Statins: Mechanisms of action & side effects
Authors: Rupali Manek, Julia Iftimie Reviewers: Gurreet Bhandal, Raafi Ali, Joshua Dian, Laura Byford-Richardson Samuel Fineblit*, Alexander Ah-Chi Leung* * MD at time of publication
Competitive inhibitors of HMG-CoA reductase (rate-limiting enzyme in cholesterol synthesis)
↓ Coenzyme Q10 (ubiquinone)
↑ Mitochondrial superoxide
↓ Hepatic membrane stability
↓ Conversion of HMG-CoA to mevalonic acid
↑ Hepatic VLDL uptake
↓ Hepatic apolipoprotein B-100 secretion
↓ Oxidative phosphorylation
Impaired mitochondrial function
↑ Liver enzyme leakage
↓ Mitochondrial ATP production
↑ Aminotransferases enzymes in liver
↑ Clearance of
LDL cholesterol from bloodstream
Myopathy/ myalgias (muscle aches)
Hepatotoxicity
↓ Circulating LDL cholesterol
↓ LDL, ↑ HDL, ↓ TG
↓ Hepatic cholesterol synthesis
↓ VLDL synthesis
↑ Cell surface LDL receptor expression
Statins
First line therapy for treating hypercholesterolemia (↑ LDL cholesterol in blood) Common examples: rosuvastatin, atorvastatin, simvastatin, pravastatin, etc.
↑ Apolipoprotein AI production & ↑ hepatic HDL neogenesis
↓ TG
↑ HDL
↑ Vasodilation
↓ C-reactive protein
↓ Impacts of coagulation cascade
↓ Atherosclerosis (plaque along walls of blood vessels)
↓ Cardiovascular disease & mortality
Pleotropic effects (i.e. non lipid related effects)
Abbreviations:
HMG-CoA – Hydroxymethylglutaryl-CoA LDL – Low-density lipoprotein
VLDL – Very low density lipoprotein HDL – High density lipoprotein
TG – Triglycerides
Inhibition of synthesis of isoprenoid intermediates in the mevalonate pathway
↑ Nitric oxide activity ↓ Inflammation
↓ Tissue factor expression
↓ Macrophage proliferation
↓ Tissue factor (promotes macrophage mediated thrombus formation)
↑ Blood flow & endothelial function
↓ Thrombin generation
↓ Metalloproteinases expression
↑ Inhibition of metalloproteinase-1
↓ Thrombogenicity (production of blood clot/thrombus)
Plaque stabilization (↓ risk of atherosclerotic plaque rupture, myocardial infarction, and stroke)
Legend:
Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
Physiological Outcome
Published July 9, 2017, updated Nov 6, 2023 on www.thecalgaryguide.com