The Indonesian Biomedical Journal
Vol 18, No 2 (2026)

The Role of PCSK9 Inhibition and Small Interference RNA (siRNA) in The Management of Dyslipidaemia and ASCVD

Santoso, Anwar (Unknown)
Dwiputra, Bambang (Unknown)



Article Info

Publish Date
29 Apr 2026

Abstract

Compelling evidence linking low-density lipoprotein cholesterol (LDL-C) reduction to decreased mortality has positioned LDL-C lowering as a central strategy in the prevention of atherosclerotic cardiovascular disease (ASCVD). Nonetheless, despite widespread statin use, an estimated 10–20% of individuals at high or very high cardiovascular risk fail to attain guideline-recommended LDL-C targets. This persistent treatment gap underscores the need for more potent and durable lipid-lowering strategies, particularly among patients with familial hypercholesterolemia (FH) and those with established ASCVD whose LDL-C levels remain inadequately controlled despite optimized combination therapy, including statins, ezetimibe, and proprotein convertase subtilisin–kexin type 9 (PCSK9) monoclonal antibodies. Inclisiran, a first-in-class small interfering RNA agent, addresses this unmet need by selectively inhibiting hepatic synthesis of PCSK9, thereby enhancing low-density lipoprotein receptor (LDLR) recycling and accelerating LDL-C clearance. Nevertheless, thus far, no cardiovascular outcome trial (CVOT) has been available. With a convenient twice-yearly dosing regimen, inclisiran consistently achieves LDL-C reductions exceeding 50% and demonstrates a favourable tolerability profile, offering an effective and patient-friendly advancement in dyslipidaemia management.KEYWORDS: dyslipidaemia, ASCVD, PCSK9 inhibition, siRNA, inclisiran 

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