Statins Alone or in Combination with Ezetimibe or PCSK9 Inhibitors in Atherosclerotic Cardiovascular Disease Protection

Statins have proved to be very effective in reducing atherosclerotic cardiovascular disease (ASCVD) risk, with no apparent threshold at which low-density lipoprotein cholesterol (LDL-C) lowering is not associated with a reduced risk. Yet, several meta-analyses of statin trials show significant on-treatment residual risk of major cardiovascular (CV) events. This finding points to the unmet needs, in terms of LDL-C targets and ASCVD protection, of statin-treated patients, raising the question of statin combination therapy. Ezetimibe is a cholesterol absorption inhibitor, with the potency to decrease LDL-C for about 10–18%, apolipoprotein B (apoB) for 11–16%, while, in combination therapy with statins, leads to an additional LDL-C lowering of 25%, with a total LDL-C lowering of 34–61%. It is also estimated that 10–20% of patients on statin treatment cannot tolerate them. As a result, adequate doses to achieve treatment target, or as recommended for the patient-specific risk profile, cannot be prescribed. Proprotein convertase subtilisin/kexin type 9 (PCSK9) Inhibitors are monoclonal antibodies that inhibit the binding of PCSK9 to LDL-C receptors. Besides a very potent lipid-lowering effect, PCSK9 inhibitors have added ASCVD risk reduction benefit due to a very aggressive LDL-C lowering action, especially beneficial in patients who are intolerant to statins.