The class
Review argues HDL-raising therapy remains an unmet cardiovascular need after torcetrapib and dalcetrapib failures (Transl Med UniSa 2015)
Original title: High Density Lipoprotein Cholesterol Increasing Therapy: The Unmet Cardiovascular Need
Despite aggressive LDL-lowering strategies, cardiovascular risk remains substantial in coronary artery disease patients, prompting continued interest in HDL-raising therapy. This review discusses how the dramatic failure of clinical trials testing the CETP inhibitors torcetrapib and dalcetrapib cast considerable doubt on raising HDL cholesterol as a cardiovascular strategy, and how these results, together with animal studies, revealed the importance of HDL functional quality over circulating quantity. The authors argue that HDL-based interventions preserving or enhancing HDL functionality, particularly reverse cholesterol transport, deserve closer investigation, and review HDL metabolism, available clinical-trial data for HDL-raising agents, and potential future HDL-based therapeutic strategies.
Original abstract
Despite aggressive strategies are now available to reduce LDL-cholesterol, the risk of cardiovascular events in patients with coronary artery disease remains substantial. Several preclinical and clinical studies have shown that drug therapy ultimately leads to a regression of the angiographic lesions but also results in a reduction in cardiovascular events. The dramatic failure of clinical trials evaluating the cholesterol ester transfer protein (CEPT) inhibitors, torcetrapib and dalcetrapib, has led to considerable doubt about the value of the current strategy to raise high-density lipoprotein cholesterol (HDL-C) as a treatment for cardiovascular disease. These clinical results, as well as animal studies, have revealed the complexity of HDL metabolism, assessing a more important role of functional quality compared to circulating quantity of HDL. As a result, HDL-based therapeutic interventions that maintain or enhance HDL functionality, such as improving its main property, the reverse cholesterol transport, require closer investigation. In this review, we will discuss HDL metabolism and function, clinical-trial data available for HDL-raising agents, and potential strategies for future HDL-based therapies.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.