What it is
Atorvastatin is a high-intensity lipophilic statin and one of the most prescribed in the world. It inhibits HMG-CoA reductase, the key enzyme in the liver's cholesterol synthesis. Depending on the dose, it lowers LDL cholesterol by 35 to 55%, raises HDL slightly and lowers triglycerides.
It is first line in hypercholesterolaemia and in cardiovascular prevention, both primary and secondary. It is generally well tolerated. Unlike simvastatin, because of its long half-life it can be taken at any time of day.
Mechanism of action
It works by inhibiting:
- It competitively inhibits liver HMG-CoA reductase
- It reduces the liver's synthesis of cholesterol
- The liver makes more LDL receptors and removes more LDL from the blood
At the counter
When to recommend it
- Primary hypercholesterolaemia (LDL above the target for the person's risk)
- Secondary prevention after a heart attack or stroke
- Heterozygous familial hypercholesterolaemia
- Diabetes with atherogenic dyslipidaemia
When not to
- Known allergy to statins
- Active liver disease
- Severe pre-existing myopathy
- Pregnancy and breastfeeding
Warnings
- Important Myopathy: rare but serious. Widespread muscle pain, weakness, dark urine (rhabdomyolysis). Warn the patient.
- Important Rhabdomyolysis: very rare but potentially fatal. Higher risk with high doses + CYP3A4 inhibitors.
- Caution Raised liver enzymes: check ALT/AST at baseline. Usually mild and reversible.
- Caution Mild muscle aches: common and generally tolerable. They need to be told apart from myopathy (weakness, dark urine).
Pharmacokinetics
- Absorption
- Rapid oral absorption. Bioavailability of 14% (first-pass metabolism). Peak at 1–2 hours.
- Distribution
- Distributed mainly to the liver (its site of action). Protein binding of 98%. It does not significantly cross the blood–brain barrier.
- Metabolism
- Extensive hepatic metabolism via CYP3A4. It produces active metabolites that contribute to the cholesterol-lowering effect.
- Elimination
- Biliary elimination. Half-life of about 14 hours.
Atorvastatin vs simvastatin
| Aspect | Atorvastatin | Simvastatin |
|---|---|---|
| LDL-lowering potency | High (35–55%) | Moderate (25–40%) |
| CYP3A4 metabolism | Subject to inhibition | Very subject to inhibition |
| Interactions | Moderate | Many |
| Effect on HDL | Good (+5–10%) | Moderate |
| First line today | Yes | No (second line) |
Atorvastatin is first line because of its potency and better safety profile. Simvastatin has more interactions.
Self-assessment
Three questions. When you check your answers you will see the explanation for each one.
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Atorvastatin is an HMG-CoA reductase inhibitor. It reduces cholesterol synthesis in the liver, which increases the uptake of circulating LDL.
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Muscle pain plus a statin must be assessed: if it is myopathy (raised CK), the statin is stopped. It is rare but serious.
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Its long half-life (about 14 hours, and longer for its active metabolites) covers the whole day, so the time does not matter: regularity does. The one worth taking at night is simvastatin, which has a short half-life.
Training content. It does not replace the summary of product characteristics or clinical judgement.