Statins: much more than cholesterol reduction

Lovastatin was the first statin to be approved in 1987 by the US Food and Drug Administration (FDA). Its approval marked a giant leap forward not only in the treatment of hypercholestolemia, but especially in the primary and secondary prevention of atherosclerosis. However, the approval of lovastatin and the fact that the statin market is growing literally by the minute have also initiated a race among pharmaceutical companies to develop the next blockbuster drug. Whilst the first statins were still natural substances, the latest additions to the class were in fact synthetic products. Indeed, lovastatin is a natural product derived from the mold Aspergillus terreus, and simvastatin and pravastatin are likewise products of fungal fermentation. Fluvastatin and atorvastatin are synthetic statins, and the latter has been viewed as the most potent in its class for almost 7 years. The approval of rosuvastatin in August 2003 marked the next rung in climbing the ladder towards the strongest statin. However, its approval also triggered a heated debate about the marketing strategy of the drug and the fact that the FDA denied approval of the 80 mg dose [1].
Since 1987, statins have become something like lifestyle drugs, and in May 2004, British authorities even decided to make the 10 mg dose of simvastatin available on an over-the-counter (OTC) basis, i.e. without a prescription being necessary [2]. At that time, the UK authorities said that the balance of benefit to risk was “overwhelmingly positive” and that the move should reduce heart disease. This step prompted the Lancet to point out that the British public was now being made “guinea pigs in this large-scale OTC experiment” [3], because data on OTC statins for the primary prevention of heart disease are missing, as are data on compliance. Truly, caution in the use of statins is still warranted. Although statins are generally considered safe, rhabdomyolysis may occur as a very rare side effect. Indeed, cerivastatin was withdrawn from the market in 2001 as it was implicated in a total of 52 deaths worldwide [4].
The primary effect of statin use is the lowering of serum cholsterol levels, and each doubling of the dose of a statin is said to decrease serum cholesterol levels by another 7% [5]. However, statins also possess a large number of effects beyond mere cholesterol reduction. These effects are called “pleiotropic effects”, and we have only just...


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