Lege Artis Medicinae

[New possibilities in treating hyperlipidemia]

CSÁSZÁR Albert

FEBRUARY 22, 2013

Lege Artis Medicinae - 2013;23(02)

[In the fight against atherosclerosis, statin therapy is one of the most important elements. On the basis of data from the past few years the clinical introduction of a more effective statin is not expected, however, in order to improve cardiovascular prevention further development of agents that reduce LDL-cholesterol levels more effectively than currently used statins is warranted. The need for the development of new cholesterol-lowering therapeutic options is also supported by the existence of statin intolerance. The currently available combination therapies do not provide additional mortality benefits compared with statin monotherapy. The new solutions include fourth-generation statin molecules that primarily aim to enhance the NO-donor capacity of statins, and to reduce their muscle toxicity. Certain compounds that affect cholesterol synthesis (squalene synthase inhibitors, MTP inhibitors, ACAT inhibitors) need to be further analysed because of the risk of side effects. The use of an antisense oligonucleotid that blocks the mRNA of apoB, the main protein on the LDL-particle and antibodies that inhibit the protein PCSK9 that promotes the intracellular breakdown of the LDL-receptor seems to be much more promising. Besides the lowering of LDLcholesterol level, studies have focused on the benefits of increasing HDL-cholesterol levels. Unfortunately, recently completed analyses show that new forms of the strong HDL-C increasing nicotinic acid have not provided any additional benefit when added to statin therapy. Similarly, the adverse effects associated with the promising CETP inhibitors and the lack of additional benefit when combined with statins question the significance of this drug class. The necessity for an absolute increase of HDL-cholesterol levels needs to be revised on the basis of new data, in other words, the exact role of the HDL particle in atherosclerosis needs to be further investigated.]

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