(from 1997 through May 15, 2012)
by Duane Graveline, M.D., MPH
FDA has opened the shelves of MedWatch to those of us wishing to review for ourselves the status of statin adverse drug reports (ADRs). This has been all the more imperative since FDA has been extremely reluctant to report side effect data on the statin class of drugs.
I was last able to access MedWatch data in 2006. Following that, in the beginning of 2007, my access to MedWatch data was denied despite legal pressure from my lawyers. Even 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 ADRs using the “find” mechanism on my PC. This was necessary, I was told, since the appropriate software for reading MedWatch data was available only to FDA and drug company officials. The rest of us had to be content with the time-honored and accurate but painfully slow process of counting each case one by one using the search mechanism on our PC.
What prompted me to do this personal search of what most would agree is FDA’s business is the almost total lack of awareness of most doctors of statin-associated cognitive dysfunction, emotional and behavioral disorders and cases of disabling neuromuscular degeneration. Clearly our doctors have not been informed about most of these reactions, yet I know from the 20,000 emails I have received through my website (www.spacedoc.com) that many thousands of MedWatch reports have been submitted. In many cases I have been instrumental in helping distraught victims make their FDA report. What is wrong with our ADR reporting system, I wondered? I used the Lipitor data for this report. It is important to remember that all statins are reductase inhibitors blocking a single reductase step in the synthesis of cholesterol, so what is true for one is generally true for all statins. The only real variable is strength.
Because of my personal cognitive experience with this drug, transient global amnesia (TGA) was the first search term I entered. TGA is the abrupt (in seconds) loss of the ability to formulate new memory, usually associated with retrograde memory loss that extends weeks, months, years, or even decades into the past. Along with memory goes any flight training you might have received. You may no longer recognize the cockpit! I lost my entire medical training for a bizarre 12 hours when I believed myself to be 13 years old.
Not unexpectedly, out popped 1,302 case reports for TGA in the MedWatch files. Adding the search term “memory impairment” yielded me another 663 cases. This total of 1,965 reports of serious cognitive dysfunction associated with the use of Lipitor seemed to fit quite well with the total numbers of such reports I now have recorded in my repository. I have generally recommended that victims do online MedWatch reporting and had helped more than a few to do just that.
A word of caution concerning gross under-reporting deserves to be mentioned here. First of all, anyone experienced with the operation of such non-mandatory reporting systems as MedWatch fully realize that they are lucky if one percent of the actual events get reported. So for every 100 cases of memory loss only 1 or 2 will ever be reported. That is the nature of self-reporting systems. Additionally, only the more severe forms of cognitive dysfunction get reported – the transient global amnesia and severe memory loss. More minor forms of cognitive loss such as confusion, disorientation or unusual forgetfulness are never included, so we should not expect to find them in the database. Then we have the category of short-term cognitive loss with durations measured in seconds and minutes. By their very nature these will rarely be recognized even by the victim, and yet they might be so critical to a pilot, the crew and passengers. The passage of time is too short for recognition, yet special studies have revealed just how common these brief lapses are.
Despite the fact that in February, 2012, FDA announced cognitive dysfunction as a major side effect of statin drugs for the first time, the agency immensely under-played its seriousness. At no time did the report even mention transient global amnesia, although the past decade has seen an epidemic of this once rare condition. The inability to formulate new memory is bad enough, but for pilots the retrograde loss is especially serious, because along with decades of past memories whatever training you might have had then disappears. FDA focused instead on the possibility that periods of confusion and disorientation might occur. The implication was that these 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 transient global amnesia, especially in a single pilot aircraft. One does not have to be a pilot to be concerned about this – anyone whose occupation requires 24/7 vigilance should be concerned. These could include a school bus driver, heavy equipment operator or even, hopefully not, our Chief of State.
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, the next search term I entered was rhabdomyolysis, an especially serious form of muscle damage with a fatality rate of 10%. You may recall that it was rhabdomyolysis that led to the Baycol withdrawal from the market. Some 60 deaths in the year 2004 made it untenable for Bayer to continue selling Baycol. Death in these cases is due to the blockage of renal tubules by the muscle cell fragments from ruptured muscle cell membranes and been carried to the kidney by the circulation.
I counted 2,731 MedWatch reports of rhabdomyolysis. With the case fatality rate being 10%, the use of Lipitor has presumably resulted in 273 deaths up to now. Removing Baycol from the market in 2004 did not even slow down the loss of lives from rhabdomyolysis. Lipitor quickly took up the slack and similar rhabdomyolysis death rates are occurring from Zocor, Crestor and the others. Each year Lipitor accounts for slightly more than 20 deaths from this cause. Applying additional search terms bearing on the muscular system, I found 1325 reports of “myalgia” and 494 reports of “musculoskeletal stiffness”.
Applying the search term “renal failure” gave me 2,240 responses, comparing favorably with the 2731 MedWatch reports of rhabdomyolysis cases, knowing that many, if not most, of these would be accompanied by varying degrees of renal involvement.
My response to use of the search term “neuropathy” was 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 now deserve to be called permanent. Using the term “Guillain-Barre syndrome” 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. This figure better reflects the statin neuropathy load.
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 always has been a 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 diagnosis list, I used it as a search term, reporting 842 liver function abnormalities in addition to my 2,102 hepatitis cases for a grand total of 2,944.
Since Ralph Edwards of the World Health Organization detected the unexpected association of ALS with statin use by using the 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 walker took place the following day.
The Peoples Pharmacy website carries an unexpected gold mine of ALS incidence data in the following link https://www.peoplespharmacy.com/2009/07/31/statins-and-als/ Please check out this resource. Joe Graedon started this link in 2007. In it he has invited anyone struck down by statins with symptoms suggestive of ALS (Lou Gehrig’s Disease) to comment on their status for the benefit of others. The last time I dug for gold here I was quite certain I had found at least 300 solid cases of ALS with hundreds of others who still might go in that direction since, as many of you understand, it sometimes takes years for ALS to unmask itself. There is no solid test.
Relevant to diabetes, it is now generally accepted that the incidence rate of new diabetes in statin users is close to 12% – an amazing user penalty 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 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 as to 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.” With a total of 3,030 cardiac events in a group already on statins, I wonder just how much protection is being offered. Use of the search term “cerebrovascular accident” (stroke) yielded 1,562 reports, with another 159 inferred by the use of the search term “aphasia.”
FDA has a first rate monitoring system but it is grossly deficient for reporting findings back to the medical community. The average primary care physician in our country today, knowing that only a minority of patient problems get reported to 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 prescriptions for statin use.
From my 23 years of experience as a primary care doctor, I would say that any doctor attempting to practice medicine without full information on adverse reactions is liable for malpractice. Only with this information can proper, informed judgments for treatment plans be made. It pains me to see my colleagues being maneuvered into this position.
Duane Graveline MD MPH
Author: Lipitor, Thief of Memory and Statin Drugs Side Effects
Dr. Duane E. Graveline was a family doctor, aerospace medical research scientist, USAF flight surgeon and NASA astronaut. Dr. Graveline interned at the famed Walter Reed Army hospital during the time our space pioneers were just beginning to study the medical effects of space flight. He became a flight surgeon and did space medical research on zero gravity deconditioning. He held a unique position as medical analyst of the Soviet bioastronautics program, NASA flight controller and finally, in 1965, was selected as a NASA scientist astronaut. Dr. Graveline still is affiliated with the space program as consultant to the special cosmic radiation hazards to man of “return to the moon and on to Mars.”
You can listen to Dr. Graveline tell his story on our radio show.