Objectives. Inflammatory responses are closely knit with
low-density lipoprotein (
LDL)-cholesterol in driving
atherosclerosis. Even if
LDL-cholesterol is causative to atherosclerotic diseases and
LDL-cholesterol lowering reduces hard clinical endpoints, there is a residual risk for clinical events, possibly driven by inflammatory processes, in accordance with its role in
autoimmune diseases. Design. As
LDL-cholesterol treatment targets are reduced, the use of non-
statin lipid-lowering drugs will probably increase.
Atherosclerotic plaques evolve through
lipid infiltration and modification in the intima, furthermore infiltration of cells including monocytes, macrophages, T-lymphocytes and neutrophils initiating inflammatory signaling. Here we briefly review
inflammation in
atherosclerosis and the effects of the non-
statin lipid-lowering drugs on
inflammation. The review is limited to the most common non-
statin lipid lowering drugs, i.e.
proprotein convertase subtilisin-kexin type 9 (
PCSK9) inhibitors,
bile acid sequestrants (BAS) and
cholesterol absorption inhibitors. Results. PCSK9 inhibition is mostly studied together with
statins and is associated with a reduction of pro-inflammatory
cytokines. Furthermore,
PCSK9 inhibitors seem to have an effect on monocyte migration trough CCR2. They also have an interaction with
sirtuins, possibly offering a therapeutic target. BAS have several interesting effects on
inflammation, including reduction of pro-inflammatory
cytokines and a reduction of the number of infiltrating macrophages, however there are relatively few reports considering that these drugs have been on the market for decades.
Ezetimibe also has effects on
inflammation including reduction of pro-inflammatory
cytokines and adhesion molecules, however these effects are usually accomplished in tandem with
statins. Conclusion. This topic adds an interesting piece to the puzzle of
atherosclerosis, indicating that PCSK9 inhibition, BAS and
ezetimibe all affect
thromboinflammation.