PCSK9 inhibitors: when statins aren't enough

Abstract

The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, evolocumab and alirocumab, are novel lipid‐lowering agents that can produce a further substantial reduction in LDL cholesterol in patients who cannot reach target using standard therapy with statins and ezetimibe. This article examines the current approaches to lipid‐lowering for primary and secondary prevention of cardiovascular disease and the place of these new agents in therapy.

Can LDL cholesterol ever be lowered too much?

“…In addition to whatever may be achieved by lifestyle change and statins, any future adherence to a 'lower is better' clinical approach to LDL cholesterol control (especially in those patients at highest cardiovascular risk) will likely require a much greater role for add-on or alternative therapies that can further upregulate hepatic LDL receptors. 7,9,26,35 Interestingly in this regard, a recent change to the marketing authorisation for the PCSK9 inhibitor evolocumab means that it is now also licensed in adults with established atherosclerotic cardiovascular disease to reduce cardiovascular risk (as add-on therapy to a maximum tolerated dose of a statin). 36 However, NICE is yet to appraise its use for this indication.…”

“…But a new breed of LDL cholesterol-lowering agents, the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (represented by alirocumab and evolocumab), has now disrupted this status quo by providing a non-statin therapeutic option that rivals LDL cholesterol lowering by statins. [7][8][9] Can LDL cholesterol ever be lowered too much?…”