For more than 3 decades, since high levels of high-density lipoprotein cholesterol (HDL-C) were first linked to a lower risk of developing cardiovascular disease, the notion of raising HDL-C levels has been regarded as a potentially ideal treatment to prevent cardiovascular disease.1,2 High-density lipoprotein cholesterol has generally been called the “good cholesterol” to distinguish it from low-density lipoprotein cholesterol (LDL-C), which has been clearly linked to increased risk of cardiovascular disease and mortality. Although multiple large randomized trials have shown that lowering LDL-C leads to a reduction in cardiovascular events and mortality,3 for HDL-C, the translation from these observational studies to identifying a drug in randomized clinical trials that both increases HDL-C and reduces clinical events has been long and difficult. As such, the search for an HDL-C–raising, cardioprotective drug almost seems like the quest for the Holy Grail.
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