Synthetic HDL as a new treatment for atherosclerosis regression: has the time come?

Plasma high-density lipoprotein cholesterol (HDL-C) has received considerable attention as a potential therapeutic target to further reduce cardiovascular events in the statin era. One therapeutic approach to enhance HDL-mediated atheroprotection involves the use of small, synthetic and orally-active compounds that substantially raise plasma HDL-C levels. However, doubts on the clinical benefit achievable with such treatments have been raised by the premature termination of a large Phase III trial with torcetrapib, the most potent and furthest developed HDL-C raising compound, because of excess mortality in patients receiving the drug. The alternative is the direct administration of synthetic HDL (sHDL), discoidal lipoprotein particles which mimic most, if not all, of the atheroprotective properties of plasma HDL. Short-term treatments with sHDL of different composition caused consistent and remarkable reductions of atheroma volume in patients with acute coronary syndromes (ACS). Although at early stages of drug development, sHDL hold vast promise for plaque stabilization/regression, and cardiovascular event reduction.