Atorvastatin chemical structure
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Atorvastatin


Atorvastatin (INN) (IPA: ) is a member of the drug class known as statins, used for lowering cholesterol and thereby preventing cardiovascular disease. Atorvastatin inhibits a rate-determining enzyme located in hepatic tissue used in cholesterol synthesis, which lowers the amount of cholesterol produced. This also has the effect of lowering the total amount of LDL cholesterol. more...

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Unlike most statins, atorvastatin is a completely synthetic compound.

Atorvastatin is currently marketed by the pharmaceutical company Pfizer as Lipitor®. In some countries it may also be known as: Sortis®, Torvast®, Totalip®, or Xarator®. With 2004 sales of US$10.9 billion, it is the best selling drug in the world.

Clinical use

Indications

Atorvastatin is indicated as an adjunct to diet for the treatment of dyslipidaemia, specifically hypercholesterolaemia. It has also been used in the treatment of mixed hyperlipidaemia. (Rossi, 2006)

Available forms

Atorvastatin is marketed as atorvastatin calcium under the trade name Lipitor, in tablets (10, 20, 40 or 80 mg) for oral administration. Tablets are white, elliptical, and film coated.

Adverse effects

Common adverse drug reactions (ADRs) associated with atorvastatin therapy include: myalgia, mild transient gastrointestinal symptoms, elevated hepatic transaminase concentrations, headache, insomnia, and/or dizziness. (Rossi, 2006)

Myopathy and rhabdomyolysis are rare, but serious, dose-related ADRs associated with statin therapy. Risk is increased in patients with renal impairment, serious concurrent illness; and/or concomitant use of drugs which inhibit CYP3A4. (Rossi, 2006)

Mechanism of action

Atorvastatin is a competitive inhibitor of HMG-CoA reductase. This enzyme catalyzes the reduction of 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, which is the rate limiting step in hepatic cholesterol synthesis.

Because cholesterol synthesis decreases, hepatic cells increase the number of LDL receptors on the surface of the cells, which increase the amount of LDL uptake by the hepatic cells, and decreases the amount of LDL in the blood.

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CARDS study demonstrates benefits of atorvastatin
From Diabetes and Primary Care, 9/22/04

Lipitor significantly reduces heart attacks and strokes in patients with diabetes, according to data presented at this year's meeting of the American Diabetes Association in Orlando. In the Collaborative Atorvastatin Diabetes Study (CARDS), which involved more than 2800 patients with type 2 diabetes, no history of heart disease, and relatively low levels of cholesterol, patients who took Lipitor had a 37% reduction in major CV events.

In addition, 48% fewer Lipitor-treated patients experienced strokes compared with those who received placebo, and the overall mortality rate for Lipitor patients was 27% lower than for those on placebo. 'This important study has demonstrated that lowering cholesterol with atorvastatin in patients with diabetes (even those whose LDL levels were relatively low) will result in a dramatic cardiovascular benefit,' said Professor Helen Colhoun, CARDS co-principal investigator, University College Dublin.

'The benefit was so great that the trial had to be terminated early. CARDS demonstrates that statin therapy can be of great benefit to the vast majority of diabetes patients, and that atorvastatin is highly effective and safe.'

COPYRIGHT 2004 S.B. Communications
COPYRIGHT 2004 Gale Group

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