Statin

The statins form a class of hypolipidemic agents. They are used as pharmaceuticals to lower cholesterol levels in patients at risk for cardiovascular disease because of hypercholesterolemia.

Members

The statins are (brand names in countries other than the US can be different):

• atorvastatin (Lipitor®)
• fluvastatin (Lescol®)
• lovastatin (Mevacor®, Altocor®, not marketed in the UK)
• pravastatin (Pravachol®, Selektine®, Lipostat®)
• rosuvastatin (Crestor®)
• simvastatin (Zocor®)
• cerivastatin (Lipobay®, Baycol®) - marketing discontinued in 2001 by the manufacturer (Bayer) due to serious side-effects, especially when used in combination with fibrates.

Uses

The drugs are the most potent cholesterol lowering agents (LDL-cholesterol), however, they are less effective than the fibrates in reducing triglycerides and raising HDL-cholesterol. The statins play an important role in primary and secondary prevention of ischaemic heart disease and myocardial infarct.

There is ongoing research for other actions of statins apart from lipid-lowering for instance - anti-inflammatory, anti-dementive or anti-neoplastic.

Pharmacology

Groups

There are two groups of statins:

• Fermentation-derived: lovastatin, simvastatin and pravastatin
• Synthetic: fluvastatin, atorvastatin, cerivastatin and rosuvastatin

Of the groups, the former appears to be more effective in reducing LDL, but there is no clear explanation behind this phenomenon.

Mode of action

Statins act by competitively inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, an enzyme of the HMG-CoA reductase pathway, the body's metabolic pathway for the synthesis of cholesterol.

Although statins inhibit endogenous cholesterol synthesis, their action goes further than that. By reducing intracellular cholesterol levels, liver cells upregulate expression of the LDL receptor, leading to increased clearance of Low-Density Lipoprotein from the bloodstream. This mechanism was clarified by Dr Michael S. Brown and Dr Joseph L. Goldstein, who received the Nobel Prize in Physiology or Medicine for their work in 1985.

Non-cholesterol related actions

Statins exhibit action beyond lipid-lowering activity in the prevention of atherosclerosis. There are four proposed mechanisms by which statins are thought to prevent cardiovascular disease (all are the subject of a large body of biomedical research):

1. Improving endothelial function
2. Modulate inflammatory responses
3. Maintain plaque stability
4. Prevent thrombus formation

History

Lovastatin (mevinolin, MK803), the first statin to be identified, was isolated from the mold Aspergillus terreus in the late 1970s.

See also

• Scandinavian Simvastatin Survival Study (4S)
• Heart protection study (HPS)

Reference

• Furberg CD. Natural statins and stroke risk. Circulation 1999;99:185-188. PMID