PCSK9 inhibitors (PCSK9i), a new opportunity for cardiovascular prevention: Clinical and regulatory aspects and access to therapy

Elevated levels of LDL-C represent a major risk factor for cardiovascular (CV) disease and recent guidelines recommended early and appropriate interventions in hypercholesterolemic patients in order to reduce the risk of CV events. The current lipid lowering therapies (mainly statins and ezetimibe) not always allow patients to reach their appropriate LDL-C goals. This is particularly true in patients affected by genetic forms of hypercholesterolemia as well as in those who need to attain low LDL-C due to their high cardiovascular risk. In this context, the recent availability of monoclonal antibodies directed against the PCSK9 protein (PCSK9i) represent a novel therapeutic strategy to control resistant forms of hypercholesterolemia. In this review, we will examine the clinical pharmacology of PCSK9i and we will dedicated particular attention to review the results of the two pivotal cardiovascular prevention trials, FOURIER and ODISSEY OUTCOMES that demonstrated the benefit of PCSK9i in prevention of cardiovascular events in patients at very high risk not at LDL-C goal with conventional LDL-lowering therapies. The PCSK9i has been approved for use in Italy under specific criteria and following a strict prescription procedures. We will examine the epidemiology of use of PCSK9i in Italy and will underlying the potential factors influencing the access and availability to this therapy.