Inclisiran-will it fulfill its promise?

Elevated low-density lipoprotein cholesterol (LDL-C) is a well-established, independent risk factor for atherosclerotic cardiovascular disease (ASCVD), with absolute LDL-C reduction translating into proportional reductions in ASCVD events. Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as an effective lipid-lowering strategy. This review summarizes current evidence on the efficacy and safety of inclisiran, a small interfering RNA (siRNA) therapy that inhibits hepatic PCSK9 synthesis, in primary and secondary ASCVD prevention, as well as in heterozygous familial hypercholesterolaemia (HeFH) and homozygous familial hypercholesterolaemia (HoFH).

Randomized clinical trials have demonstrated that inclisiran produces robust and sustained reductions in LDL-C and circulating PCSK9 levels across a broad spectrum of patients, including those with established ASCVD, ASCVD risk equivalents, and FH. Its twice-yearly dosing regimen may substantially improve long-term treatment adherence. Long-term data (up to 6 years) indicate a favorable safety and tolerability profile, with no dose adjustments required in patients with renal or hepatic impairment. Ongoing randomized outcome trials are expected to clarify the impact of inclisiran on ASCVD events.

Current evidence supports its role as a promising adjunct or alternative to established lipid-lowering therapies, including statins, particularly in patients requiring additional LDL-C reduction.