ATP citrate lyase (ACLY, bempedoic acid) and NPC1L1 (ezetimibe)

Class

Fixed-dose combination: ATP citrate lyase inhibitor + cholesterol absorption inhibitor

Pathway

Dual LDL-C lowering via inhibited hepatic cholesterol/fatty-acid synthesis upstream of HMG-CoA reductase (ACLY inhibition) and blocked intestinal cholesterol absorption (NPC1L1 inhibition)

This combination pairs two agents that lower low-density lipoprotein cholesterol (LDL-C) by different but complementary routes. ATP citrate lyase (ACLY) is an enzyme in the liver that supplies building blocks for cholesterol synthesis; blocking it reduces the liver's own cholesterol output, prompting liver cells to pull more LDL particles out of the bloodstream. NPC1L1 is a transporter in the intestinal lining that absorbs dietary and bile-derived cholesterol; blocking it reduces how much cholesterol enters the body from the gut. Used together, the two mechanisms act on separate sources of cholesterol supply—hepatic production and intestinal uptake—so their effects are additive rather than redundant. This dual approach is relevant wherever LDL-C reduction is a therapeutic goal, particularly in patients with elevated cardiovascular risk who have not reached target cholesterol levels through diet or other lipid-lowering therapy alone, or who cannot tolerate certain other cholesterol-lowering approaches. Because both mechanisms converge on the shared endpoint of increasing LDL receptor activity in the liver, combining them offers a way to achieve meaningful LDL-C reduction while potentially using lower doses of each component than would be required from either drug alone.