By Duane Graveline, M.D., M.P.H.
Myopathy associated with statin use has long been warned of by the drug companies to be about 2%. Recently Dr. Beatrice Golomb - Director of the University of California, San Diego ( UCSD ) statin study funded by the U.S. National Institutes of Health ( NIH ) - reported her estimates for the incidence of statin associated myopathy to be much closer to 10%.
From my own study over the past decade using a repository of reports very similar to that of Dr. Golomb I suggest that the true incidence of statin associated myopathy could be even higher than that.
In my opinion, attempting to infer muscle damage incidence from the usual large-scale clinical studies is futile. For example, in one clinical study I read of 20,000 subjects being placed on a fixed 80mg dose of a statin for 2 years with a final report that no significant adverse effects were noted.
Clearly, when the predicted drug company rates of 2% did not appear, as in this study, I have reason to dismiss the validity of the report with respect to side effect monitoring.
With respect to Medwatch data, some of the information is relevant to myopathy incidence. For example, for the statin drug Lipitor® over the period 1998 through 2006, I was jolted to discover 1592 reports of rhabdomyolysis hospitalizations.
Rhabdomyolysis can be considered to be a more robust, malignant form of myopathy but the incidence of myopathy evolving into rhabdomyolysis is far from established.
Searching Medwatch raw data using the key word "myopathy" results in 628 reports during the 1998 through 2006 time period. During that same time period 69 reports of "arthralgia", 574 reports of "myalgia", 207 reports of "musculoskeletal stiffness" and 101 reports of "musculoskeletal pain" were recorded. Search terms, "pain in extremity" gave 1799 reports and "asthenia" gave 178 reports.
Clearly myopathy can manifest in many different ways depending upon the doctor involved. It is commonly stated that only 1% of adverse reports such as myopathy might be reported to Medwatch, indicating that the search term mix of several thousand reports above most likely becomes substantially higher in real life, officially reported to the U.S. Food and Drug Administration ( FDA ).
Common sense, however, tells us that for the condition myopathy only the most serious would be brought to a doctor's attention sufficiently for him to post a report and many MDs even then would be reluctant unless the condition threatened to evolve in rhabdomyolysis. I suspect less than 10% of myopathy reported to the doctors by patients are reported on to Medwatch.
Bottom line is that Medwatch is completely inadequate for incidence reporting purposes and lacking additional information, Dr. Golomb's myopathy incidence data of 10% is the best formally derived data we have. With at least 30 million U.S. citizens said to be on statins, this 10% expected muscle pain figure becomes truly worrying when one learns that, according to Dr. Golomb, in 68% of these people the muscle pain will become permanent or even more extensive despite stopping the statin.
It was this issue of permanency of statins' adverse reactions that prompted me to investigate the possible cause. CoQ10, which is part of both structure and function of complex 1 and 2 of the mitochondrion, has been suspected for a long time to be involved but quite disconcerting was the observation that in most of these cases of permanent myopathy, neuropathy and neuromuscular degeneration, the use of CoQ10 even in very heavy dosing often accomplished nothing once the diagnosis was made.
Evidence indicates that excess oxidation is the key and once this mitochondrial damage has occurred, this damage tends to be permanent. Our daily load of metabolic free radicals are kept in nominal quantities by the anti-oxidative effects of antioxidants including CoQ10.
Enter statin use with its inhibition of CoQ10 synthesis secondary to mevalonate blockade. Now our daily load of oxidizing free radicals is largely unchecked, exerting its full impact on the adjacent mitochondria. Damage is immediate and permanent.
Had CoQ10 been added before taking a statin, perhaps this excess oxidative damage could have been lessened or even prevented, but now further CoQ10 effect will accomplish nothing for the damage is done.
You have heard the expression, "locking the barn door after the horse has been stolen". This is the same thing. For those living in Canada, they would have been strongly advised by the Canadian Government to take supplemental CoQ10 before starting statin treatment but here in the United States no mention is made of supplementing statin use with CoQ10. The result has been thousands of victims with statin induced permanent mitochondrial damage.
If the mitochondria involved are in nerve tissue, the result is peripheral neuropathy. If in muscle, the result is varying degrees of myopathy. If in brain or heart the result is amnesia or other cognitive loss or congestive heart failure or it is possible to have all four conditions. The damage depends upon which tissue has the greatest damage.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor