Advances in Non-statin Lipid Therapies: A Narrative Review of Evolving Strategies for Cardiovascular Risk Reduction

Area of Science:

• Cardiology
• Pharmacology
• Genetics

Background:

• Statin therapy is beneficial for atherosclerotic cardiovascular disease (ASCVD) risk reduction.
• Many patients do not achieve target low-density lipoprotein cholesterol (LDL-C) levels or experience statin intolerance.
• Alternative lipid-lowering strategies are crucial for managing residual ASCVD risk.

Purpose of the Study:

• To review current and emerging non-statin lipid-lowering therapies.
• To evaluate their efficacy, safety, and mechanisms of action.
• To propose a framework for personalized lipid management and discuss implementation barriers.

Main Methods:

• Review of landmark clinical trials for non-statin lipid-lowering medications.
• Analysis of mechanisms of action, clinical efficacy, and safety profiles.
• Exploration of emerging therapies and implementation challenges.

Main Results:

• Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (monoclonal antibodies, inclisiran) and bempedoic acid demonstrate significant LDL-C reduction.
• Emerging therapies target novel pathways like lipoprotein(a), apolipoprotein C-III, ANGPTL3, CETP, and utilize gene editing.
• Personalized management frameworks and clinical decision pathways are proposed.

Conclusions:

• Non-statin therapies provide vital options for patients with statin intolerance or suboptimal LDL-C control.
• Personalized approaches are needed to address residual risk and complex patient profiles.
• Overcoming cost and access barriers is essential for global implementation of advanced lipid-lowering strategies.