Elevated low-density lipoprotein cholesterol (LDL-C) plays a major role in the development of atherosclerotic cardiovascular disease. Statins are the first-line treatment to lower LDL-C in patients with hypercholesterolemia; however, some high cardiovascular risk patients may have inadequate responses to statin therapy or are intolerant to statins, and may need additional and/or alternative non-statin therapies to further reduce their LDL-C levels. Monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of circulating LDL-C levels, have received considerable attention as promising non-statin therapeutic options for the management of hypercholesterolemia. This review provides a brief overview of the history and science of PCSK9 inhibitors, focusing on two PCSK9 monoclonal antibodies that have been approved by the US Food and Drug Administration: alirocumab and evolocumab. Recently released and forthcoming clinical trial data will be discussed, as well as the practical application of patient populations that may benefit from PCSK9 inhibitors. Finally, the recent expert recommendations regarding the use of PCSK9 inhibitors and other non-statin therapies to treat patients with inadequate LDL-C-lowering on statin therapy will be summarized.
Keywords: Alirocumab; LDL-C; PCSK9 inhibitors; evolocumab; statin.