In this issue: the statins
While waiting in the queue in Boots to collect your holiday snaps, you may have noticed the exhortation to have your blood cholesterol level checked - free of charge! Beneath this apparently altruistic gesture lies a hidden benefit for pharmacies. One of the statins (Zocor or simvastatin) is now available over-the-counter without a prescription. So what are statins and what do they do?
The story begins in Tokyo in the 1970s, where Japanese researchers at Sankyo were screening moulds to see if they produced compounds that would inhibit the production of cholesterol, a known risk factor for the development of coronary artery disease. After investigating ca 8000 strains of moulds, they isolated a natural product that they called mevastatin from the mould Penicillium citrinum. In the same year, chemists at Beechams in the UK isolated the same compound from another mould, Penicillium brevicompactum. Both groups showed that this natural product reduced the production of cholesterol in the liver by inhibiting a key enzyme that converted hydroxymethylglutaryl coenzyme A (HMG CoA) into mevalonic acid, the vital intermediate for the biosynthesis of cholesterol. HMG CoA has a similar structure to mevastatin (1), and it is because of this that the enzyme is fooled into thinking that the latter is the substrate for its chemical conversion into mevalonic acid.
Eventual success
Mevastatin never entered clinical use because it prevented production of cholesterol in the lens of the eye and also the adrenals, thus causing unacceptable complications. However, three years later, the Japanese researchers isolated lovastatin (2) while chemists at Merck in the US isolated the same natural product and then introduced a methyl group into lovastatin, thus making the first semi-synthetic statin, simvastatin (3). Both of these statins are specific inhibitors of cholesterol biosynthesis in the liver. Simvastatin was the first statin to be introduced for use in the UK for patients with severe hypercholesterolaemia - the presence of high levels of cholesterol in the blood.
The success of these early statins and others since introduced have contributed enormously to the reduction in deaths owing to heart attack and stroke over the past 20 years. In the last five years alone, the death rate has been reduced in the UK by 23 per cent thanks to the six approved statins that include lovastatin (Mevacor), simvastatin (Zocor), atorvastatin (Lipitor), and rosuvastatin (Crestor). These are being used by 1.8 million patients in the UK at a cost to the NHS of around £750 million per annum - the largest contribution to the NHS drugs' bill. This explains the excitement about a switch to over-the-counter sales, especially for those people at mild to moderate risk because their cholesterol levels are only slightly elevated. Think of the advantages: lives will be saved, the Government will save money, pharmacies will have more customers, and for the drug companies these are the best of all drugs - they are safe, effective, cause few side effects, and patients must take them for the rest of their lives.
