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Current Drug Targets
ISSN (Print): 1389-4501
ISSN (Online): 1873-5592
VOLUME: 8
ISSUE: 3
DOI: 10.2174/138945007780058933      Price:  $58









Identifying and Attaining LDL-C Goals: Mission Accomplished? Next Target: New Therapeutic Options to Raise HDL-C Levels

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Author(s): Vasilios G. Athyros, Dimitri P. Mikhailidis, Anna I. Kakafika, Asterios Karagiannis, Apostolos Hatzitolios, Konstantinos Tziomalos, Emmanuel S. Ganotakis, Evangelos N. Liberopoulos and Moses Elisaf
Pages 483-488 (6)
Abstract:
Currently, low density lipoprotein cholesterol (LDL-C) levels are the main, if not the only, lipid target in the effort to reduce cardiovascular disease (CVD) morbidity and mortality. Several primary and secondary CVD prevention trials with statins shaped current guidelines and provided detailed targets across a range of CVD risk categories. These targets can be attained using effective statins or combination therapy. However, the net benefit in CVD risk reduction may be improved if we address other lipid risk factors. High density lipoprotein cholesterol (HDL-C) emerges from epidemiological studies as the most promising target. This review links the increase in HDL-C levels with clinical benefit from “old” (e.g. sustained release niacin) and new treatment options. Synthetically produced recombined apolipoprotein A-I Milano administered intravenously seems to have a marked effect in reducing the atheroma burden. The anti-cholesterol ester transfer protein (CETP) vaccine (CETi-1) produces auto-antibodies against CETP thus increasing the cholesterol ester content in HDL particles. CETP inhibitors (e.g. JTT-705 and torcetrapib) seem to be the most promising regimen to increase HDL-C levels. Torcetrapib (already in phase IIIa studies) can substantially increase HDL-C levels (up to 106%), alone or in combination with atorvastatin. HDL-C strategies, in combination with effective statins, are a new drug target aimed at a further reduction in CVD morbidity and mortality compared with statin monotherapy.
Keywords:
High density lipoprotein cholesterol, cardiovascular morbidity and mortality, niacin, CETP inhibition, torcetrapib
Affiliation:
Department of Clinical Biochemistry,Royal Free Hospital, Royal Free and University College School of Medicine, Pond Street, London NW3 2QG, United Kingdom.