Statins

Key examples

• Simvastatin
• Atorvastatin
• Pravastatin
• Rosuvastatin

 

Common indications

1. Primary prevention of cardiovascular disease: to prevent cardiovascular events in people over 40 years of age with a 10-year cardiovascular risk >20.
2. Secondary prevention of cardiovascular disease: first line alongside lifestyle changes, to prevent further cardiovascular events in those who already have evidence of cardiovascular disease.
3. Primary hyperlipidaemia: first line, in conditions such as primary hypercholesterolaemia, mixed dyslipidaemia and familial hypercholesterolaemia.

 

Mechanisms of action

• Statins reduce serum cholesterol levels. They inhibit 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA) reductase, an enzyme involved in making cholesterol. They decrease cholesterol production by the liver and increase clearance of LDL-cholesterol from the blood, reducing LDL-cholesterol levels. 
• They also indirectly reduce triglycerides and slightly increase HDL-cholesterol levels. Through these effects they slow the atherosclerotic process and may even reverse it.

 

Important adverse effects

• Statins are generally safe and well tolerated. The most common adverse effects are headache and gastrointestinal disturbances. Potentially more serious are their effects on muscle. These can range from simple aches to more serious myopathy or, rarely, rhabdomyolysis. They can also cause a rise in liver enzymes (e.g. alanine transaminase [ALT]); drug-induced hepatitis is a rare but serious adverse effect.

 

Warnings

• Statins should be used with caution in patients with existing hepatic impairment. They are excreted by the kidneys, so the dose should be reduced in people with renal impairment. You should avoid prescribing statins to women who are pregnant (cholesterol is essential for normal fetal development) or breastfeeding.

 

Important interactions

• The metabolism of statins is reduced by cytochrome P450 inhibitors, such as amiodarone, diltiazem, itraconazole, macrolides and protease inhibitors. This leads to accumulation of the statin in the body, which may put patients at increased risk of adverse effects. Amlodipine has a similar interaction although the mechanism is less clear. 
• To reduce this risk you may need to reduce the dose of the statin or, if the other drug is being used for a short period only (e.g. a course of clarithromycin therapy), withhold the statin.