Discussion
The clinical effects of statins in reducing mortality in patients with a
history of cardiovascular events are related to their pleiotropic
effects (4); which means in addition to the cholesterol-lowering effect,
they have extra effects which are responsible for clinical benefits in
patients with CVD. These effects include increasing myocardial perfusion
and reducing recurrent anginal episodes after acute chronic events by
modulation of endothelial function, plaque stabilization,
neovascularization, attenuated atherogenesis, neurohormonal imbalance
improvement, decreasing oxidative stress, vascular inflammation, and
antithrombotic action (1,4).
Proposing an alternative drug in patients who require receiving
secondary prophylaxis for cardiovascular events considered a serious
challenge, especially in case of side effects such as recurrent
tendinopathy, which requires statin discontinuation.
Proprotein convertase subtilisin/Kexin type 9 (PCSK9) inhibitors are one
of the hypolipidemic classes that have Food and Drug Administration
(FDA) approval for treatment of autosomal familial hypercholesterolemia.
Evolocumab, Alirocumab, and Cocizumab are well-known PCSK9 inhibitors.
Their main mechanism of action is to increase LDL receptors on
hepatocytes by inhibiting PCSK9, which is responsible for the inhibition
of LDL-receptor (5).
The pleiotropic effects of this family, beyond the lipid-lowering
effects, include inhibition of atherogenesis, stabilization of
atherosclerotic plaque, anti-inflammatory effects by increasing the
concentration of interleukin 10 (IL-10) and decreasing the concentration
of interleukin-1ɑ (IL-1ɑ), interleukin-6 (IL-6) and tumor necrosis
factor ɑ (TNF-ɑ), anti-aggregation and anticoagulant effect (5).
Due to their effects in reducing cardiovascular events and all-cause
mortality in very high-risk atherosclerotic cardiovascular disease
(ASCVD) patients (5–7), they can be considered as a suitable
alternative in patients with statin intolerance.