Novel agents for managing dyslipidaemia

An elevated low-density lipoprotein (LDL) cholesterol level is a strong pre dictor of coronary heart disease (CHD) risk. Over the past seven years, equ ally strong evidence has accumulated that lowering LDL cholesterol with HMG -CoA reductase inhibitors or statins reduces CHD risk and there is now wide spread use of these agents for the primary and secondary prevention of CHD. Treatment issues remain regarding the appropriate degree of LDL cholestero l reduction and whether, in people with very high levels, it would be prefe rable to achieve the LDL cholesterol goal with a powerful statin alone or c ombined with an agent that lowers LDL cholesterol by a different mechanism. The main focus in the development of novel agents is the patient with low high-density lipoprotein (HDL) cholesterol, usually associated with hypertr iglyceridaemia. Already prevalent as a risk factor for CHD, this abnormalit y has been linked with insulin resistance, which is likely to increase grea tly over the next decade, along with increasing obesity and diabetes. Agent s that have potent HDL cholesterol raising capacity include cholesteryl est er transfer protein (CETP) inhibitors, retinoid X receptor (RXR) selective agonists, specific peroxisome proliferator-activated receptor (PPAR) agonis ts and oestrogen-like compounds. Another area of development involves agent s that will lower both cholesterol and triglyceride levels, such as partial inhibitors of microsomal triglyceride transfer protein (MTP) and perhaps s qualene synthase inhibitors and agonists of AMP kinase. Future emphasis wil l be on correcting all lipid abnormalities for the prevention of CHD, not j ust lowering LDL cholesterol.