Current, new and future treatments in dyslipidaemia and atherosclerosis

The new therapeutic options available to clinicians treating dyslipidaemia in the last decade have enabled effective treatment for many patients. The development of the HMG-CoA reductase inhibitors (statins) have been a major advance in that they possess multiple pharmacological effects (pleiotropic effects) resulting in potent reductions of low density lipoproteins (LDL) and prevention of the atherosclerotic process. More recently, the newer fib ric acid derivatives have also reduced LDL to levels comparable to those ac hieved with statins, have reduced triglycerides, and gemfibrozil has been s hown to increase high density lipoprotein (HDL) levels. Nicotinic acid has been made tolerable with sustained-release formulations, and is still consi dered an excellent choice in elevating HDL cholesterol and is potentially e ffective in reducing lipoprotein(a) [Lp(a)] levels, an emerging risk factor for coronary heart disease (CHD). Furthermore, recent studies have reporte d positive lipid-lowering effects from estrogen and/or progestogen in postm enopausal women but then are still conflicting reports on the use of these agents in dyslipidaemia and in females at risk for CHD. In addition to lowe ring lipid levels, these antihyperlipidaemic agents may have directly or in directly targeted thrombogenic, fibrinolytic and atherosclerotic processes which may have been unaccounted for in their overall success in clinical tr ials. Although LDL cholesterol is still the major target for therapy, it is likel y that over the next several years other lipid/lipoprotein and nonlipid par ameters will become more generally accepted targets for specific therapeuti c interventions. Some important emerging lipid/lipoprotein parameters that have been associated with CHD include elevated triglyceride, oxidised LDL c holesterol and Lp(a) levels, and low HDL levels. The nonlipid parameters in clude elevated homocysteine and fibrinogen, and decreased endothelial-deriv ed nitric oxide production. Among the new investigational agents are inhibi tors of squalene synthetase, acylCoA: cholesterol acyltransferase, choleste ryl ester transfer protein, monocyte-macrophages and LDL cholesterol oxidat ion. Future applications may include thyromimetic therapy, cholesterol vacc ination, somatic gene therapy, and recombinant proteins, in particular, apo lipoproteins A-I and E. Non-LDL-related targets such as peroxisome prolifer ator-activating receptors, matrix metalloproteinases and scavenger receptor class B type I may also have clinical significance in the treatment of ath erosclerosis in the near future. Before lipid-lowering therapy, dietary and lifestyle modification is and sh ould be the first therapeutic intervention in the management of dyslipidaem ia. Although current recommendations from the US and Europe are slightly di fferent, adherence to these recommendations is essential to lower the risk of atherosclerotic vascular disease, more specifically CHD. New guidelines that are expected in the near future will encompass global opinions from th e expert scientific community addressing the issue of target LDL goal (aggr essive versus moderate lowering) and the application of therapy for newer e merging CHD risk factors.