Lipid-Lowering RNA Therapeutics for Atherosclerotic Cardiovascular Disease Prevention: A State-of-the-Art Review

Area of Science:

• Cardiovascular Medicine
• Pharmacology
• Genetics

Background:

• Despite current lipid-lowering therapies, many patients with atherosclerotic cardiovascular disease (ASCVD) do not achieve recommended lipid goals.
• Residual risk for ASCVD events remains a significant clinical challenge.
• Ribonucleic acid (RNA)-based therapeutics have emerged as a promising new class of agents.

Purpose of the Study:

• To review the clinical development of novel RNA-based therapeutics for lipid lowering.
• To examine the efficacy and safety of these agents in managing hyperlipidemia.
• To identify challenges for future clinical trials of RNA therapeutics in ASCVD prevention.

Main Methods:

• Literature review of ongoing clinical trials and published studies on RNA-based lipid-lowering agents.
• Analysis of efficacy and safety data for antisense oligonucleotides and small interfering RNA.
• Discussion of therapeutic targets including low-density lipoprotein, lipoprotein(a), and triglyceride-rich lipoproteins.

Main Results:

• RNA therapeutics, including antisense oligonucleotides and small interfering RNA, demonstrate potential in reducing specific lipoprotein levels.
• These agents target key pathways involved in lipoprotein metabolism and ASCVD risk.
• Early-phase clinical data suggest favorable efficacy and safety profiles for certain RNA-based therapies.

Conclusions:

• RNA-based therapeutics represent a significant advancement in managing refractory hyperlipidemia and mitigating residual ASCVD risk.
• Further clinical trials are necessary to establish the long-term efficacy and safety of these novel agents.
• RNA therapeutics hold promise as a future strategy for ASCVD prevention in high-risk patient populations.