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Purpose of Review <p>High-density lipoprotein (HDL) is integral to reverse cholesterol transport (RCT), a process considered to protect against atherosclerotic cardiovascular disease (ASCVD). We summarise findings from the recent AEGIS-II trial and discuss new opportunities for HDL therapeutics targeted at RCT.</p> Recent Findings <p>Mendelian randomisation studies have suggested a causal association between the functional properties of HDL and ASCVD. However, the AEGIS-II trial of CSL112, an apolipoprotein A-I therapy that enhances cholesterol efflux, did not meet its primary endpoint. Exploratory analyses demonstrated that CSL112 significantly reduced ASCVD events among participants with a baseline low-density lipoprotein (LDL)-cholesterol ≥ 100&#xa0;mg/dL, suggesting that RCT may depend on LDL-cholesterol levels.</p> Summary <p>The role of HDL therapeutics in patients with familial hypercholesterolaemia, inherited low HDL-cholesterol and impaired HDL function, especially with inadequately controlled LDL-cholesterol, merits further investigation. The treatment of patients with monogenic defects in HDL metabolism remains a significant gap in care that needs further research.</p>

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Quo Vadis after AEGIS: New Opportunities for Therapies Targeted at Reverse Cholesterol Transport?

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年2月26日

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  • Nick S. R. Lan,
  • Gerald F. Watts

摘要

Purpose of Review

High-density lipoprotein (HDL) is integral to reverse cholesterol transport (RCT), a process considered to protect against atherosclerotic cardiovascular disease (ASCVD). We summarise findings from the recent AEGIS-II trial and discuss new opportunities for HDL therapeutics targeted at RCT.

Recent Findings

Mendelian randomisation studies have suggested a causal association between the functional properties of HDL and ASCVD. However, the AEGIS-II trial of CSL112, an apolipoprotein A-I therapy that enhances cholesterol efflux, did not meet its primary endpoint. Exploratory analyses demonstrated that CSL112 significantly reduced ASCVD events among participants with a baseline low-density lipoprotein (LDL)-cholesterol ≥ 100 mg/dL, suggesting that RCT may depend on LDL-cholesterol levels.

Summary

The role of HDL therapeutics in patients with familial hypercholesterolaemia, inherited low HDL-cholesterol and impaired HDL function, especially with inadequately controlled LDL-cholesterol, merits further investigation. The treatment of patients with monogenic defects in HDL metabolism remains a significant gap in care that needs further research.