• 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. Mucle toxicity may rarely manifest with rhabdomyolysis.


Statin Half-life in hours CYP-450 Bioavailability
Atorvastatin 15–30 CYP3A4 ∼ 10%
Simvastatin 2–3 CYP3A4, CYP3A5 ∼ 5%
Pravastatin ∼ 2 - ∼ 20%
Lovastatin 3 CYP3A4 ∼ 5%
Fluvastatin 0.5–2.5 CYP2C9 ∼20–30%
Pitavastatin 12 Limited CYP2C9 ∼ 50%
Rosuvastatin 19 Limited CYP2C9 ∼ 20%

Potency (and cost) increases in the following order: fluvastatin lovastatin and pravastatin simvastatin and atorvastatin!



Competitive inhibition of HMG-CoA reductase → reduced intrahepatic cholesterol biosynthesis → upregulation of expression of LDL receptor gene via sterol regulatory element-binding protein (SREBP)

  • ↓↓ LDL cholesterol (by ∼ 21–63%)
  • HDL cholesterol (by ∼ 5–10%)
  • triglyceride level (by ∼ 10–20%)
  • Pleiotropic effect: ↓ C-reactive protein, plaque stabilization; , ↑ anti-inflammatory effect, antioxidant effect and improved endothelial function of coronary arteries

Treatment of hyperlipidemia with statins significantly reduces the risk of mortality!


Side effects

  • General (common): headache and gastrointestinal symptoms (e.g., constipation, diarrhea, flatulence)
  • Hepatic (<1% 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
    • Statin-associated myopathy
      • Muscle pain and weakness
      • ↑ CK
      • May progress to rhabdomyolysis: rare but severe side-effect that may lead to myoglobulinuria AKI (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

Treatment must be discontinued if myopathy/rhabdomyolysis occurs!

Interaction with certain drugs (see below) can increase the risk of myopathy!

We list the most important adverse effects. The selection is not exhaustive.


→ For details see therapy of atherosclerotic disease and Guidelines for lipid-lowering therapy (ATP III guidelines)

Statins are the first-line therapy for hypercholesterolemia!



  • Hypersensitivity
  • Active liver disease
  • Muscle disorder
  • Pregnancy, breastfeeding


We list the most important contraindications. The selection is not exhaustive.


Maintain a high index of suspicion for rhabdomyolysis if muscle pain occurs after administering statins!

Guidelines & therapy recommendations

  • Ideally administered in the evenings (especially simvastatin)
  • Combination therapy with bile acid resins has a stronger hypolipidemic effect compared to treatment with statins alone; (both groups of drugs increase LDL receptor expression)


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last updated 09/25/2019
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