Dyslipidemia management update

- Statins reduce the risk of ASCVD by decreasing the biosynthesis of cholesterol.
- PCSK9 antibodies are used as an add-on therapy to further reduce cholesterol levels in patients receiving optimized statin therapy.
- Apo B-100 and MTP inhibitors are used to treat patients with HoFH.

Association of hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD) is well established. Reducing low-density lipoprotein-cholesterol (LDL-C) and raising high-density lipoprotein-cholesterol (HDL-C) have been the therapeutic targets to reduce the risk of ASCVD. Cholesterol-lowering medications have been used to provide both primary and secondary prevention of ASCVD for many years by reducing the absorption and reabsorption, promoting excretion, or decreasing the synthesis of cholesterol. Within the past five years, several new classes of cholesterol-lowering drugs have been tested and approved for patients with hypercholesterolemia that are not well controlled by conventional therapy (ezetimibe, bile-acid sequestrants, and statins). These drugs include proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies, apolipoprotein A-100 (Apo B-100) antisense, and microsomal triglyceride transfer protein (MTP) inhibitor. Clinical trials revealed that adding PCSK9 antibodies to the preexisting statin therapy can further reduce LDL-C by 60%. ApoB antisense and MTP inhibitor are currently approved for patients with homozygous familial hypercholesterolemia. Several HDL-raising drugs have also been tested, but the results are not promising. Studies suggest that specifically raising reverse cholesterol transport rather than HDL-C level could be a novel therapeutic approach to reduce cardiovascular risk.