Lipid Lowering Therapy for Atherosclerotic Cardiovascular Disease: It Is Not So Simple.

Plasma levels of atherogenic lipoproteins reflect a key risk factor for atherosclerotic cardiovascular disease ASCVD and treatments that lower these lipoproteins improve CV outcomes. Statins and PCSK9 inhibitors reduce LDL-C remarkably to low levels but do not eliminate residual cardiovascular risk as a result of other atherogenic lipoproteins or pathways for ASCVD, including inflammation, that are independent of LDL-C. Statins and PCSK9 inhibitors have complex mechanisms of action which appear to be additive and hence beneficial. Statin-intolerant subjects may benefit from ezetimibe, combination nutraceuticals and other drugs in development, while subjects with low LDL-C levels may benefit from anti-inflammatory drugs that target specific pathways. The future of pharmacotherapy for ASCVD will rely on a combination of drugs that reduce LDL-C and other atherogenic lipoproteins and drugs that target pathways including inflammation, endothelial function, vascular stiffness and anti-oxidant activity.