Positioning of PCSK9 Inhibitors in hypercholesterolemia

Abstract

PCSK 9 inhibitors currently have a market of 3 billion USD and by next 10 years it will raise to 13 billion USD in developed world. The rising prevalence of dyslipidemia and other lipid disorders are linked to lipid metabolism due to an unbalanced lifestyle and rising alcohol and tobacco use. PCSK9 inhibitors are injectable monoclonal antibodies that inactivate PCSK9 receptors. PCSK9 inhibition decreases degradation of the LDL receptor, thus raising the number of functioning LDL receptors on hepatocytes and lowering the number of LDL particles in the blood, which are atherogenic. For patients with very high cardiovascular risk, PCSK9 inhibitors and ezetimibe are added to statins, where they significantly lower absolute risk for myocardial infarction (MI) and stroke. Statins are known to upregulate PCSK9 encoding gene. PCSK9 inhibitors are given bimonthly or monthly and are reasonably safe. Familial Hypercholesterolemia (FH) a common inherited disorder of lipid metabolism, has mutations in one of these 3 genes: LDLR, APOB or PCSK9. These patients have 22 times more risk of coronary event than general population. Addition of a PCSK9 inhibitor to low dose statin therapy will be more effective in lowering LDL and avoiding the side effects of statins. PCSK9 inhibitors can contribute to both the stabilization and regression of atherosclerotic plaques and thereby avoid or delay major adverse cardiac events.