Title:PCSK9 Inhibition in Atherosclerotic Cardiovascular Disease
Volume: 29
Issue: 23
Author(s): Dimitrios Delialis, Maria-Angeliki Dimopoulou, Maria Papaioannou, Georgia Kotsira, Eleni Maneta, Georgios Mavraganis, Christos Loutos, Georgios Georgiopoulos and Kimon Stamatelopoulos*
Affiliation:
- Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
Keywords:
PCSK9 inhibitors, evolocumab, alirocumab, inclisiran, coronary artery disease, atherosclerosis, acute coronary syndrome.
Abstract: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) represent a novel class of hypolipidemic
drugs, providing an additional therapeutic option over conventional hypolipidemic treatments. Given
the constantly lowering recommended LDL-C goals, low goal achievement rate and low compliance with
treatment, new hypolipidemic drug classes may substantially contribute to residual risk reduction for atherosclerotic
cardiovascular disease (ASCVD). This review aims to summarize contemporary evidence on the clinical
role of PCSK9i in ASCVD prevention. PubMed and MEDLINE databases were searched for keywords in
studies on PCSK9i and ASCVD. Approved PCSK9i are the monoclonal antibodies (Mabs), evolocumab and
alirocumab, targeting PCSK9, and inclisiran, a small interfering RNA inhibiting PSCK9 synthesis. Overall,
PCSK9i effectively reduced LDL-C and other atherogenic lipoproteins, including apolipoprotein B and lipoprotein(
a) primarily. PSCK9i Mabs improved imaging markers reflecting coronary atherosclerotic plaque vulnerability
and reduced ASCVD events in high-risk patients after short-term treatment (< 3 years follow-up). They
are currently indicated as a third-line treatment for secondary prevention and primary prevention in patients
with familial hypercholesterolemia at high risk of not achieving their LDL-C goals. Patients with higher baseline
ASCVD risk receive greater benefits from PCSK9i. Recent evidence suggests that evolocumab was effective
and safe after long-term treatment. Ongoing trials investigate new therapeutic indications for PCSK9i while
their cost-effectiveness is still being considered. PCSK9i is a novel hypolipidemic drug class currently indicated
for reducing residual risk in secondary ASCVD prevention and high-risk patients.
