Treatment of Hypertriglyceridemia: A Review of Therapies in the Pipeline

Background The 2018 American College of Cardiology/American Heart Association (ACC/AHA) guidelines and 2021 ACC Expert Consensus Decision Pathway recommend nonpharmacological interventions and initiation of statin therapy for patients with moderate hypertriglyceridemia and addition of fibrates or omega-3 fatty acids in severe hypertriglyceridemia. Although the association between triglyceride (TG) lowering and atherosclerotic cardiovascular disease (ASCVD) risk reduction remains controversial, patients with hypertriglyceridemia may represent a subgroup that require additional therapy to further reduce residual ASCVD risk. Moreover, medications that target novel pathways could provide alternative options for patients who are intolerant of existing therapies or doses needed to provide adequate triglyceride lowering. Objective: Assess recent evidence for TG-lowering agents including omega-3 fatty acid-based therapies, PPARα modulators, apoC-III mRNA antisense inhibitors, angiopoietin-like 3 (ANGPTL3) antibodies, and herbal supplements. Methods: A literature search was performed using PubMed with hypertriglyceridemia specified as a MeSH term or included in the title or abstract of the article along with each individual agent. For inclusion, trials needed to have a primary or secondary outcome of TG levels or TG lowering. Conclusion: Currently, the only US Food and Drug Administration approved medication for CV risk reduction in patients with hypertriglyceridemia is icosapent ethyl. Results from phase 3 trials for CaPre, pemafibrate, and volanesorsen as well as additional evidence for pipeline pharmacotherapies with novel mechanisms of action (e.g., ApoC-III mRNA antisense inhibitors and ANGPTL3 antibodies) will help to guide future pharmacotherapy considerations for patients with hypertriglyceridemia.