New lipid therapies (#206)
High quality clinical trial evidence supports the use of interventions that modify lipoprotein metabolism. Therapies that reduce low-density lipoprotein (LDL) cholesterol, particularly statins, have the greatest weight of supporting evidence. The evidence supporting the use of drugs that change other aspects of the lipoprotein profile, such as triglyceride-rich lipoproteins and high density lipoprotein (HDL) cholesterol are less well established. Unfortunately, compliance with effective lipid therapies is poor. Whilst this is often the case with treatment for asymptomatic risk factors, there may also be a component due to drug side-effects. As a consequence, there is a need for more effective, better tolerated forms of treatment.
Some new lipid therapies illustrate the value of a “bedside to bench” approach. Microsomal Transfer Protein (MTP) Inhibitors, Pro-protein Convertase Subtilsin Kexin 9 (PCSK9) antibodies and Cholesterol Ester Transfer Protein (CETP) Inhibitors have direct clinical equivalents. Other novel drugs such as Mipomersin illustrate new therapeutic strategies that may find broader application. The mechanism of action of new lipid therapies will be considered with special attention to the issue of intra-cellular cholesterol homeostasis. Results of clinical trial with these new agents will be presented to illustrate a variety of outcomes ranging from encouraging surrogate endpoint success to termination of development due to inefficacy or side-effects. On-going endpoint studies will also be discussed.