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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.

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