Expert Insights: Recommendations on FH, Triglycerides in 2026 Dyslipidemia Guidelines

The 2026 ACC/AHA Dyslipidemia Guideline provides its most granular guidance yet for patients with familial hypercholesterolemia (FH) and severe hypertriglyceridemia, with new genetic testing recommendations, a novel therapy for homozygous FH, and the first extensive management framework for triglyceride-related risk across the full severity spectrum.

Writing committee members Pamela B. Morris, MD, and Ann Marie Navar, MD, PhD, walk through four distinct patient groups defined by LDL elevation and FH status. For patients with LDL cholesterol above 190 mg/dL without meeting clinical or genetic FH criteria, the LDL goal is less than 100 mg/dL, with combination therapy recommended when statins alone are insufficient.

Heterozygous FH carries a more aggressive target of less than 70 mg/dL, reflecting the cumulative cardiovascular risk conferred by years of elevated LDL exposure. In patients with heterozygous FH and established ASCVD, the goal tightens further to less than 55 mg/dL. For homozygous FH, a rare but severe condition in which minimal to absent LDL receptor function renders most conventional therapies substantially less effective, the guideline introduces evinacumab, an ANGPTL3 inhibitor lowering LDL through a mechanism entirely independent of LDL receptor upregulation.

Both evinacumab and lomitapide receive Class IIb recommendations in this population. Genetic testing for FH is now formally recommended, as monogenic variants can be identified in patients with LDL levels below the 190 mg/dL threshold, and genetic confirmation facilitates cascade screening among at-risk family members.

In hypertriglyceridemia, the guideline, reflecting its renamed scope as a dyslipidemia rather than blood cholesterol document, establishes ASCVD risk, not pancreatitis, is the primary concern for most patients with triglycerides below 500 mg/dL, reinforcing statin therapy as foundational in this group. Above 500–1000 mg/dL, fibrates and high-dose prescription omega-3 fatty acids are appropriate adjuncts.

For patients with familial chylomicronemia syndrome (FCS), a rare condition marked by severe triglyceride elevation and recurrent pancreatitis resistant to standard lipid-lowering therapy, olezarsen, an APOC3 inhibitor, is now recommended. Plozasiran, approved after the guideline's evidence review concluded, represents an additional emerging option. Morris and Navar also recommend referral to a registered dietitian for patients at risk of pancreatitis, given the complexity of dietary management in severe hypertriglyceridemia.

Morris has no relevant disclosures to report. Navar reports disclosures with Amge, Arrowhead Pharmaceuticals, AstraZeneca, Bayer, Eli Lilly and Company, Esperion, Johnson & Johnson, Merck, Miga Health, NewAmsterdam Pharma, Novartis, Novo Nordisk, Sanofi, and Silence Therapeutics, among others.

References:

1. Blumenthal RS, Morris PB, Gaudino M, et al. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. Published online March 13, 2026. doi:10.1016/j.jacc.2025.11.016
2. American College of Cardiology. ACC/AHA Issue Updated Guideline for Managing Lipids, Cholesterol - American College of Cardiology. American College of Cardiology. Published March 13, 2026. Accessed March 23, 2026. https://www.acc.org/About-ACC/Press-Releases/2026/03/13/18/01/ACCAHA-Issue-Updated-Guideline-for-Managing-Lipids-Cholesterol