Trial of the Oral PCSK9 Inhibitor Enlicitide

To the Editor: The CORALreef Lipids trial, conducted by Navar et al. (Feb. 5 issue), 1 showed a marked reduction from baseline in the low-density lipoprotein (LDL) cholesterol level with the oral proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitor enlicitide, as compared with placebo. We would like to note some limitations that warrant attention. First, the trial evaluated only surrogate lipid end points without evaluating cardiovascular end points, 2 and the 52-week follow-up cannot confirm the long-term efficacy of treatment, durability of effect, or potential resistance to the drug, which may occur with compensatory PCSK9 up-regulation. The answers to these questions will . . .