Novel Therapies Focused on the High-Density Lipoprotein Particle

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Cardiovascular disease (CVD) remains a major burden for morbidity and mortality in the general population, despite current efficacious low-density lipoprotein-cholesterol-lowering therapies. Consequently, novel therapies are required to reduce this residual risk. Prospective epidemiological studies have shown that high-density lipoprotein-cholesterol (HDL-C) levels are inversely correlated with cardiovascular disease risk, and this initiated the quest for HDL-C-increasing therapies. Consequently, several different targets in HDL metabolism have been identified. Initial studies addressing the effect of cholesteryl ester transfer protein inhibition on cardiovascular disease outcome have been discontinued for reasons of futility or increased mortality. As of yet, 2 cholesteryl ester transfer protein inhibitors are still in phase III studies. Other HDL-based interventions, such as apolipoprotein A1-based compounds, ABC-transporter upregulators, selective peroxisome proliferator-activated receptor modulators and lecithin-cholesterol acyltransferase-based therapy, hold great promise for the future. The aim of this review is to provide a comprehensive overview of HDL-targeted pharmaceutical strategies in humans, both in early development as well as in late stage clinical trials
Original languageEnglish
Pages (from-to)193-204
JournalCirculation Research
Issue number1
Publication statusPublished - 2014

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