PCSK9 Forum: Lipid Lowering

Low density lipoprotein cholesterol (LDL-C) is a major modifiable risk factor driving the development of atherosclerosis and cardiovascular disease (CVD). While statins are effective in lowering LDL-C, attainment of LDL-C goal is problematic in individuals at high CV risk. These high risk individuals include those with inherited high cholesterol (familial hypercholesterolaemia, FH), established CVD and those unable to tolerate statin therapy, often due to muscle symptoms. New LDL-C lowering therapeutic options are needed to address the unmet clinical needs of these patients.

The discovery of PCSK9 (proprotein convertase subtilisin/kexin type 9), a protein which plays a pivotal role in controlling circulating LDL-C levels, has been the driver for the development of a new class of LDL-C lowering agents. PCSK9 binds to the LDL receptor on the cell and blocks the recycling of LDL receptors, leading to higher LDL-C levels in the plasma. Therefore, inhibiting PCSK9 would lead to increased availability of LDL-C receptors and in turn lower LDL-C levels.

The first agents in this new class, monoclonal antibodies targeting PCSK9 (alirocumab and evolocumab), have recently received regulatory approval in the US and Europe. These agents have been shown to be highly effective in lowering LDL-C levels by more than 50%, on top of statin and other lipid‐lowering treatment, with consistent response across the spectrum of high CV risk patients. PCSK9 inhibitors also lower lipoprotein(a), another established CV risk factor. The PCSK9 monoclonal antibody therapies offer a new approach to getting high CV risk patients to LDL-C goal.

With the advent of this novel therapeutic class, there is a need for an accessible resource which summarises what clinicians need to know about PCSK9. PCSK9 Forum is the independent online resource on PCSK9 science and clinical application, established by leading researchers in the fields of atherosclerosis, lipids and CVD. This Handbook, authored by PCSK9 Forum Editors Professors Chapman and Ginsberg, provides a unique accessible reference for clinicians. The Handbook discusses the biology of PCSK9, and how the development of PCSK9 inhibitors will revolutionise the management of these high CV risk patients, in particular those with FH. The Handbook also provides an overview of the clinical evidence for the most advanced of these novel agents, covering both efficacy and safety. This easy to read, comprehensive resource will help clinicians in their everyday practice to address the unmet clinical needs of patients at high CVD risk.