Olezarsen for the treatment of hypertriglyceridemia: A Bayesian reanalysis of randomized controlled trials

Hypertriglyceridemia is associated with an increased risk of atherosclerotic cardiovascular (CV) disease. Olezarsen, an apolipoprotein C-III (APOC3) inhibitor, lowers triglyceride (TG) levels. Using a Bayesian reanalysis that incorporated prior evidence, we estimated the effects of olezarsen on TG and apolipoprotein B levels in patients with severe or moderate hypertriglyceridemia who were at high CV risk. We searched PubMed, Embase, and Cochrane data bases for randomized clinical trials comparing treatment with olezarsen versus placebo in patients with severe or moderate hypertriglyceridemia who were at CV risk. Mean differences (MDs) and 95% credible intervals (CrIs) were pooled with a Bayesian random-effects model using a vague prior for the overall effect and between-study heterogeneity. We included 4 randomized clinical trials with a total of 2678 patients, of whom 1930 (72%) received olezarsen. Most participants were men (67%) with a mean age of 60 years and a follow-up of 12 months. The baseline median TG level was 468 mg/dL (range, 239.9-838 mg/dL), and 941 (35%) patients had a history of atherosclerotic CV disease. Olezarsen was associated with reductions from baseline in TG (MD, -57.77%; 95% CrI, -66.76 to -48.45), APOC3 (MD, -66.97%; 95% CrI, -77.67 to -55.30), and apolipoprotein B (MD, -12.78%; 95% CrI, -26.76 to -0.10), as well as an increase in low-density lipoprotein cholesterol levels (MD, 25.89%; 95% CrI, 5.76-46.51) compared with placebo. In this Bayesian meta-analysis involving patients with severe hypertriglyceridemia and high CV risk, olezarsen was effective in reducing TG, APOC3, and apolipoprotein B levels. SIGNIFICANCE STATEMENT: In this Bayesian meta-analysis of randomized trials, olezarsen markedly reduced triglycerides, apolipoprotein C-III, apolipoprotein B, and non-high-density lipoprotein levels in patients with severe or moderate hypertriglyceridemia who were at high cardiovascular risk. These findings are limited to surrogate lipid biomarkers, and whether these improvements translate into reductions in cardiovascular events remains unknown.