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.