Statins

Statins are a group of medications primarily used to lower cholesterol levels in the blood. ¹ Specifically, they target and reduce “bad” cholesterol (LDL) while often increasing “good” cholesterol (HDL)

Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications used to manage and prevent cardiovascular diseases. They work by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver.

Mechanism of Action

• Cholesterol production: Statins inhibit an enzyme in the liver that is responsible for producing cholesterol.   1. HMG-CoA Reductase Inhibitors – StatPearls – NCBI Bookshelf www.ncbi.nlm.nih.gov
• LDL reduction: By blocking cholesterol production, the liver removes more LDL from the bloodstream to compensate.   1. HMG-CoA Reductase Inhibitors – StatPearls – NCBI Bookshelf www.ncbi.nlm.nih.gov
• Plague build-up: Lowering LDL cholesterol helps prevent the build-up of plaque in the arteries, reducing the risk of heart attack and stroke

Statins inhibit HMG-CoA reductase, the enzyme responsible for converting HMG-CoA to mevalonate, a precursor of cholesterol. This inhibition reduces cholesterol synthesis in the liver, leading to increased clearance of low-density lipoprotein (LDL) cholesterol from the bloodstream.

Clinical Uses

Statins are primarily used for:

1. Primary Prevention: Reducing the risk of cardiovascular events in individuals with risk factors such as diabetes, hypertension, and a family history of cardiovascular disease.
2. Secondary Prevention: Reducing the risk of recurrent cardiovascular events in individuals with established cardiovascular disease, including coronary artery disease, stroke, and peripheral artery disease.
3. Hyperlipidemia: Managing high levels of LDL cholesterol and total cholesterol.

Common Statins

1. Atorvastatin (Lipitor)
   • Dose: 10-80 mg orally once daily.
   • Uses: Primary and secondary prevention of cardiovascular events, and hyperlipidemia.
   • Adverse Effects: Myopathy, elevated liver enzymes, gastrointestinal symptoms.
   • Contraindications: Active liver disease, pregnancy, breastfeeding.
2. Simvastatin (Zocor)
   • Dose: 10-40 mg orally once daily in the evening.
   • Uses: Primary and secondary prevention of cardiovascular events, and hyperlipidemia.
   • Adverse Effects: Myopathy, rhabdomyolysis (rare), elevated liver enzymes.
   • Contraindications: Active liver disease, pregnancy, breastfeeding, concomitant use with strong CYP3A4 inhibitors.
3. Rosuvastatin (Crestor)
   • Dose: 5-40 mg orally once daily.
   • Uses: Primary and secondary prevention of cardiovascular events, and hyperlipidemia.
   • Adverse Effects: Myopathy, elevated liver enzymes, headache.
   • Contraindications: Active liver disease, pregnancy, breastfeeding.
4. Pravastatin (Pravachol)
   • Dose: 10-80 mg orally once daily.
   • Uses: Primary and secondary prevention of cardiovascular events, and hyperlipidemia.
   • Adverse Effects: Myopathy, gastrointestinal symptoms, headache.
   • Contraindications: Active liver disease, pregnancy, breastfeeding.
5. Lovastatin (Mevacor)
   • Dose: 20-80 mg orally once daily in the evening.
   • Uses: Primary and secondary prevention of cardiovascular events, and hyperlipidemia.
   • Adverse Effects: Myopathy, elevated liver enzymes, gastrointestinal symptoms.
   • Contraindications: Active liver disease, pregnancy, breastfeeding, concomitant use with strong CYP3A4 inhibitors.
6. Fluvastatin (Lescol)
   • Dose: 20-80 mg orally once daily.
   • Uses: Primary and secondary prevention of cardiovascular events, and hyperlipidemia.
   • Adverse Effects: Myopathy, elevated liver enzymes, gastrointestinal symptoms.
   • Contraindications: Active liver disease, pregnancy, breastfeeding.

Adverse Effects

• Common: Myopathy, elevated liver enzymes, gastrointestinal symptoms (nausea, diarrhea, constipation).
• Serious: Rhabdomyolysis (rare but serious muscle damage), liver failure (very rare).
• Monitoring: Liver function tests before and during treatment, CK (creatine kinase) levels if symptoms of myopathy occur.

Contraindications

• Active liver disease.
• Pregnancy and breastfeeding.
• Hypersensitivity to statins.
• Concomitant use with certain drugs (e.g., strong CYP3A4 inhibitors with simvastatin and lovastatin).

Drug Interactions

• CYP3A4 Inhibitors: Increase the risk of statin toxicity (e.g., clarithromycin, ketoconazole).
• Fibrates: Increase the risk of myopathy and rhabdomyolysis.
• Warfarin: Statins can enhance the anticoagulant effect, requiring careful monitoring of INR.

Clinical Guidelines

In the UK, the National Institute for Health and Care Excellence (NICE) provides guidelines on the use of statins:

1. Primary Prevention:
   • Statins are recommended for adults with a 10-year cardiovascular risk of 10% or more (measured using the QRISK3 tool).
   • Atorvastatin 20 mg is the usual starting dose for primary prevention.
2. Secondary Prevention:
   • Statins are recommended for all adults with established cardiovascular disease.
   • Atorvastatin 80 mg is the usual dose for secondary prevention.
3. Monitoring and Review:
   • Lipid levels should be measured before starting treatment, at 3 months, and annually thereafter.
   • Liver function tests should be performed before starting treatment, at 3 months, and 12 months.

References

1. NHS: Statins
2. https://www.ncbi.nlm.nih.gov/books/NBK542212/#:~:text=The%20proposed%20mechanism%20is%20that,1%2C%20which%20mediates%20glucose%20uptake