Title:Lipid-Lowering Therapies for Atherosclerosis: Statins, Fibrates, Ezetimibe and PCSK9 Monoclonal Antibodies
Volume: 28
Issue: 36
Author(s): Adel Hajj Ali, Nour Younis, Rola Abdallah, Farah Shaer, Ali Dakroub, Mohammed Akli Ayoub, Rabah Iratni, Hadi Mohamad Yassine, Kazem Zibara, Alexander Orekhov, Ahmed Fawzy El-Yazbi and Ali H. Eid *
Affiliation:
- Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, P.O. Box 2713,Qatar
Keywords:
Atherosclerosis, statin, fibrates, ezetimibe, PCSK9 inhibitors, microRNA inhibitors, monoclonal antibodies
for atherosclerosis.
Abstract: Cardiovascular disease (CVD) remains the primary cause of global morbidity
and mortality. CVD includes various life-threatening conditions such as myocardial infarction,
stroke and peripheral arterial diseases. In this context, atherosclerosis continues
to play the principal role in the pathogenesis of these conditions. Atherosclerosis emanates
from a set of modifiable and non-modifiable risk factors that include age, male gender,
family history, obesity, smoking, diabetes mellitus and hypertension. Recent evidence
classifies atherosclerosis as a latent disease affecting all-sized arteries with a
predilection for arterial branching points of decreased or absent blood supply. Atherosclerosis
is not only a lipid metabolism disorder, but is also a chronic inflammatory one. This
review providesa synoptic discussion of the underlying pathological mechanisms of
atherosclerosis andthe currently applied therapeutic interventions. We then discuss the
classical lipid-lowering therapies as well as the newly discovered therapies. For the classical
therapies, we point out the importance of statins and ezetimibe in reducing plasma
cholesterol levels by virtue of their effects on synthesis, reuptake and intestinal absorption
of cholesterol. We also discuss the role of fibrates in modulating lipid metabolism
and improving the ratio of high-density to low-density density lipoproteins. This study focuseson
the more recent molecular and genetic interventions exemplified by proprotein
convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies, evinacumab, and microRNA
inhibitors. Special attention is also given to clinical trials involving these therapies.