Almighty: The powerful makers, promoters and distributors of the stronger statin drugs.
Candide: Innocent and skeptical doctors and their patients.
Watchover: FDA's medwatch program.
Shield: Pharmaceutical companies adverse drug event reporting program.
PDR: Physician Desk reference of drug use and effects.
Almighty: "Our wise counselors tell us the time has come to promote the use of our wonderful statin drugs to an even wider audience. Perhaps all blood relatives and even children now should be included in our primary prevention efforts. It is for the common good that we seek this."
Almighty: "The side effects are but a nuisance - a minor and almost negligible factor with this fine product. Think of the thousands of lives we are saving. Is there any real doubt as to the common good of our efforts?"
Candide: Over fifty deaths occurred among users of your fine statin drug, Baycol, only recently removed from the market. I do not consider this minor or negligible nor do you, I am sure. I am very concerned about these deaths. Why did there have to be in excess of fifty tragic events before action was taken? Would not ten have been sufficient, or even one? What say you to this?"
Almighty: "This was a failure of your government's Watchover program, not ours. We have been scrupulous in our adherance to governmental guideline`s. Deficiencies such as you describe are attributable solely to guideline inadequacies. Certainly our vigilant Shield program gave us no warning.
Candide: "May I say that your Shield program in its present form may be more protective for you than the public? In its present form your so called drug hotline is nothing more than a barrier, prohibiting, rather than encouraging, communication with those among you serving as medical advisors. Manned by robots only superficially resembling life forms their response to an earnest request to talk with someone with authority is considerably less than satisfying."
Almighty: "Your critical statement is completely unjust. Think of the good we are doing from the extensive use of our statin products and the lives we are saving? Millions of people now are taking our products. Most assuredly our sentiments are for the health of the public."
Candide: "I appreciate the saving of lives but at what cost? On the subject of cost may I state as an aside that the astronomical financial rewards you have derived thus far from your drugs already have vastly exceeded your developmental costs yet we still must pay the same exorbitant price we paid years ago. I sense greed here but the costs I was referring to are the costs of pain and suffering as well as deaths in some users of your wonder drugs. Is this really necessary?"
Candide: "What you say is generally true with the possible exception of your Baycol drug but because of the vast numbers of people now taking statin drugs even a one in a thousand incidence of a problem, low by any reckoning, becomes one thousand when a million people are taking this drug. Total Global Amnesia, once so rare that most physicians have never seen a case in their entire careers, is now quite common in our emergency rooms associated with simply being on a statin drug. But amnesia is only the tip of the iceberg. For every amnesia case report there are hundreds if not thousands of cases of confusion and severe memory disturbance associated with being on statin drugs."
Almighty: "Memory disturbance you say. What person over the age of fifty has not encountered memory disturbance, long before the advent of statin drugs."
Candide: "Right you are and therein lies the problem. For years patients have been interpreting deterioration of memory shortly after starting statin medications as simply coincidental presenility or the earliest harbingers of Alzheimers, never making the association that these symptoms might be a side effect of a medication their physicians have prescribed. Similarly, physicians have tended to discount patient reports for the same reasons, never suspecting the medication the drug company's detail men have been pushing could be subtly aggravating the relatively common complaint of memory problems among those over the age of fifty. This also could explain very well the failure of your Shield program to alert you that statin drugs might be causing serious cognitive problems. Neither patient nor doctor is likely to file an adverse drug report when they firmly believe they are dealing with advancing senility."
Almighty: "But we have listed these very problems in our PDRs description of possible side effects. What more can we do?"
Candide: "Could it be that your presentation of memory and amnesia in your side effect profile may be more like burying them amidst the confusing paradoxes of both agitation and lethargy, constipation and diarrhea, drowsiness and sleeplessness or both high blood pressure and low blood pressure often reported side by side as possibly related to statin use in some people. I consider presentation in this format beyond reasonable interpretation of even the most trusting and dedicated practitioner? Could we suggest that, like your adverse drug reporting system, such presentation is more for your legal protection than doctor edification?"
Almighty: "You have made your point that memory and amnesia are important in our daily lives but aren't you exaggerating things a bit. Can you relate even one case report where someone has been harmed because of poor memory attributable to our statins?"
Candide: "My inability to cite a specific instance at this point is the very same reason that your Watchover and Shield programs have failed to alert you promptly - lack of awareness among the general public and primary care physicians that cognitive side effects can result from statin drug use. So when a senior citizen goes on a two-day "walkabout" or, much worse, drives his car across three states in a whirlwind of wanderlust with absolutely no recollection when finally apprehended, rarely is the association made between his actions and his medications. One of our doctors, a senior primary care physician, who experienced a prolonged episode of total global amnesia six weeks after having been placed on Lipitor, reported that neither the emergency room doctors or the attending neurologist had the slightest awareness that their might be a relationship between this drug and his amnesia. The following year this same doctor when re-challenged by Lipitor at one-half the previous dose experienced a much longer amnesia episode shortly thereafter in which he regressed nearly to his teens with absolutely no recollection for the intervening fifty years. Again the same doctors marveled over his completely classic Total Global Amnesia while expressing strong doubts as to any possibility of a relationship with a statin drug. Incidentally this same doctor has expressed the gravest concern as to what might have happened had he been an airline pilot or a school bus driver when his statin drug abruptly took control of his life. Later he added that had he been flying his ultra-light, a common past-time for him, loss of control would have been inevitable."
Almighty: "An interesting, even amusing anecdote of no real consequence and explainable equally by other non-drug factors, which have been around long before statin drugs and you must agree that no harm resulted. Since you are unable to cite for me even one instance of harm resulting from statin drug induced transient memory loss and confusion, I rest my case as to the inherent safety of our remarkable product."
Candide: "Even though I have no actual record of physical harm you know as well as I that physical harm may well have occurred, not once but perhaps many times. Did you not just express to me your surprise and even shock at the numbers of Baycol deaths? Is anything more harmful than death? Certainly I did not know of these deaths until the time when the unfortunate drug was abruptly removed from the market. So the credibility of your Shield and FDA's Watchover programs has been seriously compromised. You might say it is lacking. Perhaps you should tell ME how much evidence of physical harm you people are sitting on, no doubt hoping it might just go away.
Almighty: "Surely you do not mean this terrible allegation? Tell me you jest? I promise you that if anyone had reported cases of this type to our Shield program, we would have been the first to react. Our product is a boon to society. The only problem of substance I see is that we are not reaching all those unfortunates who are in dire need of statin therapy. Your quibbling about your rare, relatively minor and quite harmless cognitive side effects may seriously hamper our outreach efforts."
Candide: "Again I must direct your attention back to the point we already have made. Lack of physician and patient awareness of possible relationships between cognitive side effects and the use of statin drugs almost guarantees that no instances of accident and statin drug use will be reported to you. The medical examiner or police are very satisfied with a "touch of senility" or "senior moment" causation in this climate of complete statin "safety" you have established. Rare is the examiner who would look more closely."
"Let us redirect our attention again to the subject of harm and this time view harm from a different perspective - that of psychological harm. Here I am speaking of the reports we have received from guilt ridden and thoroughly angry sons and daughters who watched their parents rapidly descend into dementia shortly after having been started on statins by their doctors who were striving only for the very best preventive care. We now know that many of these cases were not coincidental senility or Alzheimer's disease but drug induced cognitive side effects. The harm here is to the guilt-ridden relatives who now suspect the statin drug and especially to the prescribing doctor who forever will be regarded by them as inadequate at best and possibly negligent. This well-intentioned doctor may be completely unable to accept the reality that he may have been contributing to this sad state of affairs. He has been using this drug for years and only now is the cognitive issue surfacing. His ignorance of a possible relationship between his statin prescriptions and the subsequent decline in mental faculties of his patients is because you have buried this information in your PDR rather than effectively presenting it. This doctor has been wounded just as critically as the bereaved children. In light of this reality please do not say to me how "harmless" is your statin."
Almighty: "Why will you not accept that theses infrequent cases you cite are simply co-incidental, nothing else? One of our very learned colleagues in the hallowed halls of Pfizer has recently stated that, "There is a lot of evidence that statins improve memory function and no good evidence that it affects memory in a negative way." What say you to this?"
Candide: "If this man be truly learned then I would say he is ignorant of the data which now exists and which I have seen. If, on the other hand, he has seen this data and can still make that statement then he is a fool, wearing the hat of medical advisor but not qualified for it."
Almighty: "Strong words, indeed, and perhaps brash. May I ask why you feel qualified to pontificate so authoritatively on this subject?"
Candide: "I am trained, I have seen the data and I am not on your payroll. The last point is perhaps the most important - for the advice of a hireling is always confounded by secondary gain. A truly wise man always seeks independent counsel."
Almighty: "I want you to know that all of my many advisors flatly dispute the notion that statins contribute to memory problems but your words have strange appeal. Tell me more, especially about Total Global Amnesia but be warned that this condition is described in a medical encyclopedia printed long before the development of statins. Common sense would compel me to ask why you look to statins as the cause?"
Candide: "You ask a fair question and I have an answer that, in my opinion, is equally fair. When I was in my first year of medical school, Total Global Amnesia was described in my texts as a condition so rare that few physicians ever saw even one case. I was to practice medicine for nearly fifty years without encountering it. Now in this past year I have encountered a veritable flood of reports from all walks of life and across a wide spectrum of ages, all associated with statin drug use."
Almighty: "But my medical advisors tell me such reports are anecdotal and not to be considered as definitive evidence."
Candide: "Not admissible in your corporate court, therefore? I challenge your cavalier dismissal of such information. My medical professor used to say - listen carefully to the words of your patient. He is telling you the diagnosis. I would say the same to you - listen carefully to these case reports, for they are telling you a problem exists. To ignore them for no other reason than because they lack the double-blind format of standard research data is to deny they exist. Protocol appears to have blinded your advisors. None are so blind as those who will not see."
Almighty: "I wish to state for the record that we strive to do what is best for our public, which includes common citizens as well as our many shareholders. That we have saved thousands from premature strokes and heart attacks through the use of statins is accepted throughout the medical community. That a healthy pharmaceutical industry is good for society in general is also accepted. Now suppose you tell me of some of these case reports so that I may judge for myself how heavily they tilt the scale of justice.'
Candide: " I agree that you undoubtedly have prolonged the lives of thousands of individuals who tolerate the statin class of drugs. My concern quite obviously is not with your successes but with the large numbers of patients having intolerable and harmful side effects. How much a price must society pay for your successes? You pointedly left unsaid that your statin drug is now a multi-billion dollar industry. May I suggest these profit dollars and homage to your shareholders weigh heavily on your scale of justice? I never trust the words of those who would profit from them nor could I ever trust judgments you make of your statin "cash cow" but I will cite some of these cases if it pleases you."
"A wonderfully bright and witty lady, recently retired to her rural home after a rewarding career as top-level administrative secretary, awoke one morning to view new snowfall and the realization that she must go outside to split some wood for her kitchen stove. One can imagine her surprise when after opening the kitchen door she noted wood already split and piled somewhat haphazardly on her porch. Also evident were numerous footprints in the new snow suggesting to her that the nice young man next door must have done her the favor of splitting her wood, although this had not happened before. After collecting a few pieces of wood for her stove and returning to her kitchen she noted a partially consumed plate of food on the table. Someone had entered her home, she thought, and helped himself to food from her refrigerator. Now alarmed and confused, she naturally suspected an intruder, prompting her to do a thorough search of her home. Finding no one and about to call the police she took another look at her porch. It was then she noted that the pattern of all the prints matched the pattern on the sole of her winter boots. Realization dawned -she was both the well-intentioned neighbor and hungry intruder. Her anxiety over this alien amnesia lingered for weeks despite reassurances from the emergency room doctors that all her tests were negative and that her symptoms possibly were due to Lipitor, her new statin drug, which she stopped immediately. Constantly she wondered when and if this strange abduction of her memory would recur. Only when she learned of the compilation of similar statin related cases by a doctor at San Diego medical college did her confidence begin to return and her feelings of anxiety slowly disappear."
Almighty: "Bravo. You have thoroughly entertained me with this colorful anecdote, which my medical advisors tell me could have related just as directly to a purely co-incidental psychomotor seizure or a transient ischemic attack. Do you have any cases that prove anything other than your ability to entertain?"
Candide: "There are many similar cases but I feel I am wasting my mind. As already I have said, "None are so blind as those who will not see."
Almighty: "Perhaps you should be telling all this to Watchover, FDA's mechanism for the reporting of adverse drug reactions. Certainly if we have missed something in our own Shield program, Watchover will pick it up."
Candide: "Watchover was informed of each Baycol death as it occurred during these past two years but bureaucratic inertia allowed over fifty fatalities to occur before action was taken placing the credibility and effectiveness of FDA in serious question. Watchover has been informed of each of these memory loss case reports and after two years of review still has been unable to make a decision. The overwhelming majority of prescribing physicians in the United States today are completely unaware of the potential of statin drugs to alter memory."
Almighty: "Suppose you tell me more of these cases. If nothing else they are quite entertaining."
Candide: "I will continue to entertain you as you wish if for no other reason than the chance, however slight, that the sheer numbers may impress you even though your medical advisors still discount them."
"A husband noted for his sharp mind and ability for almost total recall got out of bed wondering what day of the week it was. His surprised wife quickly ascertained he did not even know what month it was. She reported he nearly drove her crazy asking this same question over and over again despite her repeated reassurance as to time and date. He knew nothing of their stocks and other money matters and could not understand how his wife could know all these things and he could not. Emergency room workup was negative Condition cleared completely after eight hours. Neurologist diagnosed Transient Global Amnesia, cause unknown but Zocor was suspected as it had been started six weeks earlier. The patient discontinued this drug and remained well."
"A university professor who always remembered everything lost an entire day during his first encounter with memory loss while on Lipitor. Weeks later during his second, he was unable remember his social security, telephone or bankcard numbers and could not even remember his birthdate. Suspecting Alzheimer's disease he had himself screened by a neurologist with negative findings. Only after his family doctor fortuitously substituted Pravachol (because of his complaints of co-existing muscle pain) did the amnesia episodes clear completely."
"A young loadmaster in the United States Air Force, who by the way is responsible for the proper loading of our military's huge cargo planes, was given a waiver for flight status for the use of Lipitor for cholesterol control. He soon began to experience multiple episodes of what he termed "short term memory loss". He stopped taking Lipitor immediately after learning of the possibility of such side effects from the Internet and his symptoms slowly regressed. He was very concerned that they persisted for several weeks after stopping the drug."
"A man parked by the side of the road on a dark night was interrogated by a state trooper and found to be lost, not having the slightest recall for traveling to this unusual site far off the beaten track and many miles away from his home. The trooper naturally suspected alcoholism but the man recently had started Lipitor. His attempts to offer this drug as a possible cause for his confusion fell on deaf ears but when several more similar episodes occurred the patient self diagnosed cognitive side effects of Lipitor and stopped the drug. The episodes slowly ceased. Despite his inability to convince his doctor he remains forever certain that his confusion and amnesia were Lipitor related."
"A former CEO of a company, known as a thoroughly competent, high achieving, typically type A personality, had been on Lipitor for nearly three years before being struck down by severe myositis and memory defects. He reported a bizarre episode of total global amnesia three months after discontinuation of the drug. His serum enzymes at that time, though improved, still were moderately elevated. His muscle pain was improving. He remarked to his wife that because their swimming pool, neglected by his recent near incapacitation with muscle pain, was green with algae he had to get some pool chlorine and other supplies. Imagine his surprise when after making a purchase of several gallons of chlorine and returning to his car, he found in the trunk a similar supply of chlorine already purchased. Distraught, he called his wife who determined from the sales slip that he had made the chlorine purchase the day before at a completely different store. He had absolutely no recall for having done this but there was no doubt that he had done it for his daughter had seen him while engaged in this purchase. She had been somewhat concerned because she had waved from her car as they always did and he had not responded. He did not acknowledge her presence in her very distinctive car. Always they had greeted each other with hand waving in a warm friendly fashion. In her judgment there was no possibility that he had not seen her. He simply had not been able to recognize her or the car despite their close proximity. She passed it off as just one of those things until her mother called the next day and they compared notes. The husband and father could function sufficiently to drive to a store and make a credit card purchase yet he was a completely different man who seemed to have regressed in memory then so that he no longer knew his adult daughter. Once having identified this "flashback " sort of a reaction the family began a more serious review of the father's memory problems of the past while still on Lipitor and discovered many more unreported, strange episodes. One time he abruptly realized he inexplicably was on a freeway, heading away form home in the wrong direction from anything he intended to do. He passed it off as being preoccupied. On another occasion he left in the morning to do some shore fishing. Later that day when asked if he went fishing he could not recall and was clearly flustered. On another occasion he called his wife on his cell phone to ask why he was in the Home Depot parking lot. He had planned to run some errands but none involved Home Depot. Woodworking materials were cut repeatedly and remained unused as he cut them out again and again. His wife feels that since the cessation of Lipitor he seems to be improving in that his episodes are less frequent but of course they are better reported in that the entire family is looking for these events and monitoring him closely. His pattern of amnesia episodes illustrate a very important fact about documenting such events - there has to be an observer for accurate reporting. The patient has no recall especially for the more mild events. Only if considerable time has passed or the patient winds up in an usual location, is he prompted to consider that something unusual has occurred. In the absence of an observer any patient history is apt to be very miss-leading."
"I could go on and on with these anecdotes, as you call them, but in my world they are patient case reports and would prompt most doctors to examine them critically, especially doctors affiliated with a pharmaceutical industry. What more can I say? You will note that in most of these cases it is the patient or family members who make the diagnosis not the prescribing doctor, so complete has been your PDR brainwashing."
Almighty: "I admit the shear numbers of reports almost forces a reconsideration of our labeling but remember, we long have stated that memory problems can occur with our statins. We are not our brother's keeper. What more can we do?"
Candide: "If you mean by that statement that your PDR listing of amnesia in its voluminous list of possible side effects absolves you from further responsibility you are wrong. You have not effectively communicated the problem of statin associated cognitive side effects to your doctors. I demand special labeling. I want all prescribing physicians to know of this possibility, however rare, so that when memory problems and growing confusion are reported to them by distraught patients, statin drug side effect should be the first thing the doctor thinks of, not the last. When that time comes I shall be satisfied."
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor