have also been tested on top of statin to evaluate if additional lowering of LDL-C levels could influence clinical outcomes. Two therapies ezetimibe and proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors have shown positive results in patients with already established CVD. For this reason, the 2019 European Society of Cardiology (ESC) guidelines recommend in very-high risk patients both a reduction of LDL-C of ≥50% and an LDL-C target of < 55 mg/dL (<1.4 mmol/l) and the combination of statin with non-statin therapies to reach those targets.

The work presented in this thesis explored key aspects of lipid-lowering therapies in patients with acute coronary syndromes (ACS), a very-high risk group of patients. We first investigated the impact of a hospital-based secondary prevention on outcomes, then the reasons for therapies discontinuation and how the achievement of LDL-C targets and eligibility for novel treatment can depend on the guidelines definition. We also studied the benefice of early and intensive lowering LDL-C in patients with a recent myocardial infarction and discussed whether novel aggressive therapies should be implemented or not at the time of ACS hospitalization. We then summarized the evidence of LDL-C lowering in the elderly, which was a neglected subgroup so far in most of the trials and observed that reaching very low LDL-C levels was safe for cognition. Pursuing the safety of lipid-lowering therapies, we summarized the evidence regarding the risk of atrial fibrillation events observed in trials testing marine omega-3 supplementation, which is widely used to lower triglycerides levels. Since risk prediction and individualization of therapies are key aspects of management, we investigated the prognosis role of novel biomarkers, such as PCSK9, trimethylamine N-oxide (TMAO), ceramides and testosterone levels. Finally, we also studied lifestyle interventions to help smokers to quit smoking and planned an ongoing trial on the safety of moderate alcohol consumption after a recent myocardial compared to abstinence.