By Duane Graveline, MD, MPH
I was last able to access MedWatch data in 2006. The process had not been easy for it meant I had to tackle the immense challenge of reviewing manually some 64,000 Lipitor® Adverse Drug Reports (ADRs) using "find" on my computer.
What prompted me to do this personal search of what most would agree is the FDA's business, is the almost total lack of awareness by doctors of statin associated cognitive dysfunction, emotional and behavioral disorders and cases of disabling neuro-muscular degeneration. Clearly doctors have not been informed.
Yet I know of the many thousands of MedWatch reports that have been submitted. In some cases I have been instrumental in helping distraught victims make their MedWatch report.
Based upon my personal cognitive experience with this drug, amnesia was the first search term I entered. Not unexpectedly, out popped 1,302 case reports for amnesia in the MedWatch files. Adding the search term "memory impairment" added another 663 cases. This gave a total of 1965 reports of serious cognitive dysfunction associated with the use of Lipitor.
A word of caution concerning gross under-reporting deserves to be mentioned here. First of all, anyone experienced with the operation of such optional reporting systems as MedWatch fully realize that the results are but an approximation of the actual numbers. Estimates for reporting of adverse drug reactions (ADRs) range from 1% to 10% meaning that the actual number of adverse reactions could be ten to a hundred times those reported to MedWatch.
Additionally, only the more severe forms of cognitive dysfunction get reported-the transient global amnesia and severe memory loss cases. Rarely included, and therefore expected to be missed, are the more minor forms of cognitive loss such as confusion and disorientation and unusual forgetfulness.
Then we have the category of short term cognitive loss with durations measured in seconds and minutes that by their very nature will rarely be recognized even by the victim, say nothing of an observer, yet might be so critical to a pilot. The passage of time is too short for recognition yet special studies have revealed just how common they can be.
Despite the fact that in February, 2012 the FDA for the first time announced cognitive dysfunction as a major side effect of statin drugs, they immensely under-played its seriousness. At no time did they even mention transient global amnesia; a strange form of completely incapacitating amnesia in which the victim abruptly, without the slightest warning, loses the ability to formulate new memory, accompanied by retrograde loss of memory for decades into their past.
The past decade has seen a big increase in reports of this once rare condition. They instead mentioned some transient episodes of confusion and disorientation might occur that usually were mild and passed with no complications. Never a word was said about the possibility of a military or civilian commercial pilot suddenly encountering this form of amnesia with retrograde loss of their flight training.
It is not only pilots that need to worry. This concern applies to anyone whose occupation requires extra vigilance including professional drivers, heavy equipment operators, surgeons, military personnel, etc.
Applying additional cognitive search terms gave me 222 reports of "dementia," 523 case reports of "disorientation" and 602 reports of "confusional state." I next searched among words that might reflect the curious effects of statin drugs on emotion and behavior now being reported. I found 347 reports using the search terms "aggressiveness," "paranoia" and "irritability" commonly reported in statin users. Use of the search term "depression" yielded 1,142 reports of which 118 expressed "suicidal ideation."
Since it also was in February, 2012 that FDA first mentioned the persistent seriousness of rhabdomyolysis, that was the next search term I entered. Rhabdomyolysis is an especially serious form of muscle damage with a fatality rate of 10%. You may recall that it was rhabdomyolysis that brought down cerivastatin (Baycol) with some 60 deaths in the year 2004 causing Bayer to remove it from the market.
Deaths in these cases are due to kidney failure caused by the blockage of renal tubules by fragments from damaged muscle cells that have been carried to the kidneys in the bloodstream. I counted 2,731 MedWatch reports of rhabdomyolysis. Removing Baycol from the market in 2004 did not stop the statin-associated loss of lives from rhabdomyolysis. Lipitor quickly filled this void and similar rhabdomyolysis death rates can be expected from the other strong statins. I calculate that each year Lipitor accounts for more than 20 deaths from rhabdomyolysis.
Applying additional search terms bearing on the muscular system I found 1,325 reports of "myalgia" and 494 reports of "musculoskeletal stiffness." Applying the search term "renal failure" gave me 2,240 responses, comparing favorably with the 2,731 MedWatch reports of rhabdomyolysis cases, knowing that many, if not most, of these would be accompanied by varying degrees of renal involvement.
Being well aware of the great numbers of reports of peripheral neuropathy in my repository, the next term I chose was "neuropathy" which yielded 1,294 reports to MedWatch. It should be mentioned that almost all of these peripheral neuropathy reports have proven to be very resistant to traditional treatment and many now deserve to be called permanent. Using the term "Guillain-Barré syndrome"-a disorder affecting the peripheral nervous system-gave 98 reports, and prompted by hundreds of case reports I have received complaining of leg and arm pain, the search term "pain in extremity" gave 3,498 reports.
Next I put in the search term, "hepatitis." Before I tell you the number, I first must qualify it by warning you that there are many different kinds of hepatitis. There is hepatitis A, B, C, cholestatic, autoimmune, fulminating, acute, chronic and viral, including cytomegalovirus. All of these terms are used in this compilation of Lipitor damage reports. However, the overwhelming majority of these reports said simply, "hepatitis" with no qualifier. Since hepatitis has always been a warned concern from statin use you must make up your own mind in interpreting the 2,102 total cases that resulted.
When I realized that "liver function abnormalities" also was being used in the MedWatch diagnoses list, I used it as a search term, reporting 842 liver function abnormalities in addition to the 2,102 hepatitis cases for a grand total of 2,944.
I should add here my thoughts on the way liver function test guidelines have been grossly manipulated during the statin era.
Some twenty years ago, doctors were still advised to use the guidelines that I had been accustomed to since my medical school training. Now, starting close to 1990, the time when statin use began to get seriously underway, doctors were asked to replace their usual routine of using the mean plus 2 standard deviations (SDs) with the mean plus 10 SDs to determine when an elevation of liver enzyme due to statins was significant or not.
This incredible distortion of reality was done in order that we not get too excited about 2 SDs when dealing with statins. The previous guidelines no longer applied. I am still trying to figure out how the clinical pathologists got away with that. It made no sense then and much less sense now. Inflammation is inflammation. When dealing with statins we have been asked to accept small amounts of inflammation as normal.
Since the unexpected association of amyotrophic lateral sclerosis (ALS) with statin use was reported by Ralph Edwards of the World Health Organization using their VigiBase® data, my next investigation of Lipitor MedWatch data was for search terms that might give a measure of ALS occurrence. "Unusual weakness" turned up 2,516 case reports, "balance disorders" gave 596 responses and "coordination abnormalities" gave 195 responses.
Since I have this condition I can speak with authority on the subject of balance disorders. A kindly neighbor lady was so concerned on seeing me walk by her home she offered to drive me the rest of the way. Until that moment I was unaware of the effect of my walking on the public eye. Clearly this "Good Samaritan" sensed me as disabled. My transition to a walker frame took place the following day.
More on ALS and statins
Relevant to diabetes, in a recent article in the NEJM http://www.nejm.org/doi/full/10.1056/NEJMp1203020 a meta-analysis of six statin trials is referenced that revealed a 13% increase in the relative risk of new-onset diabetes in those taking a statin. The FDA also added an increased risk of developing Type 2 diabetes to their February 2012 warnings-an amazing side effect for a medicine that is supposed to diminish the risk of cardiovascular disease. I used the search term "pancreatitis" to see how much of this diabetes might reflect organ damage. I found 604 reports of pancreatitis.
I see this as part of a whole body process of mitochondrial DNA damage aggravated by the use of statins. Even on our good days, mitochondrial mutations occur by the tens of thousands leading to progressive mitochondrial loss followed in time by cell loss and finally, with sufficient time, organ damage in the well known process of aging.
All of this is the inevitable consequence of normal metabolic activity. It is theft of electrons from adjacent tissues, including DNA strands, that causes the damage. CoQ10 plays a major role not only in energy formation via electron transfer but also anti-oxidation, minimizing buildup of oxidizing byproducts of metabolism and slowing down DNA damage. Via inhibition of CoQ10, statins play a major role in what amounts to enhancement of the aging process.
Applying the search term cancer (of all kinds) gave me 1,642 official reports to MedWatch of which 422 were reported as breast cancer. I next tried the search term "cardiac failure" and turned up 720 reports. CoQ10 inhibition is felt to be the major contributor to this condition. My next search was "myocardial infarction"-out of curiosity-to see how many might there be in a group already on Lipitor. The figure was 2,520-another attention getter, especially when I got 610 additional reports using the search term "coronary artery occlusion."
When you get a total of 3,030 cardiac events in a group already on statins you are justified in wondering just how much protection is being offered? Use of the search term "cerebrovascular accident" (a stroke) yielded 1,562 reports with another 159 inferred by the use of the search term "aphasia."
My last search focused on tendon complications. I found 436 from Lipitor over the time period of this report. This relatively obscure finding is based upon the role of cholesterol in tendon and ligament function. Most orthopedic surgeons are well aware of this relationship.
The FDA has a first rate monitoring system but a grossly deficient one for reporting findings back to the medical community. The average primary care physician in the U.S. today, knowing that perhaps only 10% of patient problems get reported to the FDA, would be startled to see these figures, especially the ones for cognitive dysfunction, neuropathy, rhabdomyolysis, depression, neuropathy and hepatitis. These are the people who write the prescriptions for statin use.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor