Dyslipidemia is one of the most important risk factors for cardiovascular 
disease. Insufficient reduction in LDL-C from existing therapies in patients at 
high risk of atherogenic cardiovascular disease is an unmet clinical need. 
Circulating PCSK9 causes hypercholesterolemia by reducing LDL receptors in 
hepatocytes. Areas covered: PCSK9 inhibition has emerged as a promising new 
therapeutic strategy to reduce LDL-C. Inclisiran, a novel, synthetic, siRNA 
molecule, inhibits PCSK9 synthesis in hepatocytes. Inclisiran targets 
intracellular PCSK9 synthesis specifically, resulting in a dose-dependent, 
long-term, significant reduction in LDL-C. Inclisiran has been well tolerated 
and safe, without severe adverse events so far. This review discusses current 
PCSK9 inhibitors and the results of phase I and II clinical trials of 
inclisiran. Expert opinion: Plasma PCSK9 enhances the degradation of LDL 
receptor, resulting in accumulation of LDL-C in the circulation. Current 
approaches with monoclonal antibodies sequester circulating PCSK9 but require 
frequent injections. Inclisiran inhibits translation of PCSK9 mRNA and thus 
switches off PCSK9 production and provides advantages over monoclonal antibodies 
with an infrequent dosing interval of twice a year to reduce LDL-C by over 50%. 
Ongoing studies will establish the long-term safety of inclisiran in patients 
with high cardiovascular risk and an elevated LDL-C.