HDL as a treatment target: a review says the obicetrapib outcomes trial will help decide whether to abandon the HDL hypothesis for good (Curr Atheroscler Rep 2023)

Original title: HDL as a Treatment Target: Should We Abandon This Idea?

Curr Atheroscler Rep · 1 December 2023 · 6

Begue F, Apalama ML, Lambert G, Meilhac O

A review questioning whether HDL cholesterol should remain a cardiovascular treatment target, noting that neither HDL-raising drugs nor infusions of reconstituted HDL have convincingly proven beneficial for cardiovascular health despite the established anti-inflammatory, antioxidant and reverse-cholesterol-transport properties of HDL. The authors identify two pending large trials as decisive: one testing the latest CETP inhibitor, obicetrapib, the other testing reconstituted HDL infusion after acute coronary events. If both prove negative, the authors argue this would seal the fate of HDL as a direct cardiovascular therapeutic target, though they note HDL-directed therapy could still hold promise outside the cardiovascular field if its beneficial properties can be better optimised. Written before the obicetrapib phase 3 results were available.

Original abstract

Purpose Of Review: High-density lipoproteins (HDL) have long been regarded as an antiatherogenic lipoprotein species by virtue of their role in reverse cholesterol transport (RCT), as well as their established anti-inflammatory and antioxidant properties. For decades, HDL have been an extremely appealing therapeutic target to combat atherosclerotic cardiovascular diseases (ASCVD).

Recent Findings: Unfortunately, neither increasing HDL with drugs nor direct infusions of reconstituted HDL have convincedly proven to be positive strategies for cardiovascular health, raising the question of whether we should abandon the idea of considering HDL as a treatment target. The results of two large clinical trials, one testing the latest CETP inhibitor Obicetrapib and the other testing the infusion of patients post-acute coronary events with reconstituted HDL, are still awaited. If they prove negative, these trials will seal the fate of HDL as a direct therapeutic target. However, using HDL as a therapeutic agent still holds promise if we manage to optimize their beneficial properties for not only ASCVD but also outside the cardiovascular field.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.