AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Real-World Eligibility for ApoC-III Inhibitor Therapy Among U.S. Adults with Severe Hypertriglyceridemia: A National Population-Based Analysis
By Kushmeliuk S, Prakash Y, Midha M et al.
Background: ApoC-III inhibitors (ApoC3i), including olezarsen and plozasiran, are currently only FDA-approved for familial chylomicronemia syndrome (FCS). Recent phase 3 trials have demonstrated substantial triglyceride (TG) reduction in patients with severe hypertriglyceridemia (sHTG) with resulting reduction in acute pancreatitis events. The impact of expanded ApoC3i indications on treatment eligibility in the populations remains unknown. Research Question: This study aimed to assess how many patients would have new ApoC3i eligibility based on recent trial data and further model the effect of glucagon-like peptide-1 receptor agonists (GLP1) eligibility on ApoC3i eligibility. Methods: We conducted a cross-sectional analysis of 11,153 adults from NHANES 2011-2020, representing ~258 million U.S. adults. ApoC3i eligibility for sHTG was defined using trial-based criteria: CORE/CORE2 (TG ≥500 mg/dL + LLT). GLP1 eligibility was assessed per FDA-approved indications. Sensitivity analyses modeled 15%, 20%, and 25% GLP1-mediated TG reductions to estimate retention of ApoC3i eligibility. Analyses incorporated complex survey weights and linearization-based variance estimation. Results: Severe HTG (TG ≥500 mg/dL) affected 0.63% of U.S. adults (~1.63 million), while higher-risk HTG (TG ≥880 mg/dL) affected ~360,000 adults. Approximately 520,000 met CORE/CORE2 criteria requiring background LLT, indicating that 68.0% of adults with severe HTG were untreated. About 78,000 met potential chylomicronemia criteria defined as TG ≥ 880 mg/dL, indicating that 78.3% of adults with higher-risk HTG receive no LLT. Under moderate TG reduction assumptions (20%), GLP1 therapy would reduce 50.8% of sHTG patients below TG 500 mg/dL, while 36.3% remained dual-eligible for GLP1 and ApoC3i therapy. Conclusion: Expanding ApoC3i indications beyond FCS could increase eligibility to ~520,000 adults. With higher baseline LLT utilization, an even higher amount would be eligible for ApoC3i therapy. Despite potential displacement by GLP1-mediated TG reduction, a significant proportion of U.S. adults with sHTG would remain eligible for ApoC3i therapy under expanded indications.