The treatment of dyslipidemia--what's left in the pipeline?

Abstract

Dyslipidemia is a pathological alteration of serum lipid levels. The most common forms are either elevations of triglycerides or low density lipoprotein cholesterol associated with a reduction of high density lipoprotein cholesterol. Most frequently both forms of lipid disorders are combined. Elevations of free fatty acid blood levels are commonly not subsumed under the term dyslipidemia. However, free fatty acids should also be considered, as they are frequently associated with dyslipidemia and represent a risk factor for cardiovascular diseases. Dyslipidemias are among the major etiologic factors for arterial occlusive diseases. Resulting in fatal implications such as stroke and coronary heart disease, dyslipidemias contribute to the most prevalent causes of death. Lowering of low density lipoprotein and raising of high density lipoprotein cholesterol levels have been shown in both epidemiologic and intervention studies to decrease mortality. Established treatments of dyslipidemias are statins and fibrates. However, recent research has established some new potential therapeutic targets which are currently investigated in clinical trials. New therapeutic approaches include subtype selective, dual, and pan-agonists of the peroxisome proliferator activated receptor, inhibitors of the cholesterol ester transfer protein, Acyl-CoA-cholesterol-acyltransferase, squalene synthase, microsomal triglycerid-transfer-protein, and cholesterol absorption. Clinical implications of new drugs under investigation are discussed in this review.