- Clinical science
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.
|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%|
- 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
Interaction with certain drugs can increase the risk of myopathy (see “Interactions” section below).
We list the most important adverse effects. The selection is not exhaustive.
- First-line treatment for patients with LDL cholesterol elevated ≥ 190 mg/dL
- Patients with a clinical atherosclerotic cardiovascular disease (includes , , and )
- Patients aged 40–75 with diabetes and LDL levels of 70–189 mg/dL
- Patients aged 40–75 with an estimated 10-year ASCVD risk ≥ 7.5% and LDL levels 70–189 mg/dL
For details, seeand
Statins are the first-line therapy for hypercholesterolemia.
- Other lipid-lowering agents
- CYP3A4 inhibitors