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Statins are enzyme inhibitors and have a direct action on the biosynthesis of cholesterol in the liver. They reduce coronary and cardiovascular events and total mortality (BMA/RPSGB, 2004).

Statins are being used increasingly in the primary and secondary prevention of cardiovascular disease. One product, simvastatin, has now become available over the counter from pharmacists. Primary prevention refers to patients who have one or more cardiovascular risks, but do not show overt clinical signs of atherosclerotic disease. Secondary prevention refers to those who have had a myocardial infarction or angina or intermittent claudication (Reid et al, 2001).

Scientific evidence supporting a causal relationship between elevated serum cholesterol and coronary heart disease is well established.

Excess cholesterol can be deposited in arterial walls, leading to atherosclerosis. Progressive atherosclerosis of arteries leads to the formation of atherosclerotic plaques that cause lumen narrowing (Edmunds, 2003). These plaques may eventually erupt, leading to the formation of thrombus.

Thrombus formation increases the degree of lumen narrowing and may result in total occlusion. In the coronary arteries this may precipitate an MI. If the occlusion occurs in the cerebrovascular system (carotid arteries) it may precipitate a transient ischaemic attack (TIA) or stroke.

Lipid-lowering medication
The aim of lipid-modifying treatment is to reduce circulating levels of atherogenic lipids. Cholesterol and triglycerides are classified as lipids and are normal and vital constituents of plasma (Edmunds, 2003). Cholesterol and other lipid fractions are transported in the blood via lipoproteins (albumin and globulins).

Lipoproteins are composed of fats and proteins and are produced in the liver. The concentration of blood lipoproteins is determined partly by dietary intake and partly by metabolic processes in the body (Downie et al, 2003).

Lipoproteins have a core of cholesterol and triglycerides and an outer shell of phospholipids and protein. There are five classifications:

- Chylomicrons

- Very low-density lipoproteins (VLDLs)

- Intermediate-density lipoproteins (IDLs)

- Low-density lipoproteins (LDLs)

- High-density lipoproteins (HDLs).

Chylomicrons and VLDLs are considered triglyceride-rich lipoproteins, whereas LDLs and HDLs are considered cholesterol-rich lipoproteins (Reid et al, 2001). The IDLs have a balanced mix of cholesterol, triglycerides and protein. LDLs are often referred to as 'bad' cholesterol and the HDLs as 'good' cholesterol. This is because of their opposite functions:

- LDLs transport cholesterol from the liver to the peripheral tissues

- HDLs remove cholesterol from the periphery and transport it back to the liver where it undergoes further metabolism.

As such, high levels of HDL are seen as beneficial and protecting against developing coronary heart disease (CHD), with an inverse correlation with CHD (Edmunds, 2003).

Disorders of lipid metabolism occur as primary conditions that may be familial or polygenic in origin or secondary to an underlying disease state or drug treatment (see Box).

The different disorders are characterised by high plasma concentrations of cholesterol or triglycerides or both. In familial hypercholesterolaemia and polygenic disorders raised levels of LDLs are found, whereas in secondary lipid disorders triglycerides levels are raised. Statins are the drugs of first choice for treating hypercholesterolaemia and fibrates for hypertriglyceridaemia (BMA/RPSGB, 2004).

Statins are administered orally as tablets or capsules and absorbed from the gastrointestinal tract. The drug starts to break down in the stomach and passes with gastric emptying into the intestine. As its concentration is higher in the intestine, the drug diffuses across the intestine wall into the bloodstream. It is then transported to the liver where it undergoes phase 1 metabolism. This involves chemical reactions such as oxidation, reduction and hydrolysis.

As these drugs undergo a marked first-pass effect in the liver, that is where most effect is seen. Statins are excreted in the faeces and urine. Peak effect is usually within two to four weeks.

The half-life of statins is between one to three hours. However, the duration of enzyme inhibition appears to be longer. This allows for administration once a day, and because cholesterol biosynthesis largely takes place at night (Feely, 1994) they should be taken before bedtime.

Statins inhibit the action of the rate-limiting enzyme 3-hydroxy-3-methoxygluteryl coenzyme A (HMG CoA), a necessary component of cholesterol synthesis in the liver (Edmunds, 2003).

HMG-CoA reductase inhibitors (statins) block HMG reductase from completing the synthesis of cholesterol (Hopkins et al, 1999). A reduction in cholesterol synthesis increases the availability of active low-density lipoprotein (LDL) receptors, resulting in an increase in the uptake of and removal of cholesterol from the circulation (Hopkins et al, 1999).

There is a subsequent reduction in serum cholesterol and a decrease in serum LDLs and, in some cases, a slight increase in serum high-density lipoproteins (HDL) levels.

Contraindications/adverse effects
Most statins are chemical modifications of compounds produced by fungi (Karch, 2003) and patients allergic to fungal products should avoid them. They are contraindicated in patients with active liver disease or high alcohol intake, and should be avoided in pregnancy and breastfeeding. Caution is needed in patients with impaired endocrine function, due to potential alteration in steroid hormone formation (Karch, 2003).

Statins appear well-tolerated. However, long-term safety evaluation has yet to be confirmed (Reid et al, 2001). Gastrointestinal (GI), central nervous system (CNS), hepatic and muscular effects have been reported (Karch, 2003).

Familial hypercholesterolaemia

Autosomonal dominant condition

characterised by a lack of (homozygotes) or reduction (heterozygotes) in LDL receptors

Polygenetic lipid disorder

Caused by a variety of factors, including non-specific genetic predisposition, dietary factors and physical inactivity. It is the most common lipid disorder in westernised populations

Secondary lipid disorders

Caused by underlying conditions such as hypothyroidism, diabetes mellitus or drugs such as diuretics and beta blockers.

Source: Reid et al, 2001






BMA/RPSGB. (2004) British National Formulary 47. London: British Medical Association/Royal Pharmaceutical Society of Great Britain. (accessed June 2004).

Downie, G., Mackenzie, J., Williams, A. (2003)Pharmacology and Medicines Management for Nurses (3rd edn). London: Churchill Livingstone.

Edmunds, W.E. (2003)Introduction to Clinical Pharmacology (4th edn). Hong Kong: Mosby.

Feely, J. (1994)New Drugs (3rd edn). London: BMJ Publishing.

Hopkins, S.J., Kelly, J.C. (1999)Drugs and Pharmacology for Nurses (13th edn). London: Churchill Livingstone.

Karch, A.M. (2003)Focus on Pharmacology (2nd edn). Philadelphia, PA: Lipincott, Williams and Wilkins.

Reid, J.L., Rubin, P.C., Whiting, B. (2001)Lecture Notes on Clinical Pharmacology (6th edn). Oxford: Blackwell Science.

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