Statins are the lipid-lowering drugs of choice. Statins reduce hepatic cholesterol synthesis by inhibiting enzyme HMG-CoA reductase. This leads to a consequent upregulation of LDL receptors on hepatocytes, which, in turn, lowers LDL cholesterol levels and triglycerides while raising HDL cholesterol. Headache and gastrointestinal side-effects are common. Statins carry a risk of hepatic and muscle toxicity. Muscle toxicity may rarely manifest with rhabdomyolysis.
For a comparison of statins with other lipid-lowering agents, see “Overview of lipid metabolism and lipid-lowering agents.”
|Overview of statin pharmacokinetics|
|Statin||Half-life in hours||CYP-450||Bioavailability |
|Simvastatin||2–3||CYP3A4, CYP3A5||∼ 5%|
|Pravastatin||∼ 2||-||∼ 20%|
|Pitavastatin||12||Limited CYP2C9||∼ 50%|
|Rosuvastatin||19||Limited CYP2C9||∼ 20%|
“Flo Loves Prague Since A Tour of Russia.” Lipid-lowering potency increases in the following order: Fluvastatin → Lovastatin → Pravastatin → Simvastatin → Atorvastatin → Rosuvastatin
- Competitive inhibition of HMG-CoA reductase renders this enzyme unable to convert HMG-CoA to mevalonate (the rate-limiting step of cholesterol synthesis) → reduced intrahepatic cholesterol biosynthesis → upregulation of expression of LDL receptor gene via sterol regulatory element-binding protein (SREBP) → increased LDL recycling and: 
- Pleiotropic effect:
- General (common): headache and gastrointestinal symptoms (e.g., constipation, diarrhea, flatulence)
- Hepatic: (up to 3% of patients) ↑ LFTs due to the involvement of cytochrome P450 systems (CYP3A4 and CYP2C9) in the breakdown of statins 
Muscular: Statins decrease the synthesis of coenzyme Q10 and impair energy production within the muscle.
- Myalgia (muscle pain): continue treatment as long as creatinine phosphokinase (CK) remain normal
- Muscle pain and weakness, especially when used alongside fibrates or niacin
- Myositis: ↑ CK
- May progress to rhabdomyolysis: rare but severe side-effect that may lead to myoglobulinuria → (↑ BUN and ↑ creatinine)
- Management: discontinue statin therapy for 2–4 weeks; start treatment with a low-dose statin (e.g., pravastatin or fluvastatin) once symptoms have resolved
We list the most important adverse effects. The selection is not exhaustive.
- High-intensity statins 
- Low- to moderate-intensity statins: primary prevention of 
For details, seeand
Statins are the first-line therapy for hypercholesterolemia.
We list the most important contraindications. The selection is not exhaustive.
- Other lipid-lowering agents
- CYP3A4 inhibitors