The Heart Protection Study Collective Group cost effectiveness findings published on 10 Nov 2006 in the British Medical Journal grossly misrepresented the costs of statin treatment in terms of myopathic consequences.
From the beginning of statin use the drug company prediction of likelihood of muscle problems has been grossly optimistic. Instead of the two per cent figure originally promised, the true incidence of muscle problems proves to be much closer to 20% and even than may be an underestimate according to Draeger's group.
In the Journal of Pathology 210: 94-102, 2006, Draeger A and others of the University of Bern, Switzerland reported that statin therapy induces ultrastructural damage in skeletal muscle in almost every patient and often without myalgia. Draeger's group did skeletal muscle biopsies from statin treated and non-statin treated patients and examined them using electron microscopy and biochemical approaches. They reported clear evidence of skeletal muscle damage in statin treated patients despite their being asymptomatic.
Although the degree of overall damage was minimal, it was the characteristic pattern of damage, including rupture of critical structures that caught the attention of the investigators. These findings support the hypothesis that statin induced cholesterol lowering per se contributes to myocyte damage and suggests further that it is the specific lipid / protein organs of the skeletal muscle itself that renders it particularly vulnerable.
Another previously unsuspected mechanism for muscle damage is selenium inhibition. Mooseman and Behl postulate that this type of myopathy is due to direct interference of the isopentyl step of the mevalonate pathway as a consequence of the almost inevitable statin induced fall in available selenoproteins. The substrate for this reaction, isopentanyl pyrophosphate IPP, is a direct metabolite of mevalonate.
All statins inhibit this function. The resulting clinical picture of statin associated myopathy includes a non-uniform pattern of muscle aches and pains, weakness and tenderness with easy fatigability. It can vary from mild to very severe, or even be disabling. This pattern of signs and symptoms is very similar clinically and pathologically to those induced by severe selenium (selenoprotein) deficiency, supporting their hypothesis.
An additional factor is that some patients may have a genetic susceptibility to statin use. Special genetic susceptibility may explain not only much of our statin associated rhabdomyolysis but also the curious pattern of persistent myopathy, often following only a short course of statins. Since susceptibility testing of this type is not yet available, there is no way to identify these susceptibles until the damage is done.
One of these genetic determined enzymatic conditions is carnitine palmitoyl transferase (CPT) deficiency. The enzymes involved are found on different membranes of our mitochondria, those busy factories within each of our cells responsible for the production of our (ATP) energy. Produced in each of our body's million's of cells, mitochondrial ATP is our body's sole source of energy. CPT enzymes work together with Coenzyme Q10 in the process of transport of fatty acids into our mitochondria and their ultimate conversion into fuel. Deficiency of this class of enzymes is characterized by unusual muscle pain and stiffness after exercise or work.
Campbell recently has described five cases of polymyositis due to statin drugs, which appear to be due to causes different from the usual, more common types of muscle damage. Cortisone therapy was required in all five cases raising the possibility of statin pro-inflammatory effects in some people. Campbell proposes a previously unsuspected effect of statins on our muscle cell lipid / protein "rafts", recently described, that results in a tendency to apoptosis (cell death and disintegration). It is these remnants of apoptosis that incite the autoimmune reaction and cause the inflammatory response.
Thus, five new mechanisms of statin damage to muscles have been reported just in the past two years and are added to my original hypothesis of the primary cause being statin induced CoQ10 deficiency with loss of cell wall integrity. Two of these (cholesterol lowering per se and selenoprotein inhibition) involve mechanisms that seem to be "across the board" and one (genetic susceptibility) involves a process that cannot be identified ahead of time without special testing.
Such observations strongly argue against excessively liberal statin use and especially over the counter distribution of such drugs. It is one thing when a drug causes a few aches and pains and something entirely different when the aches and pains may be permanent and disabling or, as in rhabdomyolysis, even fatal.
Dr. Beatrice Golomb of the NIH funded UCSD statin study reports a myopathy rate among her thousands of case reports as close to 40% a figure very close to that of my own statin side effect repository with its several thousand case reports.
The people who made this cost effectiveness study have not done their homework. Cost means far more than money when used in these determinations. If, on the other hand, the authors intended it to be just money, then their assessment is worthless.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor