PCSK9 Inhibitors, Statins, Low-Density Lipoprotein Cholesterol, Mevalonate Pathway, and Toxicity

To the Editor In a study by Koren et al,¹ proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors exhibited potent and persistent long-term efficacy in reducing low-density lipoprotein (LDL) cholesterol levels. In the 2017 FOURIER trial by Sabatine et al,² evolocumab demonstrated cardiovascular protection in the absence of significant toxic effects despite very low LDL cholesterol levels. However, the strong emphasis on very low circulating LDL cholesterol levels may be an inadequate focus for assessing the adverse effects of PCSK9 inhibitors.