Hypercholesterolemia and cardiovascular disease: the dilemma of effective treatment for target achievement according to guidelines and national healthcare policies and a call to action.

The burden of cardiovascular disease (CVD) remains a worldwide challenge. CVDs, in particular atherosclerotic CVD, are still an important cause of mortality and morbidity. The increase in life expectancy is a further determining factor in the epidemiology of CVDs in some countries, such as Italy, which increases the urgency of intervening on modifiable risk factors. Among these, hypercholesterolemia is present in a significant percentage of CVD patients. A linear relationship between the risk of acute events and the plasma level of low-density lipoproteins cholesterol (LDL-C) is well known. The reduction of LDL-C levels leads to a decrease in mortality and morbidity. The overall recommendation is to treat hypercholesterolemia intensively and as early as possible. Statins, ezetimibe, bempedoic acid, pro-protein convertase subtilisin/kexin 9 inhibitors (i.e., the monoclonal antibodies alirocumab and evolocumab, or the small interfering RNA inclisiran) are all available for reaching LDL-C targets according to risk profile. While the real-world data confirm the safety of currently recommended LDL-C targets, data on their actual achievement are discouraging, less than half of patients on therapy reach the LDL-C targets recommended by the most recent ESC/EAS Guidelines. The causes of this critical discrepancy are multiple, arising from the various components that characterize the complex relationship between patient and physician within the healthcare system. A call to action is needed. Doctors should be continuously updated on the latest evidence, follow recommendations and engage the patient in the therapeutic process. Regular monitoring of the effects of the prescribed therapy, also through e-health and telemedicine tools, is essential, as well as changing therapy when LDL-C is not adequately controlled. Finally, health systems should align with guidelines and promote good clinical practices, overcoming a silo system, to impact outcomes in terms of overall sustainability.