Statins have a significant negative impact on quality-of-life

This study was published in Pharmacotherapy 2009 Jul;29(7):800-11

 

Study title and authors:

Statin-associated adverse cognitive effects: survey results from 171 patients.

Evans MA, Golomb BA.

Department of Medicine, University of California-San Diego, La Jolla, California 92093-0995, USA.

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/19558254

The objective of the study was to characterize the adverse cognitive effects of statins. In the study, a survey was completed by 171 patients (age range 34-86 yrs) who had self-reported memory or other cognitive problems associated with statin therapy.

The study found:
(a) Of 143 patients who reported stopping statin therapy, 128 (90%) reported improvement in cognitive problems, sometimes within days of statin discontinuation.
(b) In some patients, a diagnosis of dementia or Alzheimer's disease reportedly was reversed.
(c) 19 patients whose symptoms improved or resolved after they discontinued statin therapy and who underwent rechallenge with a statin exhibited cognitive problems again (multiple times in some).
(d) Higher potency statins led to higher rates of cognitive-specific adverse drug reaction.
(e) Quality of life was significantly adversely affected.

Evans concludes: "Findings from the survey suggest that cognitive problems associated with statin therapy have variable onset and recovery courses, a clear relation to statin potency, and significant negative impact on quality-of-life".

Statins related to memory dysfunction

This paper was published in Current Drug Safety 2012 Feb;7(1):33-4

Study title and authors:
Statin related memory dysfunction in a Nigerian woman: a case report.

Okeahialam BN, Isiguzoro I.
Department of Medicine, Jos University Teaching Hospital, Jos, Plateau State, Nigeria. basokeam@yahoo.com

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/22663955

This paper describes the case of a woman who with Simvastatin developed memory deficits which adversely affected activities of her daily living.

(i) The woman was first observed in 2005 at 41 years of age for sensation of weight in the chest.
(ii) She was put on atorvastatin (Lipitor) 10 mg daily.
(iii) Levels of her high density lipoprotein (HDL) cholesterol fell and since low HDL cholesterol increases heart disease risk, the drug was withheld.
(iv) In 2008 she restarted statin treatment, this time she took Simvastatin (Simvor) 10 mg daily.
(v) While on this, she complained of feeling ill and cramped up each morning.
(vi) She stopped taking Simvastatin.
(vii) In time Simvastatin was re-introduced at 20mg daily.
(viii) She started to experience muscle cramps, incoherence in thought and speech as well as memory impairment.
(ix) She reduced the dose to 10 mg daily with some respite in the short term.
(x) With time and still on 10mg nocte of simvastatin she once again started to have rising muscle pains. Lapses in memory were also observed. She was not remembering things and to her embarrassment, kept repeating instructions which she had earlier given. The urge to read vanished and if she forced herself to read, she could not absorb.
(xi) She totally discontinued Simvastatin which led to recovery.

Okeahialam also notes that low levels of cholesterol and low levels of low density lipoprotein (LDL) cholesterol may be associated with cognitive dysfunction and concludes: "It is suggested that patients on statins be monitored for side effects especially memory deficits which can adversely effect quality of life... It may also be unwise to reduce the lipid (cholesterol) sub fractions to very low levels".

Statin therapy causes memory complaints and mood changes

This paper was published in Pharmacotherapy 2010;30(6):236e–240e

Study title and authors:

Changes in Memory Function and Neuronal Activation Associated with Atorvastatin Therapy
Beth A. Parker, Ph.D., Donna M. Polk, M.D., Vimal Rabdiya, M.D., Shashwath A. Meda, M.S., Karen Anderson, R.N., Keith A. Hawkins, Psy.D., Godfrey D. Pearlson, M.D., and Paul D. Thompson, M.D.

This paper can be accessed at: http://www.pharmacotherapy.org/Case_Reports/Pharm3006e_Parker-CR.pdf

This paper, headed by Dr Beth Parker from the Hartford Hospital, describes a 65-year-old man who reported cognitive complaints (memory complaints and mood changes) after taking atorvastatin 10 mg/day for one year. He had no history of alcohol consumption, major head trauma, psychiatric problems, or memory impairment.

(i) After one year of taking the statin the patient described his complaints as “fuzzy thinking” and “brain fog.” His wife also noted that the patient demonstrated a progressive decline in cognitive function and memory accompanied by increasing mood changes.

(ii) Cognitive testing and assessment of neuronal activation using functional magnetic resonance imaging (fMRI) (procedure that measures brain activity) were performed during a working memory task while he was receiving atorvastatin therapy.
(iii) The patient demonstrated altered neuronal activation and reduced performance on the cognitive tests, which was consistent with his cognitive symptoms.
(iv) He stopped taking atorvastatin. The cognitive tests were repeated two months after discontinuation of the drug and the patient exhibited improved cognitive test performance and fMRI patterns similar to those expected in a healthy individual.
(v) The patient also reported subjective improvement of his cognitive complaints within days of cessation of atorvastatin.

Dr Parker concludes that a: "growing number of reports suggest that statins evoke adverse cognitive effects".

Statins can impair brain functioning

This paper was published in the Journal of Korean Medical Science 2012 Apr;27(4):458-9

 

Study title and authors:

Reversible dysphasia and statins.

Davies GR.

Department of Psychiatry, University of Wollongong, New South Wales, Australia. alienist@ihug.com.au

 

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/22468114

Dysphasia is a partial or complete impairment of the ability to communicate resulting from brain injury.

This paper, authored by Dr Gordon Davies, presents a case of reversible dysphasia occurring in a patient prescribed atorvastatin.

(i) A 58-year-old woman was presented for medicolegal examination with regard to a compensation claim involving allegations of harassment at work producing anxiety and depression. At the time of her initial presentation for treatment her general practitioner had noted that her blood pressure was higher than usual and had prescribed the statin Lipitor (atorvastatin) 10 mg per day together with indapamide 2.5 mg per day.
(ii) A few days later the patient reported that she had developed problems in "word finding" in that her speech would be interrupted because she would be unable to find a word to describe an object.
(iii) The patient ceased the Lipitor and said that her symptoms had resolved quite quickly.
(iv) The patient then commenced on Crestor (rosuvastatin) 5 mg daily while continuing on indapamide and four weeks later at her medico-legal assessment she was noted to have clear but intermittent difficulty in word finding. She was also tense and tearful at times.
(v) She was reviewed two weeks later. At this point she had stopped the rosuvastatin and her speech was fluent and clear. She was continuing to take indapamide 2.5 mg per day.

This case highlights the possibility that statins can impair brain functioning. Dr Davies concludes: "The immediate inference from the above observations is that the patient had developed dysphasia as a direct side effect of the use of simvastatin. That this is likely to have been a generic statin effect is supported by the recurrence of milder symptoms on rosuvastatin and their remission on its cessation. Using the method of attribution recommended by Naranjo and colleagues, see here, it would rate at 9 (definite adverse reaction)".

Clinicians should be aware of possible adverse cognitive reactions during statin therapy

This paper was published in Pharmacotherapy 2006 Aug;26(8):1190-2

 

Study title and authors:

Short-term memory loss associated with rosuvastatin.

Galatti L, Polimeni G, Salvo F, Romani M, Sessa A, Spina E.

Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, University of Messina, Messina, Italy. lgalatti@unime.it

 

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/16863497

This paper reports the case of rosuvastatin-related short-term memory loss.

(i) A 53-year-old man experienced memory loss after being treated with rosuvastatin at 10 mg per day.
(ii) After discontinuation of rosuvastatin, the neuropsychiatric adverse reaction resolved gradually, suggesting a probable drug association.
(iii) During the following year, the patient remained free from neuropsychiatric disturbances.

The lead researcher of the paper, Dr Laura Galatti, concludes that clinicians should be aware of possible adverse cognitive reactions during statin therapy.

Statins induce a decline in cognition

This paper was published in the Annals of Pharmacotherapy 2006 Oct;40(10):1880-3

Study title and authors:
Simvastatin-induced decline in cognition.

Padala KP, Padala PR, Potter JF.
Geriatrics Section, Department of Internal Medicine, 981320 Nebraska Medical Center, Omaha, NE 68198-1320, USA. kpadala@unmc.edu

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/16940411

This paper describes a case of new-onset cognitive difficulties in an older patient after initiation of simvastatin therapy.

(i) A 64-year-old man developed cognitive difficulties (short-term memory loss, long-term memory loss, and item misplacement) within one week after starting simvastatin 40 mg/day.
(ii) Simvastatin was discontinued, and the patient's cognition improved to normal within six weeks.
(iii) He again tried simvastatin, this time at half the original dose and his cognition deteriorated over a two week period.
(iv) Simvastatin was stopped, and his normal cognition returned within four weeks.

This case shows that statins can induce a decline in cognition.

Statins may adversely affect cognition in patients with dementia

This study was published in the American Journal of Geriatric Pharmacotherapy 2012 Aug 22

Study title and authors:
The Effect of HMG: CoA Reductase Inhibitors on Cognition in Patients With Alzheimer's Dementia: A Prospective Withdrawal and Rechallenge Pilot Study.

Padala KP, Padala PR, McNeilly DP, Geske JA, Sullivan DH, Potter JF.
Geriatric Research Education and Clinical Center, Central Arkansas Veterans Health Administration System, Little Rock, Arkansas; Reynolds Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/22921881

The aim of this study was to evaluate the impact statins have on cognition. The study included 18 older subjects with Alzheimer's dementia who were on statin therapy who underwent a 6-week withdrawal phase of statins followed by a 6-week rechallenge with the drug. The primary outcome measure was cognition, measured by the Mini-Mental State Examination (MMSE).

The mini–mental state examination (MMSE) or Folstein test is a brief 30-point questionnaire test that is used to screen for cognitive impairment. It is commonly used in medicine to screen for dementia. Any score greater than or equal to 25 points (out of 30) indicates a normal cognition. Below this, scores can indicate severe (less than 9 points), moderate (10-20 points) or mild (21-24 points) cognitive impairment.

The study found:
(a) The subjects had an improvement in MMSE scores with discontinuation of statins and a decrease in MMSE scores after rechallenge.
(b) Cholesterol levels increased with statin discontinuation and decreased with rechallenge.

The head investigator of the study, Dr Kalpana P. Padala from the University of Arkansas, concluded that: "The study found an improvement in cognition with discontinuation of statins and worsening with rechallenge. Statins may adversely affect cognition in patients with dementia".

Statins impair brain function

This post includes a synopsis of a study published in the American Journal of Medicine 2000 May;108(7):538-46

Study title and authors:
Effects of lovastatin on cognitive function and psychological well-being.
Muldoon MF, Barger SD, Ryan CM, Flory JD, Lehoczky JP, Matthews KA, Manuck SB.
Center for Clinical Pharmacology (MFM), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/10806282

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The study investigated the relationship between statins and brain function. 209 generally healthy adults with low-density-lipoprotein (LDL) cholesterol level of 160 mg/dL or higher were randomly assigned to 6-month treatment with lovastatin (20 mg) or placebo. Subjects were given neuropsychological tests before the treatment and at six months.

The study found:
(a) After six months placebo-treated subjects improved on neuropsychological tests in all five performance domains, consistent with the effects of practice on test performance, whereas those treated with lovastatin improved only on tests of memory recall.
(b) Subjects on statins showed a significant worsening of attention and slowing down of thought compared to subjects on placebo.

To conclude: Statins impair brain function.

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Statins may be detrimental to cognitive functioning

This post includes a summary of a paper published in The American Journal of Medicine Volume 117, Issue 11, Pages 823-829 1 December 2004

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Study title and authors:

Randomized trial of the effects of simvastatin on cognitive functioning in hypercholesterolemic adults

Matthew F. Muldoon, MD, MPHa, Christopher M. Ryan, PhDb, Susan M. Sereika, PhDc, Janine D. Flory, PhDd, Stephen B. Manuck, PhDd

This study can be accessed at: http://www.amjmed.com/article/S0002-9343(04)00546-7/abstract

The study investigated the effects of statin therapy on cognitive functioning. The study, which employed a randomized double-blind design, comprised 308 adults between 35 and 70 years of age who had low density lipoprotein (LDL) cholesterol levels between 160 - 220 mg/dL (4.1 - 5.7 mmol/L). For six months the participants were assigned to daily treatment of either:
(i) Placebo.
(ii) 10 mg of simvastatin.
(iii) 40 mg of simvastatin.

Neuropsychological tests were administered to assess cognitive functioning at the start of the study and at the end of the treatment period.

Based on observations from a previous study, the tests were grouped into three categories:
(1) Statin sensitive tests:

Elithorn Mazes: Planning and drawing time to complete complex lattice-type perceptual mazes.

Digit Vigilance: Number of target stimuli (the number “6”) missed when required to scan two pages

of numbers.

Recurring Words: Percentage of words identified correctly as either “new” or “repeated” when words are read using a continuous recognition test format.

Grooved Pegboard: Time required to insert 25 grooved pegs into slotted holes.

 

(2) Statin insensitive tests:

Digit Symbol: Time required to recode numbers into symbols using a key that pairs each of nine digits with a meaningless shape. Time converted to scaled, normalized score.

Stroop Interference: Viewing a list of color words printed in an incongruous ink color, participants say each ink color as quickly as possible (seeing “red” printed in blue ink, they respond “blue”). Number correct is converted to a scaled, normalized score.

Trail Making B: Time required to draw a line connecting alternating numbers and letters (e.g., 1-A-2-B) that are arrayed on a piece of paper.

Digit Span: Longest span of digits correctly recalled forwards and longest span recalled backwards. Sum of spans is converted into scaled, normalized score.

Complex Figure: Score on the reproduction of the Rey or Taylor figure, drawn from memory 30 minutes after having copied the figure.

Letter Rotation: Number of stimuli (the letters F, L, or R rotated 0°, 30°, 60°, 90°, 120°, 150°, or 180°) misidentified as being either oriented normally or reversed.

 

(3) New tests:

Mirror Tracing: Number of errors made when tracing over a star pattern that can be seen only in mirror-reversed view.

4-Word Short-Term Memory: Across several trials, the number of words correctly recalled after intervening distraction consisting of serial subtraction arithmetic for 15 or 30 seconds.

The study found:
(a) In the statin sensitive tests, patients on placebo improved their perfomance, whilst patients on statins did not.
(b) In the statin insensitive tests there was little difference between the placebo and statin groups, although the placebo group improved slightly more than the statin groups.
(c) In the new tests, cognition improved more in the placebo group compared to the statin groups.

The results of the study reveal that statins may be detrimental to cognitive functioning.

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Doctor's low awareness of statin side effects

This post includes a summary of a study published in the American Journal of Cardiovascular Drugs: 1 November 2008 - Volume 8 - Issue 6 - pp 373-418

Study title and authors:
Statin Adverse Effects: A Review of the Literature and Evidence for a Mitochondrial Mechanism
Golomb, Beatrice A; Evans, Marcella A

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Dr Beatrice Golomb reviewed the scientific literature regarding the adverse effects caused by statin drugs.

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/19159124

Dr Golomb found:
(a) Muscle adverse events were the most reported problem both in the literature and by patients.
(b) In meta-analyses of randomized controlled trials, muscle adverse events are more frequent with statins than with placebo.
(c) A number of manifestations of muscle adverse eventss have been reported, with rhabdomyolysis the most feared.
(d) Adverse events are dose dependent, and risk is amplified by drug interactions that functionally increase statin potency.
(e) An array of additional risk factors for statin AEs are those that amplify (or reflect) mitochondrial or metabolic vulnerability, such as metabolic syndrome factors, thyroid disease, and genetic mutations linked to mitochondrial dysfunction.
(f) Converging evidence supports a mitochondrial foundation for muscle adverse events associated with statins, and both theoretical and empirical considerations suggest that mitochondrial dysfunction may also underlie many nonmuscle statin adverse events.
(g) Evidence from randomized controlled trials and studies of other designs indicates existence of additional statin-associated adverse events, such as cognitive loss, neuropathy, pancreatic and hepatic dysfunction, and sexual dysfunction.
(h) Physician awareness of statin advers events is reportedly low even for the adverse events most widely reported by patients.
(i) Awareness and vigilance for adverse events should be maintained to enable informed treatment decisions, treatment modification if appropriate, improved quality of patient care, and reduced patient morbidity.

The paper outlines the unhealthy adverse effects of statins and that doctors have a low awareness of the problems.

 
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Statins And Cancer: Cause For Concern

This post featues a paper published in the British Medical Journal 17 November 2001;323:1145

Study title and authors:
Statins And Cancer: Cause For Concern
Uffe Ravnskov, Paul J. Rosch, Peter H.Langsjoen, Joel M. Kauffman, and Kilmer S. McCully
Magle Stora Kyrkogata 9, S-22350 Lund, Sweden.
This paper can be accessed at: http://www.bmj.com/cgi/eletters/323/7322/1145#26439
 
Dr Uffe Ravnskov has published over 80 scientific papers regarding the cholesterol, saturated fat, heart disease hypothesis. Here he questions the wisdom of recommending statin treatment for a large segment of the world’s population simply because they have elevated cholesterol levels or are assumed to be at increased risk for coronary events because of the presence of other risk markers.

He finds:
(i) It is already known that statins may induce fatal rhabdomyolysis, cardiac insufficiency, peripheral polyneuropathy, hepatic toxicity, and mental disturbances.
(ii) A much more momentous issue is that all statins have proven carcinogenic.
(iii) In the Heart Protection Study non-melanoma skin cancer was seen in 243 patients treated with simvastatin compared with 202 cases in the control group. 
(iv) In the Scandinavian Simvastatin Survival Study non-melanoma skin cancer was seen in 13 patients treated with simvastatin compared with six in the control group.
(v) Also disquieting was the significant increase in breast cancer rates in patients treated with pravastatin in the Cholesterol and Recurrent Events trial.

Dr says clinicians should be aware of cognitive impairment and dementia as potential adverse effects associated with statin therapy

This post contains a summary of a paper published in Pharmacotherapy 2003 Dec;23(12):1663-7

Study title and authors:

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Cognitive impairment associated with atorvastatin and simvastatin.

King DS, Wilburn AJ, Wofford MR, Harrell TK, Lindley BJ, Jones DW.

Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA. dking@pharmacy.umsmed.edu

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/14695047
 
This paper reports of two women who experienced significant cognitive impairment related to statin therapy. One woman took atorvastatin, and the other first took atorvastatin, then was rechallenged with simvastatin.

Both of the patients showed decreased cognition that was slow in onset, with progressively worsening symptoms related to statin therapy. In both patients, the cognitive impairment completely resolved within one month after statin discontinuation.

Patient 1
(i) A 67-year-old woman was been treated for high blood pressure, "high" cholesterol and type two diabetes.
(ii) The patient was taking levothyroxine, hormone replacement therapy, glyburide, lisinopril, metoprolol, and atorvastatin. Two months before the patient's visit, her atorvastatin dosage had been increased from 10 mg to 20 mg/day. The patient had been taking 10 mg/day for one year with no reported adverse effects. No other changes to the patient's drug regimen had been made.
(iii) The patient experienced new-onset cognitive impairment, which was reported by the patient and her family. Significant impairment in short-term memory was demonstrated on mental status examination. Her family reported behavior changes characterized by mood alteration, lack of interest in routine activities, diminished memory, and social impairment.
(iv) Atorvastatin was discontinued, and one month later, the patient and her family noted a dramatic improvement in her mood, memory, motivation, and a return to normal functioning. Repeated mental status examination also demonstrated remarkable improvement in her short-term memory.

Patient 2
(i) A 68-year-old woman came to a hypertension referral center for initial evaluation. She reported a 20-year personal medical history of high blood pressure. The patient had no known drug allergies, no history of smoking or alcohol consumption, and no psychiatric history or memory impairment. She reported an active lifestyle, with a healthy diet and routine, structured exercise at least five days per week; her long-term drug regimen consisted of lisinopril, estradiol, and atenolol.
(ii) The patient's assessment revealed intact memory with normal judgment and insight. Although her blood pressure was not optimally controlled, physical examination was unremarkable. Hydrochlorothiazide was added to her drug regimen at her initial visit. After laboratory assessment revealed "high" cholesterol, atorvastatin 10 mg per day was begun.
(iii) Approximately nine months after the initial visit, the patient's daughter reported noticeable memory impairment, cognitive decline, and behavior changes. According to the daughter, the patient was forgetting scheduled routine social events and appointments. She also neglected her longstanding exercise program and had complaints of weakness in her extremities and a lack of energy. The daughter felt that the progressive cognitive decline and symptoms were associated with the start of atorvastatin therapy.
(iv) The patient discontinued atorvastatin on her own, which resulted in both physical and cognitive improvement in one week, as reported by the patient and her daughter.
(v) The patient was rechallenged with atorvastatin one month after her symptoms resolved, and the cognitive impairment and other symptoms returned three weeks later.
(vi) Atorvastatin was again discontinued; no other changes were made in concurrent drugs. After one month the patient reported memory improvement and resolution of weakness and tiredness. Mental status examination demonstrated a return to baseline. She had also resumed her routine exercise and social activities.
(vii) She then started Simvastatin 20 mg per day.
(viii) Approximately seven weeks later, the patient and her daughter called to report a return of the memory impairment and cognitive decline. The patient also had complaints of lower extremity weakness and aches.
(ix) Simvastatin was discontinued and, once again, her symptoms resolved in three weeks.

Cholesterol is essential in the formation of myelin. (Myelin is a substance rich in fats and proteins that forms layers around the nerve fibers and acts as insulation. The nerve can be likened to an electrical cable; the axon, or nerve fiber that transmits the nerve impulse, is like the copper wire; and the myelin sheath is like the insulation around the wire. Myelin is present in both the central nervous system and the peripheral nervous system).

Statin-induced dementia may be caused by statins decreasing the amount of central nervous system cholesterol below the critical value necessary for the formation of myelin. Inadequate myelin production results in demyelination of nerve fibers in the central nervous system, resulting in memory loss.

Once the offending statin is removed from the patient's system, myelin stores are replenished and mental status returns to normal. In the two patients, who received simvastatin, mental status returned to normal within one month of discontinuing the statin.

In addition to demyelination of nerves in the central nervous system, nerves in the peripheral nervous system may be affected. Patients may experience tingling sensations of the extremities and loss of the sense of touch secondary to peripheral nervous system demyelination. The second patient experienced some peripheral adverse effects.

Dr. King concludes: "Clinicians should be aware of cognitive impairment and dementia as potential adverse effects associated with statin therapy".

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Statin adverse effects

This post features an article by Beatrice A. Golomb, M.D.

Statin Adverse Effects: Implications for the Elderly
by Beatrice A. Golomb, M.D., Ph.D.

Geriatric Times May/June 2004 Vol. V Issue 3

Statins, or 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (e.g., atorvastatin [Lipitor], simvastatin [Zocor]), are among the best-selling prescription drugs in the world and are widely viewed as very safe and effective. Their benefits to coronary artery disease have been copiously documented and are incontrovertible. In addition, statins have been shown to benefit survival in a large study of middle-aged men with, or at high risk for, heart disease (Scandinavian Simvastatin Survival Study Group, 1994). Nonetheless, all drugs have potential adverse reactions despite their potential benefits. Understanding these risks is vitally important, particularly in elderly patients in whom both risks and benefits differ relative to younger patients.

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Evidence suggests the balance of benefits to risks may be less favorable in the elderly: Cholesterol becomes a less potent predictor of cardiovascular problems, and adverse reactions from drugs, including statins, may become more prominent. While patients at high risk for cardiovascular disease receive mortality benefit from statins in studies predominating in middle-aged men (Scandinavian Simvastatin Survival Study Group, 1994), no trend toward survival benefit is seen in elderly patients at high risk for cardiovascular disease (Shepherd et al., 2002). A less favorable risk-benefit profile may particularly hold for patients older than 85, in whom benefits may be more attenuated and risks more amplified (Weverling-Rijnsburger et al., 1997). In fact, in this older group, higher cholesterol has been linked observationally to improved survival. This paper will review a selection of the risks and adverse effects of statins that have special implications for elderly patients.

Muscle Problems

Muscle problems are the most common reported adverse effects of statins, according to an observational database maintained by the University of California at San Diego Statin Study group. Perhaps the most feared adverse effect of statins is rhabdomyolysis--a condition in which there is severe breakdown of muscle tissue that may be toxic to the kidneys and result in kidney failure or death. The muscle breakdown commonly leads to a strong elevation in blood levels of muscle enzyme creatine kinase (CK). Creatine kinase levels often exceed 10 times the upper limit of normal in cases of frank rhabdomyolysis. Fatal rhabdomyolysis occurred with increased frequency with cerivastatin (Baycol) when used at higher doses or in combination with gemfibrozil (Lopid); cerivastatin was removed from the U.S. market in 2001. Rhabdomyolysis occurs with all statins, although the actual frequency of occurrence is quite low.

Physicians are most familiar with rhabdomyolysis, and many suppose that for muscle pain to be statin-associated, it must induce muscle symptoms throughout the body coupled with elevation of CK levels. However, this reflects only one manifestation of statin-associated muscle symptoms. Some patients have only new focal pain or new fatigue, and may have mild or no elevation in CK levels. In some instances these symptoms progress to rhabdomyolysis--one reason to take these symptoms seriously--but many times they do not.

An important double-blind, crossover biopsy study showed that some patients receiving statin therapy with non-CK-elevating muscle pain have objectively documentable, partially reversible mitochondrial myopathy (Phillips et al., 2002). Even in the absence of rhabdomyolysis or CK elevation, major effects on function and quality of life may occur (Golomb et al., 2003). It is important to note that in both our experience and that of others, muscle symptoms precipitated by statins may not in all cases completely recover; this is consistent with the finding that, pathologically, the myopathy may not completely reverse.

Adverse muscle problems from statins, in addition to rhabdomyolysis, take a variety of forms (Table). Shortness of breath sometimes accompanies statin-associated muscle problems. The "respiratory exchange ratio"--the ratio of carbon dioxide exhaled per oxygen inhaled--is altered in people with statin myotoxicity (Phillips et al., 2004). Occasionally, shortness of breath is the predominant symptom. Patients may experience marked shortness of breath that occurs following initiation of statin therapy and is sustained while statins are continued for which no etiology is identified on extensive cardiopulmonary workup. These symptoms resolve completely with statin discontinuation.

Muscle problems associated with statins may be more common among the elderly. In the 2002 American College of Cardiology/American Heart Association/National Heart, Lung, and Blood Institute Clinical Advisory on the Use and Safety of Statins, Pasternak et al. noted the following factors that may increase the risk for statin-associated myopathy:

 advanced age (especially >80 years, women > men);

 small body frame and frailty;

 multisystem disease;

 multiple medications;

 perioperative periods; and

 concurrent use of certain medications.

These factors are especially common among the elderly, which places them at increased risk for development of muscle problems with statins.

Muscle problems associated with statins may be more debilitating among the elderly. When muscle problems occur, they may have more impact on the elderly. Elderly patients more commonly have already declined in muscle strength and function; and are often already on, or perched near, the steep part of the curve relating muscle strength to physical function, independence and the ability to perform activities of daily living. Thus, the same amount or proportion of compromise in muscle function may have a substantially more profound impact on quality of life in elderly patients. In addition, reductions in physical function, indexed by reductions in lower extremity function, are linked to self-reported disability, hospitalizations, admissions to nursing homes and mortality from all causes (Guralnik et al., 2000, 1995, 1994; Penninx et al., 2000). Reductions in lower extremity function are associated with reduced physical activity (McDermott et al., 2002), so that such patients may lose the protection that exercise is reported to afford against a host of conditions.

Cognitive Loss

Cognitive problems also occur with statins and may also have more impact in elderly patients. Two randomized trials that were designed to assess cognitive effects of statins have shown worsening in cognitive function (Muldoon et al., 2002, 2000). In addition, several case reports (King et al., 2003, 2001; Orsi et al., 2001) and one large case series (involving 60 patients) (Wagstaff et al., 2003) have reported deleterious cognitive effects of statins on memory and cognitive function.

Although not expressly designed to assess cognition, results from the Heart Protection Study (HPS) (Heart Protection Study Collaborative Group, 2002) and PROSPER trial (Shepherd et al., 2002) did not show that statin therapy had favorable or deleterious effects on cognitive measures that were tested. Several factors may help to explain the discrepancy between findings from these large and smaller trials targeted at testing cognition. First, different measures of cognition were used that may not have tapped the areas in which problems occur. The telephone survey measure in the HPS, for instance, would not have captured visuomotor coordination and processing speed, which the other trials suggested may be particularly affected.

Second, the large trials enrolled people at high risk for cardiovascular disease who experience benefit from statins to nonfatal stroke, which may lead to improvements in cognition that may help to balance out harms to cognition from other mechanisms. Although there are trends toward increases in fatal stroke with statins in most of the large statin trials, those who have died cannot complete cognitive surveys. The impact on total number of strokes was unaffected in the PROSPER trial with its sole focus on the elderly population. In the PROSPER trial, the number of reduced transient ischemic attacks and nonfatal strokes was actually matched by a similar number of increased fatal strokes.

Finally, the HPS used what is termed an "active run-in." For six weeks, participants considered for enrollment were placed on simvastatin, and those who were not fully compliant were dropped from the study. Participants who perceived problems on the drug, including cognitive problems, may have dropped the study themselves or skipped pills intentionally. In addition, participants who developed memory problems may have had trouble remembering to take the pills even if they did not recognize deterioration in cognitive function. This run-in process may have excluded participants who developed cognitive problems on the drug, selecting only those who did not experience problems. Over one-third of those who were interested in enrolling were excluded following this compliance run-in.

Because statins reduce nonfatal stroke (and cognition is obviously not measured in people who have experienced fatal stroke), benefits by statins for cognitive function in those in whom a stroke was averted might be expected. It must be emphasized that the randomized trial evidence has, to date, uniformly failed to show cognitive benefits by statins and has supported no effect or frank and significant harm to cognitive function.

Analogous to the case for muscle adverse effects, the impact of cognitive adverse effects from statins, when they occur, may be more profound in the elderly. Elderly patients have more commonly already experienced some decline in cognitive function, and more commonly are in a vulnerable range in which additional impairment can have an impact on independence and safety. Indeed, a number of studies show that even modest reductions in cognition in the elderly are linked to increased mortality, even when the reductions remain within the nondemented range, and even when other health factors have been controlled for (Bassuk et al., 2000; Frisoni et al., 1999; Korten et al., 1999; Smits et al., 1999). In this context, adverse cognitive effects must be taken seriously not only for their intrinsic impact on quality of life, but for their potentially weighty implications for mortality.

Other Adverse Effects

A large variety of other adverse effects have been reported with statins, including (but not limited to) gastrointestinal and neurological effects, psychiatric problems, immune effects (e.g., lupus-like syndrome), erectile dysfunction and gynecomastia (breast enlargement in men), rash and skin problems, and sleep problems.

Of particular note for the elderly population, the PROSPER trial found a significant 25% increase in incident cancer in participants over age 70 randomized to statin therapy versus placebo (Shepherd et al., 2002). Because statins have been reported to cause cancer in animals, the significant increase in cancer cannot be dismissed as necessarily a fluke. While a similar increase has not been seen in studies of statins in younger participants, older people have poorer stores of the cancer-protecting antioxidant nutrients that low-density lipoprotein cholesterol helps to transport to tissue (so that the increase in risk may occur selectively in elderly). Even if the fractional change in risk were similar, the elderly have a higher risk of cancer, increasing the number of cancer events that would manifest.

Low cholesterol is also linked to infection, including development of postoperative infection (Leardi et al., 2000) and predicts mortality and adverse outcomes in hospitalized patients (Crook et al., 1999). While some of this could be due to illness causing lower cholesterol, it may also be that low cholesterol contributes to illness; indeed, animal studies suggest lipoproteins may serve to protect against bacterial endotoxin-induced death (Read et al., 1993).

Statins may produce irritability or short temper in some people, a problem that occurs with statin therapy and resolves with its discontinuation (Golomb et al., 2004). For elderly patients who depend on others for assistance, irritability and its impact on the relationship with caregivers may have special implications.

Heart failure may also occur in patients taking statin therapy. In some people, the myopathic effects of statins may impair heart pumping function (Silver et al., 2003). However, in patients with reduced pumping function due to coronary artery blockages, statins may help heart pumping by improving blood flow to the heart (Node et al., 2003). It depends on the person whether benefit or harm dominates with statin therapy.

Discussion

Observational studies show that as age increases within the elderly age range, high cholesterol flattens then reverses as a risk factor for mortality (Weverling-Rijnsburger et al., 1997). Although it remains to be fully clarified whether these findings have relevance to cholesterol-lowering treatment, the exclusive major randomized trial of statins conducted in the elderly does nothing to dispel a possible causal association, as it did not show benefit of statins to survival. The impact was completely neutral on mortality despite selecting for an elderly population at only moderately older age and selecting for particularly high risk of heart disease--the elderly group in whom greater benefits and lower risks would be expected (Shepherd et al., 2002). There are reasons for concern that still older people--those elderly not selecting for high cardiac risk and those who are frailer than clinical trials generally select--might fare less well. Caution should be exercised in provision of statins as with all treatments in elderly patients. Any time a patient develops a new problem or worsening of an existing problem, the medication list should be reviewed and a possible contribution by medications should be considered. This principle is by no means confined to statins. It is particularly true in elderly patients who may be on many medications with interacting effects, and in whom ability to withstand adverse drug reactions may be attenuated.

Acknowledgement

Dr. Golomb would like to thank Tram Dang for research assistance and Janis Ritchie, R.N., for administrative assistance.

Dr. Golomb is on the faculty of the department of medicine and family and preventive medicine at the University of California, San Diego. Her research focuses on the risks and benefits of medical interventions.

References

Bassuk SS, Wypij D, Berkman LF (2000), Cognitive impairment and mortality in the community-dwelling elderly. Am J Epidemiol 151(7):676-688.

Crook MA, Velauthar U, Moran L, Griffiths W (1999), Hypocholesterolaemia in a hospital population. Ann Clin Biochem 36(pt 5):613-616.

Frisoni GB, Fratiglioni L, Fastbom J et al. (1999), Mortality in nondemented subjects with cognitive impairment: the influence of health-related factors. Am J Epidemiol 150(10):1031-1044.

Golomb BA, Kane T, Dimsdale JA (2004), Severe irritability associated with statin cholesterol-lowering drugs. QJM 97(4):229-235.

Golomb BA, Yang E, Denenberg J, Criqui M (2003), Statin-associated adverse events. P95. Presented at the 43rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention. Miami; March 5-8.

Guralnik JM, Ferrucci L, Pieper CF et al. (2000), Lower extremity function and subsequent disability: consistency across studies, predictive models, and value of gait speed alone compared with the short physical performance battery. J Gerontol A Biol Sci Med Sci 55(4):M221-M231.

Guralnik JM, Ferrucci L, Simonsick EM et al. (1995), Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability. N Engl J Med 332(9):556-561 [see comment].

Guralnik JM, Simonsick EM, Ferrucci L et al. (1994), A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol 49(2):M85-M94.

Heart Protection Study Collaborative Group (2002), MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360(9326):7-22 [see comments].

King DS, Jones DW, Wofford MR et al. (2001), Cognitive impairment associated with atorvastatin. Presented at the American College of Clinical Pharmacy Spring Practice and Research Forum. Salt Lake City; April 22-25.

King DS, Wilburn AJ, Wofford MR et al. (2003), Cognitive impairment associated with atorvastatin and simvastatin. Pharmacotherapy 23(12):1663-1667.

Korten AE, Jorm AF, Jiao Z et al. (1999), Health, cognitive, and psychosocial factors as predictors of mortality in an elderly community sample. J Epidemiol Community Health 53(2):83-88.

Leardi S, Altilia F, Delmonaco S et al. (2000), [Blood levels of cholesterol and postoperative septic complications.] Ann Ital Chir 71(2):233-237.

McDermott MM, Greenland P, Ferrucci L et al. (2002), Lower extremity performance is associated with daily life physical activity in individuals with and without peripheral arterial disease. J Am Geriatr Soc 50(2):247-255.

Muldoon MF, Barger SD, Ryan CM et al. (2000), Effects of lovastatin on cognitive function and psychological well-being. Am J Med 108(7):538-546.

Muldoon MF, Ryan CM, Flory JD, Manuck SB (2002), Effects of simvastatin on cognitive functioning. Presented at the American Heart Association Scientific Sessions. Chicago; Nov. 17-20.

Node K, Fujita M, Kitakaze M et al. (2003), Short-term statin therapy improves cardiac function and symptoms in patients with idiopathic dilated cardiomyopathy. [Published erratum Circulation 108(17):2170.] Circulation 108(7):839-843.

Orsi A, Sherman O, Woldeselassie Z (2001), Simvastatin-associated memory loss. Pharmacotherapy 21(6):767-769.

Pasternak RC, Smith SC, Bairey-Merz CN et al. (2002), ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of Statins. Stroke 33(9):2337-2341 [see comment].

Penninx BW, Ferrucci L, Leveille SG et al. (2000), Lower extremity performance in nondisabled older persons as a predictor of subsequent hospitalization. J Gerontol A Biol Sci Med Sci 55(11):M691-M697.

Phillips PS, Haas RH, Bannykh S et al. (2002), Statin-associated myopathy with normal creatine kinase levels. Ann Intern Med 137(7):581-585 [see comments].

Phillips CT, Gray NL, Puhek LM et al. (2004), Basal respiratory exchange ratio is altered with statin use in normals. J Am Cardio 43(suppl A):233a.

Read TE, Harris HW, Grunfeld C et al. (1993), The protective effect of serum lipoproteins against bacterial lipopolysaccharide. Eur Heart J 14(suppl K):125-129.

Scandinavian Simvastatin Survival Study Group (1994), Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344(8934):1383-1389.

Shepherd J, Blauw GJ, Murphy MB et al. (2002), Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 360(9346):1623-1630 [see comments].

Silver MA, Langsjoen PH, Szabo S et al. (2003), Statin cardiomyopathy? A potential role for coenzyme Q10 therapy for statin-induced changes in diastolic LV performance: description of a clinical protocol. Biofactors 18(1-4):125-127.

Smits CH, Deeg DJ, Kriegsman DM, Schmand B (1999), Cognitive functioning and health as determinants of mortality in an older population. Am J Epidemiol 150(9):978-986.

Wagstaff LR, Mitton MW, Arvik BM, Doraiswamy PM (2003), Statin-associated memory loss: analysis of 60 case reports and review of the literature. Pharmacotherapy 23(7):871-880.

Weverling-Rijnsburger AW, Blauw GJ, Lagaay AM et al. (1997), Total cholesterol and risk of mortality in the oldest old. [Published erratum Lancet 351(9095):70.] Lancet 350(9085):1119-1123 [see comment].

This article can be accessed at: http://www.cmellc.com/geriatrictimes/g040618.html

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Statin dangers

This post features an article about the dangers of statin drugs

Dangers of Statin Drugs: What You Haven’t Been Told About Popular Cholesterol-Lowering Medicines
By Sally Fallon and Mary G. Enig, PhD

Hypercholesterolemia is the health issue of the 21st century. It is actually an invented disease, a "problem" that emerged when health professionals learned how to measure cholesterol levels in the blood. High cholesterol exhibits no outward signs--unlike other conditions of the blood, such as diabetes or anemia, diseases that manifest telltale symptoms like thirst or weakness--hypercholesterolemia requires the services of a physician to detect its presence. Many people who feel perfectly healthy suffer from high cholesterol--in fact, feeling good is actually a symptom of high cholesterol!

Books:

Doctors who treat this new disease must first convince their patients that they are sick and need to take one or more expensive drugs for the rest of their lives, drugs that require regular checkups and blood tests. But such doctors do not work in a vacuum--their efforts to convert healthy people into patients are bolstered by the full weight of the US government, the media and the medical establishment, agencies that have worked in concert to disseminate the cholesterol dogma and convince the population that high cholesterol is the forerunner of heart disease and possibly other diseases as well.

Who suffers from hypercholesterolemia? Peruse the medical literature of 25 or 30 years ago and you’ll get the following answer: any middle-aged man whose cholesterol is over 240 with other risk factors, such as smoking or overweight. After the Cholesterol Consensus Conference in 1984, the parameters changed; anyone (male or female) with cholesterol over 200 could receive the dreaded diagnosis and a prescription for pills. Recently that number has been moved down to 180. If you have had a heart attack, you get to take cholesterol-lowering medicines even if your cholesterol is already very low--after all, you have committed the sin of having a heart attack so your cholesterol must therefore be too high. The penance is a lifetime of cholesterol-lowering medications along with a boring lowfat diet. But why wait until you have a heart attack? Since we all labor under the stigma of original sin, we are all candidates for treatment. Current edicts stipulate cholesterol testing and treatment for young adults and even children.

The drugs that doctors use to treat the new disease are called statins--sold under a variety of names including Lipitor (atorvastatin), Zocor (simvastatin), Mevacor (lovastatin) and Pravachol (pravastatin).

How Statins Work

The cholesterol production process begins with acetyl-CoA, a two-carbon molecule sometimes referred to as the "building block of life." Three acetyl-CoA molecules combine to form six-carbon hydroxymethyl glutaric acid (HMG). The step from HMG to mevalonate requires an enzyme, HMG-CoA reductase. Statin drugs work by inhibiting this enzyme--hence the formal name of HMG-CoA reductase inhibitors. Herein lies the potential for numerous side effects, because statin drugs inhibit not just the production of cholesterol, but a whole family of intermediary substances, many if not all of which have important biochemical functions in their own right.

Consider the findings of pediatricians at the University of California, San Diego who published a description of a child with an hereditary defect of mevalonic kinase, the enzyme that facilitates the next step beyond HMG-CoA reductase.1 The child was mentally retarded, microcephalic (very small head), small for his age, profoundly anemic, acidotic and febrile. He also had cataracts. Predictably, his cholesterol was consistently low--70-79 mg/dl. He died at the age of 24 months. The child represents an extreme example of cholesterol inhibition, but his case illuminates the possible consequences of taking statins in strong doses or for a lengthy period of time--depression of mental acuity, anemia, acidosis, frequent fevers and cataracts.

Cholesterol is one of three end products in the mevalonate chain. The two others are ubiquinone and dilochol. Ubiquinone or Co-Enzyme Q10 is a critical cellular nutrient biosynthesized in the mitochondria. It plays a role in ATP production in the cells and functions as an electron carrier to cytochrome oxidase, our main respiratory enzyme. The heart requires high levels of Co-Q10. A form of Co-Q10 called ubiquinone is found in all cell membranes where it plays a role in maintaining membrane integrity so critical to nerve conduction and muscle integrity. Co-Q10 is also vital to the formation of elastin and collagen. Side effects of Co-Q10 deficiency include muscle wasting leading to weakness and severe back pain, heart failure (the heart is a muscle!), neuropathy and inflammation of the tendons and ligaments, often leading to rupture.

Dolichols also play a role of immense importance. In the cells they direct various proteins manufactured in response to DNA directives to their proper targets, ensuring that the cells respond correctly to genetically programmed instruction. Thus statin drugs can lead to unpredictable chaos on the cellular level, much like a computer virus that wipes out certain pathways or files.

Squalene, the immediate precursor to cholesterol, has anti-cancer effects, according to research.

The fact that some studies have shown that statins can prevent heart disease, at least in the short term, is most likely explained not by the inhibition of cholesterol production but because they block the creation of mevalonate. Reduced amounts of mevalonate seem to make smooth muscle cells less active, and platelets less able to produce thromboxane. Atherosclerosis begins with the growth of smooth muscle cells in side artery walls and thromboxane is necessary for blood clotting.

Cholesterol

Of course, statins inhibit the production of cholesterol--they do this very well. Nowhere is the failing of our medical system more evident than in the wholesale acceptance of cholesterol reduction as a way to prevent disease--have all these doctors forgotten what they learned in biochemistry 101 about the many roles of cholesterol in the human biochemistry? Every cell membrane in our body contains cholesterol because cholesterol is what makes our cells waterproof--without cholesterol we could not have a different biochemistry on the inside and the outside of the cell. When cholesterol levels are not adequate, the cell membrane becomes leaky or porous, a situation the body interprets as an emergency, releasing a flood of corticoid hormones that work by sequestering cholesterol from one part of the body and transporting it to areas where it is lacking. Cholesterol is the body’s repair substance: scar tissue contains high levels of cholesterol, including scar tissue in the arteries.

Cholesterol is the precursor to vitamin D, necessary for numerous biochemical processes including mineral metabolism. The bile salts, required for the digestion of fat, are made of cholesterol. Those who suffer from low cholesterol often have trouble digesting fats. Cholesterol also functions as a powerful antioxidant, thus protecting us against cancer and aging.

Cholesterol is vital to proper neurological function. It plays a key role in the formation of memory and the uptake of hormones in the brain, including serotonin, the body’s feel-good chemical. When cholesterol levels drop too low, the serotonin receptors cannot work. Cholesterol is the main organic molecule in the brain, constituting over half the dry weight of the cerebral cortex.

Finally, cholesterol is the precursor to all the hormones produced in the adrenal cortex including glucocorticoids, which regulate blood sugar levels, and mineralocorticoids, which regulate mineral balance. Corticoids are the cholesterol-based adrenal hormones that the body uses in response to stress of various types; it promotes healing and balances the tendency to inflammation. The adrenal cortex also produces sex hormones, including testosterone, estrogen and progesterone, out of cholesterol. Thus, low cholesterol--whether due to an innate error of metabolism or induced by cholesterol-lowering diets and drugs--can be expected to disrupt the production of adrenal hormones and lead to blood sugar problems, edema, mineral deficiencies, chronic inflammation, difficulty in healing, allergies, asthma, reduced libido, infertility and various reproductive problems.

Enter the Statins

Statin drugs entered the market with great promise. They replaced a class of pharmaceuticals that lowered cholesterol by preventing its absorption from the gut. These drugs often had immediate and unpleasant side effects, including nausea, indigestion and constipation, and in the typical patient they lowered cholesterol levels only slightly. Patient compliance was low: the benefit did not seem worth the side effects and the potential for use very limited. By contrast, statin drugs had no immediate side effects: they did not cause nausea or indigestion and they were consistently effective, often lowering cholesterol levels by 50 points or more. During the last 20 years, the industry has mounted an incredible promotional campaign--enlisting scientists, advertising agencies, the media and the medical profession in a blitz that turned the statins into one of the bestselling pharmaceuticals of all time. Sixteen million Americans now take Lipitor, the most popular statin, and drug company officials claim that 36 million Americans are candidates for statin drug therapy. What bedevils the industry is growing reports of side effects that manifest many months after the commencement of therapy; the November 2003 issue of Smart Money magazine reports on a 1999 study at St. Thomas’ Hospital in London (apparently unpublished), which found that 36 percent of patients on Lipitor’s highest dose reported side effects; even at the lowest dose, 10 percent reported side effects.2

Muscle Pain and Weakness

The most common side effect is muscle pain and weakness, a condition called rhabdomyolysis, most likely due to the depletion of Co-Q10, a nutrient that supports muscle function. Dr. Beatrice Golomb of San Diego, California is currently conducting a series of studies on statin side effects. The industry insists that only 2-3 percent of patients get muscle aches and cramps but in one study, Golomb found that 98 percent of patients taking Lipitor and one-third of the patients taking Mevachor (a lower-dose statin) suffered from muscle problems.3 A message board devoted to Lipitor at forum.ditonline.com (update 09 JUL 2007: reader alerted us the forum is now defunct) contained more than 800 posts, many detailing severe side effects. The Lipitor board at www.rxlist.com contains more than 2,600 posts (click on Message Boards at upper left and then choose Lipitor; also note that as of 09 JUL 2007 there are 3,857 messages).

The test for muscle wasting or rhabdomyolysis is elevated levels of a chemical called creatine kinase (CK). But many people experience pain and fatigue even though they have normal CK levels.4

Tahoe City resident Doug Peterson developed slurred speech, balance problems and severe fatigue after three years on Lipitor--for two and a half years, he had no side effects at all.5 It began with restless sleep patterns--twitching and flailing his arms. Loss of balance followed and the beginning of what Doug calls the "statin shuffle"--a slow, wobbly walk across the room. Fine motor skills suffered next. It took him five minutes to write four words, much of which was illegible. Cognitive function also declined. It was hard to convince his doctors that Lipitor could be the culprit, but when he finally stopped taking it, his coordination and memory improved.

John Altrocchi took Mevacor for three years without side effects; then he developed calf pain so severe he could hardly walk. He also experienced episodes of temporary memory loss.

For some, however, muscle problems show up shortly after treatment begins. Ed Ontiveros began having muscle problems within 30 days of taking Lipitor. He fell in the bathroom and had trouble getting up. The weakness subsided when he went off Lipitor. In another case, reported in the medical journal Heart, a patient developed rhabdomyolysis after a single dose of a statin.6 Heel pain from plantar fascitis (heel spurs) is another common complaint among those taking statin drugs. One correspondent reported the onset of pain in the feet shortly after beginning statin treatment. She had visited an evangelist, requesting that he pray for her sore feet. He enquired whether she was taking Lipitor. When she said yes, he told her that his feet had also hurt when he took Lipitor.7

Active people are much more likely to develop problems from statin use than those who are sedentary. In a study carried out in Austria, only six out of 22 athletes with familial hypercholesterolemia were able to endure statin treatment.8 The others discontinued treatment because of muscle pain.

By the way, other cholesterol-lowering agents besides statin drugs can cause joint pain and muscle weakness. A report in Southern Medical Journal described muscle pains and weakness in a man who took Chinese red rice, an herbal preparation that lowers cholesterol.9 Anyone suffering from myopathy, fibromyalgia, coordination problems and fatigue needs to look at low cholesterol plus Co-Q10 deficiency as a possible cause.

Neuropathy

Polyneuropathy, also known as peripheral neuropathy, is characterized by weakness, tingling and pain in the hands and feet as well as difficulty walking. Researchers who studied 500,000 residents of Denmark, about 9 percent of that country’s population, found that people who took statins were more likely to develop polyneuropathy.10 Taking statins for one year raised the risk of nerve damage by about 15 percent--about one case for every 2,200 patients. For those who took statins for two or more years, the additional risk rose to 26 percent.

According to the research of Dr. Golomb, nerve problems are a common side effect from statin use; patients who use statins for two or more years are at a four to 14-fold increased risk of developing idiopathic polyneuropathy compared to controls.11 She reports that in many cases, patients told her they had complained to their doctors about neurological problems, only to be assured that their symptoms could not be related to cholesterol-lowering medications.

The damage is often irreversible. People who take large doses for a long time may be left with permanent nerve damage, even after they stop taking the drug.

The question is, does widespread statin-induced neuropathy make our elderly drivers (and even not-so-elderly drivers) more accident prone? In July of 2003, an 86-year-old driver with an excellent driving record plowed into a farmers’ market in Santa Monica, California, killing 10 people. Several days later, a most interesting letter from a Lake Oswego, Oregon woman appeared in the Washington Post:12

"My husband, at age 68, backed into the garage and stepped on the gas, wrecking a lot of stuff. He said his foot slipped off the brake. He had health problems and is on medication, including a cholesterol drug, which is now known to cause problems with feeling in one’s legs.

"In my little community, older drivers have missed a turn and taken out the end of a music store, the double doors of the post office and the front of a bakery. In Portland, a bank had to do without its drive-up window for some time.

"It is easy to say that one’s foot slipped, but the problem could be lack of sensation. My husband’s sister-in-law thought her car was malfunctioning when it refused to go when a light turned green, until she looked down and saw that her food was on the brake. I have another friend who mentioned having no feeling in her lower extremities. She thought about having her car retrofitted with hand controls but opted for the handicapped bus instead."

Heart Failure

We are currently in the midst of a congestive heart failure epidemic in the United States--while the incidence of heart attack has declined slightly, an increase in the number heart failure cases has outpaced these gains. Deaths attributed to heart failure more than doubled from 1989 to 1997.13 (Statins were first given pre-market approval in 1987.) Interference with production of Co-Q10 by statin drugs is the most likely explanation. The heart is a muscle and it cannot work when deprived of Co-Q10.

Cardiologist Peter Langsjoen studied 20 patients with completely normal heart function. After six months on a low dose of 20 mg of Lipitor a day, two-thirds of the patients had abnormalities in the heart’s filling phase, when the muscle fills with blood. According to Langsjoen, this malfunction is due to Co-Q10 depletion. Without Co-Q10, the cell’s mitochondria are inhibited from producing energy, leading to muscle pain and weakness. The heart is especially susceptible because it uses so much energy.14

Co-Q10 depletion becomes more and more of a problem as the pharmaceutical industry encourages doctors to lower cholesterol levels in their patients by greater and greater amounts. Fifteen animal studies in six different animal species have documented statin-induced Co-Q10 depletion leading to decreased ATP production, increased injury from heart failure, skeletal muscle injury and increased mortality. Of the nine controlled trials on statin-induced Co-Q10 depletion in humans, eight showed significant Co-Q10 depletion leading to decline in left ventricular function and biochemical imbalances.15

Yet virtually all patients with heart failure are put on statin drugs, even if their cholesterol is already low. Of interest is a recent study indicating that patients with chronic heart failure benefit from having high levels of cholesterol rather than low. Researchers in Hull, UK followed 114 heart failure patients for at least 12 months.16 Survival was 78 percent at 12 months and 56 percent at 36 months. They found that for every point of decrease in serum cholesterol, there was a 36 percent increase in the risk of death within 3 years.

Dizziness

Dizziness is commonly associated with statin use, possibly due to pressure-lowering effects. One woman reported dizziness one half hour after taking Pravachol.17 When she stopped taking it, the dizziness cleared up. Blood pressure lowering has been reported with several statins in published studies. According to Dr. Golumb, who notes that dizziness is a common adverse effect, the elderly may be particularly sensitive to drops in blood pressure.18

Cognitive Impairment

The November 2003 issue of Smart Money19 describes the case of Mike Hope, owner of a successful ophthalmologic supply company: "There’s an awkward silence when you ask Mike Hope his age. He doesn’t change the subject or stammer, or make a silly joke about how he stopped counting at 21. He simply doesn’t remember. Ten seconds pass. Then 20. Finally an answer comes to him. ‘I’m 56,’ he says. Close, but not quite. ‘I will be 56 this year.’ Later, if you happen to ask him about the book he’s reading, you’ll hit another roadblock. He can’t recall the title, the author or the plot." Statin use since 1998 has caused his speech and memory to fade. He was forced to close his business and went on Social Security 10 years early. Things improved when he discontinued Lipitor in 2002, but he is far from complete recovery--he still cannot sustain a conversation. What Lipitor did was turn Mike Hope into an old man when he was in the prime of life.

Cases like Mike’s have shown up in the medical literature as well. An article in Pharmacotherapy, December 2003, for example, reports two cases of cognitive impairment associated with Lipitor and Zocor.20 Both patients suffered progressive cognitive decline that reversed completely within a month after discontinuation of the statins. A study conducted at the University of Pittsburgh showed that patients treated with statins for six months compared poorly with patients on a placebo in solving complex mazes, psychomotor skills and memory tests.21

Dr. Golomb has found that 15 percent of statin patients develop some cognitive side effects.22 The most harrowing involve global transient amnesia--complete memory loss for a brief or lengthy period--described by former astronaut Duane Graveline in his book Lipitor: Thief of Memory.23 Sufferers report baffling incidents involving complete loss of memory--arriving at a store and not remembering why they are there, unable to remember their name or the names of their loved ones, unable to find their way home in the car. These episodes occur suddenly and disappear just as suddenly. Graveline points out that we are all at risk when the general public is taking statins--do you want to be in an airplane when your pilot develops statin-induced amnesia?

While the pharmaceutical industry denies that statins can cause amnesia, memory loss has shown up in several statin trials. In a trial involving 2502 subjects, amnesia occurred in 7 receiving Lipitor; amnesia also occurred in 2 of 742 subjects during comparative trials with other statins. In addition, "abnormal thinking" was reported in 4 of the 2502 clinical trial subjects.24 The total recorded side effects was therefore 0.5 percent; a figure that likely under-represents the true frequency since memory loss was not specifically studied in these trials.

Cancer

In every study with rodents to date, statins have caused cancer.25 Why have we not seen such a dramatic correlation in human studies? Because cancer takes a long time to develop and most of the statin trials do not go on longer than two or three years. Still, in one trial, the CARE trial, breast cancer rates of those taking a statin went up 1500 percent.26 In the Heart Protection Study, non-melanoma skin cancer occurred in 243 patients treated with simvastatin compared with 202 cases in the control group.27

Manufacturers of statin drugs have recognized the fact that statins depress the immune system, an effect that can lead to cancer and infectious disease, recommending statin use for inflammatory arthritis and as an immune suppressor for transplant patients.28

Pancreatic Rot

The medical literature contains several reports of pancreatitis in patients taking statins. One paper describes the case of a 49-year-old woman who was admitted to the hospital with diarrhea and septic shock one month after beginning treatment with lovastatin.29 She died after prolonged hospitalization; the cause of death was necrotizing pancreatitis. Her doctors noted that the patient had no evidence of common risk factors for acute pancreatitis, such as biliary tract disease or alcohol use. "Prescribers of statins (particularly simvastatin and lovastatin) should take into account the possibility of acute pancreatitis in patients who develop abdominal pain within the first weeks of treatment with these drugs," they warned.

Depression

Numerous studies have linked low cholesterol with depression. One of the most recent found that women with low cholesterol are twice as likely to suffer from depression and anxiety. Researchers from Duke University Medical Center carried out personality trait measurements on 121 young women aged 18 to 27.30 They found that 39 percent of the women with low cholesterol levels scored high on personality traits that signalled proneness to depression, compared to 19 percent of women with normal or high levels of cholesterol. In addition, one in three of the women with low cholesterol levels scored high on anxiety indicators, compared to 21 percent with normal levels. Yet the author of the study, Dr. Edward Suarez, cautioned women with low cholesterol against eating "foods such as cream cakes" to raise cholesterol, warning that these types of food "can cause heart disease." In previous studies on men, Dr. Suarez found that men who lower their cholesterol levels with medication have increased rates of suicide and violent death, leading the researchers to theorize "that low cholesterol levels were causing mood disturbances."

How many elderly statin-takers eke through their golden years feeling miserable and depressed, when they should be enjoying their grandchildren and looking back with pride on their accomplishments? But that is the new dogma--you may have a long life as long as it is experienced as a vale of tears.

Any Benefits?

Most doctors are convinced--and seek to convince their patients--that the benefits of statin drugs far outweigh the side effects. They can cite a number of studies in which statin use has lowered the number of coronary deaths compared to controls. But as Dr. Ravnskov has pointed out in his book The Cholesterol Myths,31 the results of the major studies up to the year 2000--the 4S, WOSCOPS, CARE, AFCAPS and LIPID studies--generally showed only small differences and these differences were often statistically insignificant and independent of the amount of cholesterol lowering achieved. In two studies, EXCEL, and FACAPT/TexCAPS, more deaths occurred in the treatment group compared to controls. Dr. Ravnskov’s 1992 meta-analysis of 26 controlled cholesterol-lowering trials found an equal number of cardiovascular deaths in the treatment and control groups and a greater number of total deaths in the treatment groups.32 An analysis of all the big controlled trials reported before 2000 found that long-term use of statins for primary prevention of heart disase produced a 1 percent greater risk of death over 10 years compared to a placebo.33

Recently published studies do not provide any more justification for the current campaign to put as many people as possible on statin drugs.

Honolulu Heart Program (2001)

This report, part of an ongoing study, looked at cholesterol lowering in the elderly. Researchers compared changes in cholesterol concentrations over 20 years with all-cause mortality.34 To quote: "Our data accords with previous findings of increased mortality in elderly people with low serum cholesterol, and show that long-term persistence of low cholesterol concentration actually increases risk of death. Thus, the earlier that patients start to have lower cholesterol concentrations, the greater the risk of death. . . The most striking findings were related to changes in cholesterol between examination three (1971-74) and examination four (1991-93). There are few studies that have cholesterol concentrations from the same patients at both middle age and old age. Although our results lend support to previous findings that low serum cholesterol imparts a poor outlook when compared with higher concentrations of cholesterol in elderly people, our data also suggest that those individuals with a low serum cholesterol maintained over a 20-year period will have the worst outlook for all-cause mortality [emphasis ours]."

MIRACL (2001)

The MIRACL study looked at the effects of a high dose of Lipitor on 3086 patients in the hospital after angina or nonfatal MI and followed them for 16 weeks.35 According to the abstract: "For patients with acute coronary syndrome, lipid-lowering therapy with atorvastatin, 80 mg/day, reduced recurrent ischemic events in the first 16 weeks, mostly recurrent symptomatic ischemia requiring rehospitalization." What the abstract did not mention was that there was no change in death rate compared to controls and no significant change in re-infarction rate or need for resuscitation from cardiac arrest. The only change was a significant drop in chest pain requiring rehospitalization.

ALLHAT (2002)

ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), the largest North American cholesterol-lowering trial ever and the largest trial in the world using Lipitor, showed mortality of the treatment group and controls after 3 or 6 years was identical.36 Researchers used data from more than 10,000 participants and followed them over a period of four years, comparing the use of a statin drug to "usual care," namely maintaining proper body weight, no smoking, regular exercise, etc., in treating subjects with moderately high levels of LDL cholesterol. Of the 5170 subjects in the group that received statin drugs, 28 percent lowered their LDL cholesterol significantly. And of the 5185 usual-care subjects, about 11 percent had a similar drop in LDL. But both groups showed the same rates of death, heart attack and heart disease.

Heart Protection Study (2002)

Carried out at Oxford University,37 this study received widespread press coverage; researchers claimed "massive benefits" from cholesterol-lowering,38 leading one commentator to predict that statin drugs were "the new aspirin."39 But as Dr. Ravnskov points out,40 the benefits were far from massive. Those who took simvastatin had an 87.1 percent survival rate after five years compared to an 85.4 percent survival rate for the controls and these results were independent of the amount of cholesterol lowering. The authors of the Heart Protection Study never published cumulative mortality data, even though they received many requests to do so and even though they received funding and carried out a study to look at cumulative data. According to the authors, providing year-by-year mortality data would be an "inappropriate" way of publishing their study results.41

PROSPER (2002)

PROSPER (Prospective Study of Pravastatin in the Elderly at Risk) studied the effect of pravastatin compared to placebo in two older populations of patients of which 56 percent were primary prevention cases (no past or symptomatic cardiovascular disease) and 44 percent were secondary prevention cases (past or symptomatic cardiovascular disease).42 Pravastatin did not reduce total myocardial infarction or total stroke in the primary prevention population but did so in the secondary. However, measures of overall health impact in the combined populations, total mortality and total serious adverse events were unchanged by pravastatin as compared to the placebo and those in the treatment group had increased cancer. In other words: not one life saved.

J-LIT (2002)

Japanese Lipid Intervention Trial was a 6-year study of 47,294 patients treated with the same dose of simvastatin.43 Patients were grouped by the amount of cholesterol lowering. Some patient had no reduction in LDL levels, some had a moderate fall in LDL and some had very large LDL reductions. The results: no correlation between the amount of LDL lowering and death rate at five years. Those with LDL cholesterol lower than 80 had a death rate of just over 3.5 at five years; those whose LDL was over 200 had a death rate of just over 3.5 at five years.

Meta-Analysis (2003)

In a meta-analysis of 44 trials involving almost 10,000 patients, the death rate was identical at 1 percent of patients in each of the three groups--those taking atorvastatin (Lipitor), those taking other statins and those taking nothing.44 Furthermore, 65 percent of those on treatment versus 45 percent of the controls experienced an adverse event. Researchers claimed that the incidence of adverse effects was the same in all three groups, but 3 percent of the atorvastatin-treated patients and 4 percent of those receiving other statins withdrew due to treatment-associated adverse events, compared with 1 percent of patients on the placebo.

Statins and Plaque (2003)

A study published in the American Journal of Cardiology casts serious doubts on the commonly held belief that lowering your LDL-cholesterol, the so-called bad cholesterol, is the most effective way to reduced arterial plaque.45 Researchers at Beth Israel Medical Center in New York City examined the coronary plaque buildup in 182 subjects who took statin drugs to lower cholesterol levels. One group of subjects used the drug aggressively (more than 80 mg per day) while the balance of the subjects took less than 80 mg per day. Using electron beam tomography, the researchers measured plaque in all of the subjects before and after a study period of more than one year. The subjects were generally successful in lowering their cholesterol, but in the end there was no statistical difference in the two groups in the progression of arterial calcified plaque. On average, subjects in both groups showed a 9.2 percent increase in plaque buildup.

Statins and Women (2003)

No study has shown a significant reduction in mortality in women treated with statins. The University of British Columbia Therapeutics Initiative came to the same conclusion, with the finding that statins offer no benefit to women for prevention of heart disease.46 Yet in February of 2004, Circulation published an article in which more than 20 organizations endorsed cardiovascular disease prevention guidelines for women with several mentions of "preferably a statin."47

ASCOT-LLA (2003)

ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm) was designed to assess the benefits of atorvastatin (Lipitor) versus a placebo in patients who had high blood pressure with average or lower-than-average cholesterol concentrations and at least three other cardiovascular risk factors.48 The trial was originally planned for five years but was stopped after a median follow-up of 3.3 years because of a significant reduction in cardiac events. Lipitor did reduce total myocardial infarction and total stroke; however, total mortality was not significantly reduced. In fact, women were worse off with treatment. The trial report stated that total serious adverse events "did not differ between patients assigned atorvastatin or placebo," but did not supply the actual numbers of serious events.

Cholesterol Levels in Dialysis Patients (2004)

In a study of dialysis patients, those with higher cholesterol levels had lower mortality than those with low cholesterol.49 Yet the authors claimed that the "inverse association of total cholesterol level with mortality in dialysis patients is likely due to the cholesterol-lowering effect of systemic inflammation and malnutrition, not to a protective effect of high cholesterol concentrations." Keeping an eye on further funding opportunities, the authors concluded: "These findings support treatment of hypercholesterolemia in this population."

PROVE-IT (2004)

PROVE-IT (PRavastatin Or AtorVastatin Evaluation and Infection Study),50 led by researchers at Harvard University Medical School, attracted immense media attention. "Study of Two Cholesterol Drugs Finds One Halts Heart Disease," was the headline in the New York Times.51 In an editorial entitled "Extra-Low Cholesterol," the paper predicted that "The findings could certainly presage a significant change in the way heart disease patients are treated. It should also start a careful evaluation of whether normally healthy people could benefit from a sharp drug-induced reduction in their cholesterol levels."52

The Washington Post was even more effusive, with a headline "Striking Benefits Found in Ultra-Low Cholesterol."53 "Heart patients who achieved ultra-low cholesterol levels in one study were 16 percent less likely to get sicker or to die than those who hit what are usually considered optimal levels. The findings should prompt doctors to give much higher doses of drugs known as statins to hundreds of thousands of patients who already have severe heart problems, experts said. In addition, it will probably encourage physicians to start giving the medications to millions of healthy people who are not yet on them, and to boost dosages for some of those already taking them to lower their cholesterol even more, they said."

The study compared two statin drugs, Lipitor and Pravachol. Although Bristol Myers-Squibb (BMS), makers of Pravachol, sponsored the study, Lipitor (made by Pfizer) outperformed its rival Pravachol in lowering LDL. The "striking benefit" was a 22 percent rate of death or further adverse coronary events in the Lipitor patients compared to 26 percent in the Pravachol patients.

PROVE-IT investigators took 4162 patient who had been in the hospital following an MI or unstable angina. Half got Pravachol and half got Lipitor. Those taking Lipitor had the greatest reduction of LDL-cholesterol--LDL in the Pravachol group was 95, in the Lipitor group it was 62--a 32 percent greater reduction in LDL levels and a 16 percent reduction in all-cause mortality. But that 16 percent was a reduction in relative risk. As pointed out by Red Flags Daily columnist Dr. Malcolm Kendrick, the absolute reduction in the rate of the death rate of those taking Lipitor rather than Pravachol, was one percent, a decrease from 3.2 percent to 2.2 percent over 2 years.54 Or, to put it another way, a 0.5 percent absolute risk reduction per year--these were the figures that launched the massive campaign for cholesterol-lowering in people with no risk factors for heart disease, not even high cholesterol.

And the study was seriously flawed with what Kendrick calls "the two-variables conundrum." "It is true that those with the greatest LDL lowering were protected against death. However, . . . those who were protected not only had a greater degree of LDL lowering, they were also on a different drug! which is rather important, yet seems to have been swept aside on a wave of hype. If you really want to prove that the more you lower the LDL level, the greater the protection, then you must use the same drug. This achieves the absolutely critical requirement of any scientific experiment, which is to remove all possible uncontrolled variables. . . As this study presently stands, because they used different drugs, anyone can make the case that the benefits seen in the patients on atorvastatin [Lipitor] had nothing to do with greater LDL lowering; they were purely due to the direct drug effects of atorvastatin." Kendrick notes that the carefully constructed J-LIT study, published 2 years earlier, found no correlation whatsoever between the amount of LDL lowering and death rate. This study had ten times as many patients, lasted almost three times as long and used the same drug at the same dose in all patients. Not surprisingly, J-LIT attracted virtually no media attention.

PROVE-IT did not look at side effects but Dr. Andrew G. Bodnar, senior vice president for strategy and medical and external affairs at Bristol Meyer Squibb, makers of the losing statin, indicated that liver enzymes were elevated in 3.3 percent of the Lipitor group but only in 1.1 percent of the Pravachol group, noting that when liver enzyme levels rise, patients must be advised to stop taking the drug or reduce the dose.55 And withdrawal rates were very high: thirty-three percent of patients discontinued Pravachol and 30 percent discontinued Lipitor after two years due to adverse events or other reasons.56

REVERSAL (2004)

In a similar study, carried out at the Cleveland Clinic, patients were given either Lipitor or Pravachol. Those receiving Lipitor achieved much lower LDL-cholesterol levels and a reversal in "the progression of coronary plaque aggregation."57 Those who took Lipitor had plaque reduced by 0.4 percent over 18 months, based on intravascular ultrasound (not the more accurate tool of electron beam tomography); Dr. Eric Topol of the Cleveland Clinic claimed these decidedly unspectacular results "Herald a shake-up in the field of cardiovascular prevention.. . . the implications of this turning point--that is, of the new era of intensive statin therapy--are profound. Even today, only a fraction of the patients who should be treated with a statin are actually receiving such therapy. . . More than 200 million people worldwide meet the criteria for treatment, but fewer than 25 million take statins."58 Not surprisingly, an article in The Wall Street Journal noted "Lipitor Prescriptions Surge in Wake of Big Study."59

But as Dr. Ravnskov points out, the investigators looked at change in atheroma volume, not the change in lumen area, "a more important parameter because it determines the amount of blood that can be delivered to the myocardium. Change of atheroma volume cannot be translated to clinical events because adaptive mechansims try to maintain a normal lumen area during early atherogenesis."60

Other Uses

With such paltry evidence of benefit, statin drugs hardly merit the hyperbole heaped upon them. Yet the industry maintains a full court press, urging their use for greater and greater numbers of people, not only for cholesterol lowering but also as treatment for other diseases--cancer, multiple sclerosis, osteoporosis, stroke, macular degeneration, arthritis and even mental disorders such as memory and learning problems, Alzheimers and dementia.61 New guidelines published by the American College of Physicians call for statin use by all people with diabetes older than 55 and for younger diabetes patients who have any other risk factor for heart disease, such as high blood pressure or a history of smoking.62 David A. Drachman, professor of neurology at the University of Massachusetts Medical School calls statins "Viagra for the brain."63 Other medical writers have heralded the polypill, composed of a statin drug mixed with a blood pressure medication, aspirin and niacin, as a prevent-all that everyone can take. The industry is also seeking the right to sell statins over the counter.

Can honest assessment find any possible use for these dangerous drugs? Dr. Peter Langsjoen of Tyler, Texas, suggests that statin drugs are appropriate only as a treatment for cases of advanced Cholesterol Neurosis, created by the industry’s anti-cholesterol propaganda. If you are concerned about your cholesterol, a statin drug will relieve you of your worries.

Creative Advertising

The best advertising for statin drugs is free front-page coverage following gushy press releases. But not everyone reads the paper or goes in for regular medical exams, so statin manufacturers pay big money for creative ways to create new users. For example, a new health awareness group called the Boomer Coalition supported ABC’s Academy Awards telecast in March of 2004 with a 30-second spot flashing nostalgic images of celebrities lost to cardiovascular disease--actor James Coburn, baseball star Don Drysdale and comedian Redd Foxx. While the Boomer Coalition sounds like a grass roots group of health activists, it is actually a creation of Pfizer, manufacturers of Lipitor. "We’re always looking for creative ways to break through what we’ve found to be a lack of awareness and action," says Michal Fishman, a Pfizer spokeswoman. "We’re always looking for what people really think and what’s going to make people take action," adding that there is a stigma about seeking treatment and many people "wrongly assume that if they are physically fit, they aren’t at risk for heart disease."64 The Boomer Coalition website allows visitors to "sign up and take responsibility for your heart health," by providing a user name, age, email address and blood pressure and cholesterol level.

A television ad in Canada admonished viewers to "Ask your doctor about the Heart Protection Study from Oxford University." The ad did not urge viewers to ask their doctors about EXCEL, ALLHAT, ASCOT, MIRACL or PROSPER, studies that showed no benefit--and the potential for great harm--from taking statin drugs.

The Costs

Statin drugs are very expensive--a course of statins for a year costs between $900 and $1400. They constitute the mostly widely sold pharmaceutical drug, accounting for 6.5 percent of market share and 12.5 billion dollars in revenue for the industry. Your insurance company may pay most of that cost, but consumers always ultimately pay with higher insurance premiums. Payment for statin drugs poses a huge burden for Medicare, so much so that funds may not be available for truly lifesaving medical measures.

In the UK, according to the National Health Service, doctors wrote 31 million prescriptions for statins in 2003, up from 1 million in 1995 at a cost of 7 billion pounds--and that’s just in one tiny island.65 In the US, statins currently bring in $12.5 billion annually for the pharmaceutical industry. Sales of Lipitor, the number-one-selling statin, are projected to hit $10 billion in 2005.

REFERENCES

1. Hoffman G. N Engl J Med 1986;314:1610-24

2. Eleanor Laise. The Lipitor Dilemma, Smart Money: The Wall Street Journal Magazine of Personal Business, November 2003.

3. Eleanor Laise. The Lipitor Dilemma, Smart Money: The Wall Street Journal Magazine of Personal Business, November 2003.

4. Beatrice A. Golomb, MD, PhD on Statin Drugs, March 7, 2002. www.coloradohealthsite.org/topics/interviews/golomb.html

5. Melissa Siig. Life After Lipitor: Is Pfizer product a quick fix or dangerous drug? Residents experience adverse reactions. Tahoe World, January 29, 2004.

6. Jamil S, Iqbal P. Heart 2004 Jan;90(1):e3.

7. Personal communication, Laura Cooper, May 1, 2003.

8. Sinzinger H, O’Grady J. Br J Clin Pharmacol. 2004 Apr;57(4):525-8.

9. Smith DJ and Olive KE. Southern Medical Journal 96(12):1265-1267, December 2003.

10. Gaist D and others. Neurology 2002 May 14;58(9):1321-2.

11. Statins and the Risk of Polyneuropathy. http://coloradohealthsite.org/CHNReports/statins_polyneuropathy.html

12. The Struggles of Older Drivers, letter by Elizabeth Scherdt. Washington Post, June 21, 2003.

13. Langsjoen PH. The clinical use of HMG Co-A reductase inhibitors (statins) and the associated depletion of the essential co-factor coenzyme Q10: a review of pertinent human and animal data. http://www.fda.gov/ohrms/dockets/dailys/02/May02/052902/02p-0244-cp00001-02-Exhibit_A-vol1.pdf

14. Eleanor Laise. The Lipitor Dilemma, Smart Money: The Wall Street Journal Magazine of Personal Business, November 2003.

15. Langsjoen PH. The clinical use of HMG Co-A reductase inhibitors (statins) and the associated depletion of the essential co-factor coenzyme Q10: a review of pertinent human and animal data. http://www.fda.gov/ohrms/dockets/dailys/02/May02/052902/02p-0244-cp00001-02-Exhibit_A-vol1.pdf

16. Clark AL and others. J Am Coll Cardiol 2003;42:1933-1943.

17. Personal communication, Jason DuPont, MD, July 7, 2003

18. Sandra G Boodman. Statins’ Nerve Problems. Washington Post, September 3, 2002.

19. Eleanor Laise. The Lipitor Dilemma, Smart Money: The Wall Street Journal Magazine of Personal Business, November 2003,

20. King, DS. Pharmacotherapy 25(12):1663-7, Dec, 2003.

21. Muldoon MF and others. Am J Med 2000 May;108(7):538-46.

22. Email communication, Beatrice Golomb, July 10, 2003.

23. Duane Graveline, MD. Lipitor: Thief of Memory, 2004, http://www.buybooksontheweb.com/.

24. Lopena OF. Pharm D, Pfizer, Inc., written communication, 2002. Quoted in an email communication from Duane Graveline, spacedoc@webtv.net

25. Newman TB, Hulley SB. JAMA 1996;27:55-60

26. Sacks FM and others. N Eng J Med 1996;385;1001-1009.

27. Heart Protection Study Collaborative Group. Lancet 2002;360:7-22.

28. Leung BP and others. J Immunol. Feb 2003 170(3);1524-30; Palinski W. Nature Medicine Dec 2000 6;1311-1312.

29. J Pharm Technol 2003;19:283-286.

30. Low Cholesterol Linked to Depression. BBC Online Network, May 25,1999.

31. Uffe Ravnskov, MD, PhD. The Cholesterol Myths. NewTrends Publishing, 2000.

32. Ravnskov U. BMJ. 1992;305:15-19.

33. Jackson PR. Br J Clin Pharmacol 2001;52:439-46.

34. Schatz IJ and others. Lancet 2001 Aug 4;358:351-355.

35. Schwartz GG and others. J Am Med Assoc. 2001;285:1711-8.

36. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. JAMA 2002;288:2998-3007.

37. Heart Protection Study Collaborative Group. Lancet 2002;360:7-22.

38. Medical Research Council/British Heart Foundation Heart Protection Study.Press release. Life-saver: World’s largest cholesterol-lowering trial reveals massive benefits for high-risk patients. Available at www.ctsu.ox.ac.uk/~hps/pr.shtml.

39. Kmietowicz A. BMJ 2001;323:1145

40. Ravnskov U. BMJ 2002;324:789

41. Email communication, Eddie Vos, February 13, 2004 and posted at www.health-heart.org/comments.htm#PetoCollins.

42. Shepherd J and others. Lancet 2002;360:1623-1630.

43. Matsuzaki M and others. Circ J. 2002 Dec;66(12):1087-95.

44. Hecht HS, Harmon SM. Am J Cardiol 2003; 92:670-676

45. Hecht HS and others. Am J Cardiol 2003;92:334-336

46. Jenkins AJ. BMJ 2003 Oct 18;327(7420):933.

47. Circulation, 2004 Feb 17;109(6):714-21.

48. Sever PS and others. Lancet 2003;361:1149-1158.

49. Liu Y and others. JAMA 2004;291:451-459.

50. Cannon CP and others. N Engl J Med 2004 Apr 8;350(15):1495-504. Epub 2004 Mar 08.

51. Gina Kolata. Study of Two Cholesterol Drugs Finds One Halts Heart Disease. The New York Times, November 13, 2003.

52. Extra-Low Cholesterol, The New York Times, March 10, 2003

53. Rob Stein. Striking Benefits Found in Ultra-Low Cholesterol, The Washington Post, March 9, 2004

54. Dr. Malcolm Kendrick. PROVE IT- PROVE WHAT? http://www.redflagsweekly.com/applications/ui/login.php?Next=/kendrick/2004_mar10.php&e=4

55. Health Sciences Institute e-alert, www.hsibaltimore.com, March 11, 2004

56. Email communication, Joel Kauffman, April 15, 2004.

57. Nissen SE and others. JAMA 2004 Mar 3;291(9):1071-80.

58. Dr. Malcolm Kendrick. PROVE IT- PROVE WHAT? http://www.redflagsweekly.com/applications/ui/login.php?Next=/kendrick/2004_mar10.php&e=4

59. Scott Hensley. The Statin Dilemma: How Sluggish Sales Hurt Merck, Pfizer. The Wall Street Journal, July 25, 2003.

60. Ravnskov, U. Unpublished letter. ravnskov@tele2.se .

61. Cholesterol--And Beyond: Statin Drugs Have Cut Heart Disease. Now They Show Promise Against Alzheimer’s, Multiple Sclerosis & Osteoporosis. Newsweek, July 14. 2003.

62. John O’Neil. Treatments: Statins and Diabetes: New Advice. New York Times, April 20, 2004.

63. Peter Jaret. Statins’ Burst of Benefits. Los Angeles Times, July 2. 2003.

64. Behind the ‘Boomer Coalition,’ A Heart Message from Pfizer, Wall Street Journal, March 10, 2004

65. Paul J. Fallon, personal communication, March, 2004.

66. Uffe Ravnskov, MD, PhD. The Cholesterol Myths. NewTrends Publishing, 2000, pp 208-210.

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