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Perspectives of the non-statin hypolipidemic agents
Rozman, Damjana, 1960- ; Monostory, Katalin
This review focuses on the non-statin strategies for treatment of hyperlipidemias in humans. Even if statins remain the major hypolipidemic drugs at present, an increasing number of patients that are ...treated with statins raises as well the numbers of patients suffering from side effects or not responding well to the therapy. Thus, development of novel approaches to battle the world epidemics of hyperlipidemia remains relevant. The non-statin strategies include decrease of cholesterol absorption from the diet, lowering the atherogenic lipoprotein release and increasing HDL levels, or increasing elimination of cholesterol by bile acid binding. Representative non-statin drugs that are on the market or are in development phases are described hereinin comparison to statins. In addition to 3beta-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), as the major regulatory enzyme of cholesterol synthesis that is the target of statins, some other enzymes of this multi-steppathway represent perspective targets for development of novel hypolipidemics. None of these inhibitors is currently approved for use in humans. We describe characteristics of the later enzymes of cholesterol synthesis, starting from the squalene synthase step. Inhibitors of these enzymes are critically evaluated, particularly concerning safety in humans (teratogenic potential, toxicity, other side effects) and their hypolipidemic effects compared to the statins. Since only a limited number of publications discuss the non-statin approaches for treatment of hyperlipidemias, this review represents a valuable up-to date summary, with a take-home message, that novel approaches deserve more attention in the future, irrespective of the success of statins.
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