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Review
. 2020 Aug;31(4):182-186.
doi: 10.1097/MOL.0000000000000691.

Small interfering RNA to proprotein convertase subtilisin/kexin type 9: transforming LDL-cholesterol-lowering strategies

Julia Brandts  1   2 , Kausik K Ray  2
Affiliations
Review

Small interfering RNA to proprotein convertase subtilisin/kexin type 9: transforming LDL-cholesterol-lowering strategies

Julia Brandts et al. Curr Opin Lipidol. 2020 Aug.

Abstract

Purpose of review: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is a new strategy to reduce LDL cholesterol (LDL-C), that is currently pursued by mAbs. A promising novel approach to target PCSK9 is using small interfering RNAs to inhibit hepatic PCSK9 synthesis. The first small interfering RNA developed for this purpose is inclisiran. Here, we review its clinical trial data and potential impact on patient management.

Recent findings: Inclisiran achieves sustained, additional 50% LDL-C reduction in patients receiving background statin therapy. Resulting LDL-C changes can be maintained by an infrequent dosing regimen with twice per year injections, that appear safe and well tolerated. Thus far, inclisiran has been studied in patients with established cardiovascular disease, high-risk primary prevention and in patients with familial hypercholesterolemia.

Summary: High and very high-risk individuals may benefit from the additional LDL-C-lowering effect of inclisiran when added to current lipid-lowering therapies. Furthermore, the simple dosing regimen may improve the convenience for users and facilitate patient adherence to therapy. The safety and convenience of inclisiran may offer new opportunities for population health.

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