Over the past few decades, the number of deaths from cardiovascular disease has declined substantially in developed countries. Statins, drugs that lower serum levels of low-density lipoprotein cholesterol (LDL-C), have been instrumental in this trend. Not everyone responds to statins, however, and new types of cholesterol-lowering drugs are attracting great interest. Fitzgerald et al. tested inclisiran, a drug based on small interfering RNA technology, in a small phase 1 trial. Inclisiran induces degradation of the mRNA encoding PCSK9, a liver-derived protease whose activity increases serum LDL-C levels. Subcutaneous injection of inclisiran durably reduced PCSK9 levels by as much as 83% and LDL-C levels by as much as 59% without serious toxicities.
