PCSK9 inhibitors effectively lower LDL-C and reduce ASCVD risk, especially in statin-intolerant and familial hypercholesterolemia patients, with emerging therapies advancing treatment.
This review summarizes the current evidence for approved PCSK9 inhibitors and discusses novel therapies in development for the management of hypercholesterolaemia.
Cardiovascular disease remains the leading cause of death worldwide with low density lipoprotein being a major, yet modifiable, risk factor. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a central role in regulating low density lipoprotein (LDL) receptor expression. Naturally occurring loss-of-function variants in the PCSK9 gene result in lifelong lower LDL cholesterol (LDL-C) levels and significantly lower risk of atherosclerotic cardiovascular disease (ASCVD), providing strong genetic validation of PCSK9 as a therapeutic target. This insight has driven the development of therapies directed at PCSK9 for the management of hypercholesterolaemia, particularly in patients who fail to meet LDL-C targets despite maximally tolerated statin and ezetimibe. This is especially the case for patients who are statin intolerant or who have homozygous or heterozygous familial hypercholesterolaemia. The field has progressed rapidly from monoclonal antibodies to small interfering RNA and oral therapies, with gene editing strategies offering a potentially permanent inhibition of PCSK9. This review summarizes the evidence supporting the currently approved PCSK9 inhibitors. We discuss some novel therapies that are currently in development and consider some expanding indications for PCSK9 inhibition.
Mansfield et al. (2026) studied this question. PCSK9 inhibitors effectively lower LDL-C and reduce ASCVD risk, especially in statin-intolerant and familial hypercholesterolemia patients, with emerging therapies advancing treatment.
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