Keele Research Repository

The association between cardiovascular disease (CVD) risk and raised serum total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C) has been demonstrated in epidemiology1 and intervention trials showing significant decreases in CVD following use of LDL-C reducing agents such as statins and ezetimibe and has given rise to the LDL hypothesis2. However, even with statin / ezetimibe combination treatment, many patients fail to achieve lipid reduction targets. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are monoclonal antibodies that bind and inactivate PCSK9, leading to decreased LDL receptor degradation and hence enhanced LDL receptor recycling back to the liver surface (up to 150 times) and increased LDL uptake3. PCSK9 inhibition was identified as a potential modifier of CVD risk as loss of function mutations in the PCSK9 gene?? were associated with low LDL-C and reduced CVD4, We will explore efficacy (trials and in an out-patient setting) and outcome evidence with emphasis on patients with diabetes (DM) especially type 2 diabetes (T2DM).