Atherosclerosis Residual Lipid Risk-Overview of Existing and Future Pharmacotherapies

Area of Science:

• Cardiovascular Medicine
• Lipidology
• Pharmacology

Background:

• Patients with atherosclerotic disease face residual cardiovascular risk despite optimal treatment.
• Lipoprotein particles and their content significantly influence future cardiovascular events.
• Low-density lipoprotein cholesterol (LDL-c) is a confirmed causal factor in atherosclerosis development.

Purpose of the Study:

• To review current therapies targeting lipid biomarkers for atherosclerotic disease.
• To explore the mechanistic role of various lipoproteins in cardiovascular risk.
• To identify potential new therapeutic targets beyond LDL-c.

Main Methods:

• Review of clinical trial data and mechanistic studies on lipid-modifying therapies.
• Analysis of genetic studies, including mendelian randomization, on lipid metabolism.
• Assessment of emerging lipid biomarkers and their association with cardiovascular events.

Main Results:

• Statins, ezetimibe, PCSK9 inhibitors, and bempedoic acid confirm LDL-c's role.
• HDL-c-raising therapies and triglyceride-lowering agents (fibrates, EPA) have not consistently reduced cardiovascular risk.
• Emerging markers like lipoprotein (a) and cholesterol efflux capacity show potential for risk reduction.

Conclusions:

• Targeting LDL-c remains crucial, but residual risk persists.
• Triglycerides' role is complex, with ongoing research into new agents.
• Novel lipid biomarkers may offer additional benefits when combined with existing therapies.