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

In Reply We appreciate Guijarro’s interest in our article.¹ We agree with Guijarro that there are important differences in the mechanism of action between statins and proprotein convertase subtilisin/kexin type 9 inhibitors. Evolocumab has now demonstrated a favorable safety and tolerability profile during extended long-term open-label observation (the OSLER trial¹) and in a large randomized, placebo-controlled clinical trial (the FOURIER trial²). Importantly, in the FOURIER trial, the safety analyses compared evolocumab with placebo, not lower vs higher levels of LDL, and found no safety imbalances other than a slight increase in injection site reactions in the evolocumab group.² We would also add that extensive randomized clinical trial data show that statins are a safe therapeutic class.