The modern history of cholesterol-lowering drugs started in 1972 when Dr. Akira Endo
identified an active compound (compactin) that inhibited cholesterol biosynthesis
from the culture broth of blue-green mold (Penicillium citrinum Pen-51). Since 1987,
statins have represented the milestone for the treatment of atherosclerotic cardiovascular
disease. A new therapy for the treatment of hypercholesterolemia since the discovery
of statins is ezetimibe, the first and only agent inhibiting intestinal cholesterol
absorption. Ezetimibe was approved by the FDA in October 2002. A year later, the association
between gain-of-function PCSK9 genetic mutations and hypercholesterolemia was reported,
and this discovery opened a new era in lipid-lowering therapies. Monoclonal antibodies
and small-interfering RNA approaches to reduce PCSK9 were developed and approved for
clinical use in 2015 and 2022, respectively. Finally, the newly approved bempedoic
acid, an oral adenosine triphosphate citrate lyase inhibitor that lowers LDL-C, is
able to reduce major adverse cardiovascular events in both primary and secondary prevention.
In the present narrative review, we summarize the pharmacological properties and the
clinical efficacy of all these agents currently used for a tailored therapy of hypercholesterolemia
in patients with atherosclerotic cardiovascular disease.