Another brick in the wall of severe hypertriglyceridaemia lowering

This comment refers to ‘Olezarsen for Managing Severe Hypertriglyceridemia and Pancreatitis Risk’ which was published in the New England Journal of Medicine, https://doi.org/10.1056/NEJMoa2512761. The CORE-TIMI 72a and CORE2-TIMI 72b studies were two phase 3, multicentre, company-funded, double-blind, randomized controlled trials (RCTs) with identical design, aimed to evaluate the efficacy and safety of olezarsen—an antisense oligonucleotide (ASO) targeting apolipoprotein C-III (ApoC-III)—in patients with severe hypertriglyceridaemia, defined as a fasting triglyceride level of at least 500 mg per decilitre (mg/dL).1 The primary endpoint was the placebo-adjusted per cent change in fasting triglyceride levels at 6 months. Secondary endpoints included triglyceride changes at 12 months; changes in ApoC-III, remnant cholesterol, and non-HDL cholesterol at 6 and 12 months; the proportion of patients achieving triglyceride levels below prespecified thresholds at 12 months; acute pancreatitis events; and changes in hepatic fat fraction assessed in a magnetic resonance imaging (MRI) substudy. Exploratory outcomes included changes in HDL cholesterol, LDL cholesterol, apolipoprotein B, and major adverse cardiovascular events (a composite of death from cardiovascular causes, myocardial infarction, ischaemic stroke, or arterial revascularization). Safety assessments focused on liver and kidney function and platelet counts. A total of 1061 patients were included in the primary analysis (617 in the CORE-TIMI 72a and 444 in the CORE2-TIMI 72b trial) and randomized in a 1:1:1 ratio to receive olezarsen at a dose of 50 mg, olezarsen at a dose of 80 mg, or placebo monthly for a 12-month treatment period. The median age was 54 years, with 24% women and 88% White. Randomization was stratified according to the triglyceride level at baseline [≥880 mg/dL (43%) or