Current and Emerging Treatment Options for Hypertriglyceridemia: State-of-the-Art Review

Area of Science:

• Cardiovascular Medicine
• Pharmacology
• Metabolic Disorders

Background:

• Hypertriglyceridemia (HTG) is linked to increased atherosclerotic cardiovascular disease risk.
• Severe elevations in triglycerides (TG), especially in familial chylomicronemia syndrome (FCS), can cause acute pancreatitis.
• Existing therapies like statins and fibrates may not sufficiently lower TG levels.

Purpose of the Study:

• To review pharmacological targets in triglyceride-rich lipoprotein metabolism.
• To discuss current international guidelines for HTG management.
• To summarize recent clinical trial evidence on emerging HTG treatments.

Main Methods:

• Comprehensive literature review of pharmacological targets.
• Analysis of international clinical practice guidelines.
• Synthesis of data from recent clinical trials on novel HTG therapies.

Main Results:

• Novel antisense oligonucleotides and small interfering ribonucleic acids target key modulators of TG metabolism.
• Apolipoprotein C-III (apoC-III) inhibitors (olezarsen, plozasiran) show promise with improved safety profiles.
• Angiopoietin-like protein 3 (ANGPTL3) inhibitors (zodasiran) and FGF21 analogs (pegozafermin) are emerging candidates for HTG treatment.

Conclusions:

• Emerging therapies targeting TG-rich lipoprotein metabolism offer new treatment avenues for HTG.
• These novel agents, including apoC-III and ANGPTL3 inhibitors, and FGF21 analogs, present potential alternatives to standard treatments.
• Further research and clinical trials are crucial to establish the efficacy and safety of these novel therapies in managing HTG and its complications.