Evacetrapib, as monotherapy and combined with statins, not only increased total CEC, but also increased ABCA1-specific CEC and pre-beta-1 HDL. The mechanisms by which potent CETP inhibition increases ABCA1-specific CEC and pre-beta-1 HDL require further study. (A Study of LY2484595 in Patients With High LDL-C or Low HDL-C; NCT01105975).
Potent stimulation of PPAR-α leads to accelerated turnover of apoA-I and an increase in cholesterol efflux capacity in metabolic syndrome patients despite no change in HDL-C or apoA-I levels. This finding reinforces the notion that changes in HDL-C levels may poorly predict impact on functionality and thus has implications for ongoing pharmacologic efforts to enhance apoA-I metabolism.
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