HDL therapy: the next big step in the treatment of atherosclerosis?

Abstract

Despite significant reductions in mortality with statins and increasingly lower targets of low-density-lipoprotein cholesterol, two thirds of cardiovascular events cannot be prevented with current treatments. Therefore, a clear need for additional therapeutic interventions to complement the results of low-density lipoprotien lowering, exists. One prime target for new interventions is high-density lipoprotein (HDL) and/or its apolipoproteins. While lifestyle interventions and well-established drugs, such as fibrates and nicotinic acid, modestly increase HDL, the most promising current approaches are direct infusion of HDL-like particles (e.g., apolipoprotein AI Milano–phospholipid complexes) and inhibition of one of the key enzymes in HDL metabolism, cholesterol ester transfer protein. These methods have been shown to have dramatic effects on the incidence of atherosclerosis and/or HDL cholesterol. This review will focus on treatments that raise HDL cholesterol or enhance reverse cholesterol transport. Old and new drugs will be discussed as well as combination therapy and novel approaches such as plasma delipidation and recombinant apolipoprotein AI.