Targeting APOC3 with Olezarsen in Moderate Hypertriglyceridemia

To the Editor: The ESSENCE-TIMI (Thrombolysis in Myocardial Infarction) 73b trial by Bergmark and colleagues (Oct. 2 issue), 1 which evaluated olezarsen in patients with moderate hypertriglyceridemia, represents an important advance in hypertriglyceridemia treatment. However, by inhibiting hepatic triglyceride production through suppression of apolipoprotein C-III, olezarsen may paradoxically impair hepatocellular fatty acid handling. Triglyceride formation serves as a protective mechanism to buffer excess free fatty acids by sequestering them into inert lipid droplets. Interfering with this pathway could therefore increase hepatic lipotoxic stress, inflammation, and hepatocellular injury. In the trial, mild but significant elevations in aminotransferase levels were reported among recipients . . .