PCSK9 Inhibitors: Research and new perspectives in clinical practice

E. Charatsi, I. Tsigeridis



Statins are the cornerstone of hypolipidemic treatment. However, there are cases with no satisfactory results, as when statin intolerance occurs or LDL target is very low. PCSK9 inhibitors are a new drug category, promising to cover this treatment gap. They are monoclonal antibodies which get attached to PCSK9 protein and prevent its binding to LDL receptors on the hepatocyte surface. Consequently, LDL receptors are free to withdraw LDL cholesterol from blood. Evolocumab and alirocumab are the two drugs approved by FDA and EMA for patients with familial hypercholesterolemia or patients with very high cardiovascular risk on statin treatment who haven’t reached LDL target. PCSK9 inhibitors can lower LDL cholesterol up to levels of 20 mg/dL or 10 mg/dL. This is not an unusual or extreme effect, as normal LDL cholesterol values less than 50 mg/dL have been found in some native human population groups and wild mammals. On-going trials achieving LDL cholesterol levels less than 20 mg/dL have already shown very important cardiovascular benefit in post-hoc analysis. Safety of new drugs compared to placebo seems acceptable but final conclusions will be drawn when studies are completed.

Keywords: evolocumab, alirocumab, PCSK9, hyperlipidemia, evolocumab, alirocumab, PCSK9