Frequently Asked Questions about Statin Adverse Effects (sorry if duplicate, first post attempt did not appear)
What are the names of the Statin drugs?
The Cholesterol-lowering Statin Drug Names: Lipitor, Mevacor, Pravachol,
Zocor, Lescol, Crestor and Baycol, aka atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin; This class of drugs is also known as HMG-CoA Reductase Inhibitors, short for
3-Hydroxy-3-Methyl-Glutaryl Coenzyme A Reductase.
http://www.bms.com/cgi-bin/anybin.pl?sql=select%20PPI%
0A%09%09%09%09%20%20%20from%20TB_PRODUCT_PPI%20%0A%09%
09%09%09%20%20%20where%20PPI_SEQ%20=%2056&key=PPI
http://www.ca.pharma.novartis.com/downloads/e/
lescol_scrip_e.pdf
http://www.merck.com/product/usa/pi_circulars/m/
mevacor/mevacor_pi.pdf
http://www.merck.com/product/usa/pi_circulars/z/zocor/
zocor_pi.pdf
Where can I look to find information on research studies of statin drugs?
The National Institutes of Health has a website,
http://www.ncbi.nlm.nih.gov/Entrez/ that offers a search engine that is useful in finding the latest studies that have been published in medical journals (over 11,000,000 biomedical journal citations) and other major repositories of medical research. Each study usually comes with an Abstract, or summary of the findings. In most cases, should you want to see the full text of the study, the full article can be purchased online for approximately $25 to $40, depending on the journal, which is much cheaper than a subscription.
Note that journals publish new studies every month, so revisit the site often. Also, if you find a study that is pertinent to what you are looking for, check the links to the right that will take you to similar studies on the same topic. Finally, if you don't get a 'hit' on what you are looking for, try medical terminology synonyms. Search results are different when using different search terms. So, for example: "statin" or "atorvastatin" or
"lipitor" or "reductase inhibitor" or "HMG-CoA". Similarly, "cholesterol" will return different results from "Dyslipidemia."
Why does my physician have such a difficult time believing that my physical problems might be an adverse effect of Lipitor or one of the other statins?
Statins are now the most widely prescribed of all prescription drugs, making them very big business. The Wall Street Journal Online, in a June 13, 2003 article, "As Drug Sales Teams Multiply, Doctors Start to Tune them Out;
'Arms Race' by Pfizer and Rivals Boosts Pill Prices, Ire, but No One Dares
Retreat", reported that Pfizer's sales of Lipitor alone were $8 BILLION for the year 2002. That is just for Lipitor alone, one of FIVE statins on the market today. The article states that in 2002 the drug companies spent over $12 Billion on their sales forces. According to the article, "Last year, a few Pfizer reps brought along a guest speaker who was both a doctor and lawyer to a lunch meeting with doctors at Clinical Associates, a group practice in suburban Baltimore. He said they risked being sued if their patients didn't reach their cholesterol goals". Doctors are the ones who are primarily targeted by the advertising blitz to make the expectations of increased sales come true. In addition, consumers are marketed with slick commercials and ads. Doctors are very busy, and they are inundated with positive statin spin. They may think that, since everyone is taking it, if there were problems they would have heard about it. They may not take the time to dig out negative information, and there are no major sponsors to fund equal time for negative reports.
Only last year, in 2002, did the Journal of the American Medical Association begin annotating publications with the author's ties to the company studied, citing potential conflict of interest.
The British Journal of Medicine in their May 31, 2003 issue on the theme
"Time to untangle doctors from drug companies", ran no less than 6 articles saying that too many of the published drug studies are no more than industry-sponsored infomercials, and cited the selective reporting bias whereby only pro-industry studies are published. These articles were entitled: "Research sponsored by drug companies is biased"; " Drug representatives may increase unnecessary GP prescribing"; "Reporting of clinical trials of drugs shows bias"; "Characteristics of General
Practicioners who Frequently see Drug Industry Representatives: National
Cross-Sectional Study "; "No more free lunches; Patients will benefit from doctors and drug companies disentangling"; "Information from drug companies and opinion leaders; Double standards in information for medical journals and practitioners should go"
http://bmj.com/content/vol326/issue7400/
on the prevalent problem of medical ghostwriting. In this scheme, drug companies write a study favorable to their product and then "reward" a doctor who prescribes the drug by listing his name as the "author" in the publication.
http://www.cbc.ca/consumers/market/files/health/
ghostwriting/links.html
Your physician should look into your physical adverse effects, regardless of suspected cause. Do not permit your physician to put you off when you express a concern. Too many people are reporting long-term, perhaps permanent, damage when statin therapy is continued despite the appearance of adverse effects. In some cases, like rhabdomyolysis, death results. Oddly, people consistently report doctors who are dubious of reported problems being due to statins, even when the problem is listed by the manufacturer on the Physicians' Information page for the drug. It may help, if you identify your problems with the findings of a published study, to print out a copy and bring it with you to the doctor's appointment.
In the popular press, Smart Money magazine (November 2003 issue) has an excellent article by Eleanore Laise on people disabled by statin adverse effects, and what expert doctors are researching to help.
That is one of the purposes for this FAQ - to give people an additional tool help them to communicate with their doctors.
Note: These articles documenting or speculating on adverse effects of statins are in the vast minority. Hundreds, even thousands, of articles and research have praised statins. Certainly the people with side effects are in the minority, and the benefits are fantastic. Still, the doctors who do attempt to publish about problems associated with statins are often very bitter: they feel they are up against a tremendous political bias and going against an incredibly powerful industry. Med Journal editors tend to insist that all negative findings be couched in terms of how, overall, the statins are doing tremendous good, and the major studies finding problems with statins have been the subject of a pro-statin editorial in the same journal.
Further, the popular press is extremely reluctant to cover negative research findings for the companies who are among their heaviest advertisers.
Two recent examples of bias in the presentation of pivotal findings are:
1) Dr. Gaist's study that proves statins cause polyneuropathy
http://213.4.18.135/87.pdf. If you read the entire research article, you will note the vast difference between his findings and the tone of the descriptive abstract, that tends to water down the findings. Further, the journal ran an editorial that provided further pro-statin spin as damage control.
2) The ALLHAT study, published in JAMA, was the largest to date. It ran for years and encompassed 10,000 people. Their study website
http://allhat.sph.uth.tmc.edu/default.htm These folks were funded by NIH, and they have published what the drug companies do not want to hear: that statins do not prevent deaths. Again, there was a pro-statin damage control
findings. In fact, CNN buried it inside an article on the other finding:
that diuretics worked better than other blood-pressure medications, where no reader looking for cholesterol drug results would find it.
OK, I understand the doctor's need to read clinical study results, but where can I find out what other people are experiencing in plain language, and maybe share my experiences?
The Dispace statin boards are an excellent source:
Lipitor:
http://forum.ditonline.com/viewboard.php?BoardID=38
Zocor:
http://forum.ditonline.com/viewboard.php?BoardID=41
Lescol:
http://forum.ditonline.com/viewboard.php?BoardID=37
Pravachol:
http://forum.ditonline.com/viewboard.php?BoardID=40
Mevacor:
http://forum.ditonline.com/viewboard.php?BoardID=39
AARP ran an article on statin drugs and asked for responses, these posts start at:
http://community.aarp.org/n/mb/message.asp?webtag=rp-
health&msg=743.1 (at the bottom of the page, you can click to the next post)
Another board:
http://www.rxlist.com/rxboard/lipitor.pl
http://www.rxlist.com/rxboard/lescol.pl
http://www.rxlist.com/rxboard/mevacor.pl
http://www.rxlist.com/rxboard/pravachol.pl
http://www.rxlist.com/rxboard/zocor.pl
WebMD has a roundtable on Cholesterol:
http://boards.webmd.com/roundtable_topic/1121
sci.med.cardiology
Dr. Graveline, retired family MD, USAF Flight Surgeon, researcher in space medicine and US Astronaut, who suffered adverse effects from Lipitor, maintains several websites and has written on a book about statin-related memory loss and amnesia, Lipitor, Thief of Memory, at:
www.spacedoc.net (you can start here and read about his life and his books)
http://www.spacedoc.net/lipitor_thief_of_memory.html
http://www.spacedoc.net/lipitor.htm
http://www.spacedoc.net/statin_dialogues.htm
What are the Liptior warnings and side-effects listed by the manufacturer on the physicians' information?
For a full introduction to the list, view
http://www.lipitor.com/pi/default.asp . Summary of some of the items on the website includes Warnings of liver dysfunction, and skeletal muscle rhabdomyolysis for the physicians information updated as of April 2002.
What are the Lipitor Adverse Events in Placebo-Controlled Studies listed by
Pfizer in the Physician's information?
For a full introduction to the list, view
http://www.lipitor.com/pi/default.asp, the information below is from the version updated as of April 2002:
Body as a whole: Infection, Headache, Accidental Injury, Flu Syndrome,
Abdominal Pain, Back Pain, Allergic Reaction, Asthenia;
Digestive system: Constipation, Diarrhea, Dyspepsia, Flatulence;
Respiratory system: Sinusitis, Pharyngitis;
Skin and Appendages: Rash;
Musculoskeletal system: Arthralgia, Myalgia.
What are the Lipitor Averse Events reported in patients treated with Lipitor in clinical trials listed by Pfizer in the Physician's information?
For a full introduction to the list, view
http://www.lipitor.com/pi/default.asp, the information below is from the version updated as of April 2002:
Body as a Whole: Chest pain, face edema, fever, neck rigidity, malaise, photosensitivity reaction, generalized edema.
Digestive System: Nausea, gastroenteritis, liver function tests abnormal, colitis, vomiting, gastritis, dry mouth, rectal hemorrhage, esophagitis, eructation, glossitis, mouth ulceration, anorexia, increased appetite, stomatitis, biliary pain, cheilitis, duodenal ulcer, dysphagia, enteritis, melena, gum hemorrhage, stomach ulcer, tenesmus, ulcerative stomatitis, hepatitis, pancreatitis, cholestatic jaundice.
Respiratory System: Bronchitis, rhinitis, pneumonia, dyspnea, asthma, epistaxis.
Nervous System: Insomnia, dizziness, paresthesia, somnolence, amnesia, abnormal dreams, libido decreased, emotional lability, incoordination, peripheral neuropathy, torticollis, facial paralysis, hyperkinesia, depression, hypesthesia, hypertonia.
Musculoskeletal System: Arthritis, leg cramps, bursitis, tenosynovitis, myasthenia, tendinous contracture, myositis.
Skin and Appendages: Pruritus, contact dermatitis, alopecia, dry skin, sweating, acne, urticaria, eczema, seborrhea, skin ulcer.
Urogenital System: Urinary tract infection, urinary frequency, cystitis, hematuria, impotence, dysuria, kidney calculus, nocturia, epididymitis, fibrocystic breast, vaginal hemorrhage, albuminuria, breast enlargement, metrorrhagia, nephritis, urinary incontinence, urinary retention, urinary urgency, abnormal ejaculation, uterine hemorrhage.
Special Senses: Amblyopia, tinnitus, dry eyes, refraction disorder, eye hemorrhage, deafness, glaucoma, parosmia, taste loss, taste perversion.
Cardiovascular System: Palpitation, vasodilatation, syncope, migraine, postural hypotension, phlebitis, arrhythmia, angina pectoris, hypertension.
Metabolic and Nutritional Disorders: Peripheral edema, hyperglycemia, creatine phosphokinase increased, gout, weight gain, hypoglycemia.
Hemic and Lymphatic System: Ecchymosis, anemia, lymphadenopathy, thrombocytopenia, petechia.
What are the Lipitor Adverse events associated with Lipitor therapy reported since market introduction, that are not listed above, listed by Pfizer in the Physician's information?
For a full introduction to the list, view
http://www.lipitor.com/pi/default.asp, the information below is from the version updated as of April 2002:
anaphylaxis, angioneurotic edema, bullous rashes (including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis), and rhabdomyolysis.
What does Public Citizen say about the new statin, Crestor?
http://www.citizen.org/pressroom/release.cfm?ID=1543 also
"Public Citizen Warns Against New Statin Drug Crestor," September 16, 2003.
"Patients should not take the newly approved cholesterol drug, rosuvastatin, which AstraZeneca will sell under the name Crestor, because it has a significant potential to cause kidney damage and failure, as well as muscle destruction, Public Citizen's Health Research Group said today."
REPORTING ADVERSE EFFECTS FROM STATINS
Where should I report adverse effects from statins?
Report to the FDA,
http://www.fda.gov/medwatch/how.htm
Also, it is important to report side-effects to the Statin Study, funded by the National Institutes of Health and conducted at the University of
California, San Diego.
Statin Study website:
http://medicine.ucsd.edu/statin/ with contact info at:
http://medicine.ucsd.edu/statin/contactinfo.html
MAILING ADDRESS: UCSD Statin Study 9500 Gilman Dr. La Jolla, CA 92093-0995
PHONE NUMBER: (858 558-4950
Dr. Golomb, the principal investigator of the Statin Study, is an incredibly intelligent and active woman. Take a look at her Curriculum Vitae at:
http://www.medicine.ucsd.edu/faculty/golomb/
NERVE DAMAGE & STATINS
Frequently Asked Question: What medical research studies have been done on
Statins and Nerve Damage that I can bring to my doctor's attention?
Studies & Links in chronological order, with the latest on top:
Statins and risk of polyneuropathy, A case-control study
D. Gaist, MD, PhD; U. Jeppesen, MD, PhD; M. Andersen, MD, PhD; L.A. García
Rodríguez, MD, MSc;
J. Hallas, MD, PhD; and S.H. Sindrup, MD, PhD
http://213.4.18.135/87.pdf full text
Are users of lipid-lowering drugs at increased risk of peripheral neuropathy?
David Gaist, Luis Alberto García Rodríguez · Consuelo Huerta · Jesper Hallas · Søren H. Sindrup
http://213.4.18.135/75.pdf full text abstract
Are users of lipid-lowering drugs at increased risk of peripheral neuropathy?
David Gaist, Luis Alberto García Rodríguez · Consuelo Huerta · Jesper Hallas · Søren H.
http://213.4.18.135/76.2.pdf full text
http://213.4.18.135/87.pdf full text
Pharmacodynamics: Statins and peripheral neuropathy
U. Jeppesen (2), D. Gaist (1)(2), T. Smith (1), S. H. Sindrup (1)(2)
(1) Department of Neurology, Odense University Hospital, DK-5000 Odense C,
Denmark Tel.: +45-6541-2474, Fax: +45-6541-3389 (2) Department of Clinical Pharmacology Odense University, Odense, Denmark
Received: 6 July 1998 / Accepted in revised form: 1 October 1998
Abstract Volume 54 Issue 11 (1999) pp 835-838
http://link.springer-ny.com/link/service/journals/
00228/bibs/9054011/90540835.htm
Association of HMG-CoA reductase inhibitors with neuropathy.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=12549960&
dopt=Abstract
Ann Pharmacother. 2003 Feb;37(2):274-8.
Backes JM, Howard PA.
Department of Pharmacy Practice and Lipid, Atherosclerosis, Metabolic and
LDL-Apheresis Clinic, University of Kansas Medical Center, Kansas City, KS
"Epidemiologic studies and case reports suggest an increased risk of peripheral neuropathy with statin drugs. The majority of cases were at least partially reversible with drug cessation." (emphasis added)
Statin therapy and small fibre neuropathy: a serial electrophysiological study.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=12639733&
dopt=Abstract
Lo YL, Leoh TH, Loh LM, Tan CE.
J Neurol Sci. 2003 Apr 15;208(1-2):105-8.
Department of Neurology, Singapore General Hospital, Outram Road, Singapore.
Describes 3 patients who developed neuropathy after ONE MONTH of statin therapy. "One patient redeveloped small and large fibre neuropathy when the similar drug was readministered."
Peripheral Neuropathy and Lipid-Lowering Therapy
Paul E. Ziajka, MD, PhD, and Tammy Wehmeier, RN, Orlando, Fla.
Abstract: We report a case of peripheral neuropathy induced and excerbated by several commonly used HMG-CoA reductase inhibitors including lovastatin, simvastatin, pravastatin, and atorvastatin, and the vitamin niacin. A review of the literature shows similar cases with individual lipid-lowering drugs, but this case shows the cross-reactivity of the neuropathic process to different HMG-CoA reductase inhibitors, and is the first reported case of a peripheral neuropathy exacerbated by the use of niacin.
http://www.sma.org/smj1998/julysmj98/ziajka.pdf
"Increased levels of statin, a marker of cell cycle arrest, in response to hippocampal neuronal injury." Poirier J, Beffert U, Dea D, Alonso R,
O'Donnell D, Boksa P., Department of Psychiatry, McGill University,
Montreal, Que., Canada. Brain Res Mol Brain Res 1995 Dec 1;34(1):57-64
"It is concluded that, in addition to proliferation related gene products, neuronal injury induces an increase in levels of statin, a nuclear marker of cell cycle arrest. Furthermore, statin may be a potentially useful marker of injurious neuronal stress, even under conditions that do not necessarily lead to irreversible cell death."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=8750861&
dopt=Abstract
Phan T, McLeod JG, Pollard JD, Peiris O, Rohan A, Halpern JP.
Peripheral neuropathy associated with simvastatin.
J Neurol Neurosurg Psychiatry. 1995 May;58(5):625-8.
PMID: 7745415 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=7745415&
dopt=Abstract
Ahmad S.
Lovastatin and peripheral neuropathy.
Am Heart J. 1995 Dec;130(6):1321. No abstract available.
PMID: 7484806 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=7484806&
dopt=Abstract
Jacobs MB.
HMG-CoA reductase inhibitor therapy and peripheral neuropathy.
Ann Intern Med. 1994 Jun 1;120(11):970. No abstract available.
PMID: 8172444 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=8172444&
dopt=Abstract
Medication-induced peripheral neuropathy.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=12507417&
dopt=Abstract
Curr Neurol Neurosci Rep. 2003 Jan;3(1):86-92. Review.
Weimer LH.
Neurological Institute of New York, 710 West 168th Street, Unit 55, New
PMID: 12507417 [PubMed - indexed for MEDLINE]
"Although most cases demonstrate acute or subacute onset after exposure, recent experiences with statin drugs raise the possibility of occult toxic causes of chronic idiopathic neuropathy."
Le Quesne PM. Neuropathy due to drugs. In: Dyck PJ, Thomas PK, Griffin JW, et al, eds. Peripheral neuropathy. 3rd ed. Philadelphia: Saunders,
1993:1571-1581.
(Book, no link)
Of interest:
MacDonald BK, Cockerell OC, Sander WAS, Shorvon SD (2000) The incidence and lifetime prevalence of neurological disorders in a prospective community-based study in the UK. Brain
123:665-676
General background medical Info from
Related, but also will appear in other FAQs:
Neuromuscular Disease Center
Washington University School of Medicine, St. Louis, MO
Home:
http://www.neuro.wustl.edu/neuromuscular/index.html
Under Disorders & Syndromes:
Select:
Myopathy:
http://www.neuro.wustl.edu/neuromuscular/
maltbrain.html
Neuropathy:
http://www.neuro.wustl.edu/neuromuscular/
naltbrain.html
Neuromuscular:
http://www.neuro.wustl.edu/neuromuscular/
syaltbrain.html
CNS (Central Nervous System):
http://www.neuro.wustl.edu/neuromuscular/
syaltbrain.html#cns
MYOGLOBINURIA - RHABDOMYOLYSIS
http://www.neuro.wustl.edu/neuromuscular/msys/
myoglob.html
Then see Lipid Lowering Agent Myopathies
http://www.neuro.wustl.edu/neuromuscular/msys/
myoglob.html#lipid
Note that this connects to CARDIAC + MYOPATHY
http://www.neuro.wustl.edu/neuromuscular/msys/
cardiac.html
And to TOXIC NEUROPATHIES:
http://www.neuro.wustl.edu/neuromuscular/nother/
toxic.htm#statin
TOXIC MYOPATHIES
http://www.neuro.wustl.edu/neuromuscular/mother/
myotox.htm
Note also tht under Mitochondrial Disorders, the list of problems associated with Coenzyme Q10 Deficiency
http://www.neuro.wustl.edu/neuromuscular/msys/
myoglob.html#coq10
MITOCHONDRIAL MYOPATHIES
Facts About Mitochondrial Myopathies from the Muscular Dystrophy Association
http://www.mdausa.org/publications/
mitochondrial_myopathies.html#whatcauses
MEMORY LOSS & STATINS
Frequently Asked Question: What medical research studies have been done on
Statins and Memory Loss, or other mental problems that I can bring to my doctor's attention?
(Statins: Lipitor, Mevacor, Pravachol, Zocor, Lescol, and Baycol, aka atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, and simvastatin; Nerve Damage: Neuropathy, peripheral neuropathy, polyneuropathy; See separate FAQ for memory loss, cognitive damage, amnesia and aphasia, i.e., central nervous system (CNS) damage)
Australian Adverse Drug Reactions Bulletin (Australia's equivalent to the
FDA)
Volume 17, Number 3, August 1998, section 3, page 3
Simvastatn is listed under "DRUGS THAT MAKE YOU FORGET"
Recognizing the 14 reports of Amnesia under that drug, .8% of the total adverse effects for that drug.
www.health.gov.au/tga/docs/pdf/aadrbltn/aadr9808.pdf
Studies & Links in chronological order, with the latest on top:
Statin-associated memory loss: analysis of 60 case reports and review of the literature.
Wagstaff LR, Mitton MW, Arvik BM, Doraiswamy PM.
Drug Information Service, Duke University Medical Center, Durham, North
Carolina 27710, USA. Pharmacotherapy. 2003 Jul;23(7):871-80.
This study searched the MedWatch drug surveillance system of the Food and
Drug Administration (FDA) from November 1997-February 2002 for reports of statin-associated memory loss. They also reviewed the published literature.
References from the study are good for follow-up research.
Abstract:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=12885101&
dopt=Abstract
Full Study Text free on Medscape:
http://www.medscape.com/viewarticle/458867
The Role of Lipid-Lowering Drugs in Cognitive Function: A Meta-Analysis of
Observational Studies
from Pharmacotherapy
Posted 06/30/2003
Mahyar Etminan, Pharm.D., Sudeep Gill, M.D., FRCPC, Ali Samii, M.D., FRCPC
Although this study does bring the cognitive issues to light, it is a very poor study. The authors left out the pivotal study by Dr. Muldoon, that showed 100% of statin users had a measurable loss of cognitive ability after 6 months, while 100% of the placebo group improved their scores.
Abstract:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=12820814&
dopt=Abstract
Full Study Text free on Medscape:
http://www.medscape.com/viewarticle/456866
Muldoon MF, Barger SD, Ryan CM, Flory JD, Lehoczky JP, Matthews KA, Manuck
SB.
Effects of lovastatin on cognitive function and psychological well-being.
After 6 months, 100% of the patients on placeboes showed a measurable increase in cognitive function, and 100% of the statin patients showed a measurable decrease in cognitive function.
Am J Med. 2000 May;108(7):538-46.
PMID: 10806282 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=10806282&
dopt=Abstract
Simvastatin-Associated Memory Loss
Amanda Orsi, Pharm.D., Olga Sherman, Pharm.D., and Zegga Woldeselassie,
Pharm.D.,
Abstract: The statins are widely used to treat dyslipidemias. They are generally associated with mild adverse effects, but rarely, more serious reactions may occur. A 51-year-old man experienced delayed-onset, progressive memory loss while receiving simvastatin for hypercholesterolemia. His therapy was switched to pravastatin, and memory loss resolved gradually over the next month, with no recurrence of the adverse effect.
from Pharmacotherapy
Posted 06/01/2001
Page 1 of 3:
http://www.medscape.com/viewarticle/409738?
WebLogicSession=PXke2H8h99pyNVSCajAh5clptzOAHJSZuNBobSw
Wmi9veWjdJ2A3%7C-1468812056489609316/184161392/6/7001/
7001/7002/7002/7001/-1
full printable version:
http://www.medscape.com/viewarticle/409738_print
ADR of the Month
September 2001 Vol. 6 No. 9
Michelle W. McCarthy, Pharm.D.
Anne E. Hendrick, Pharm.D.
University of Virginia Health System
Department of Pharmacy Services
Drug Information Center
PO Box 800674
Charlottesville, VA 22908-0674
The Tablet, a general member benefit published by the British Columbia
Pharmacy Association, September 2001, Volume 10 no 8.
Excerpt:
Do HMG-CoA reductase inhibitors impair memory? After taking simvastatin for a year, a 51-year-old patient developed short term memory loss, to the extent of being unable to complete his sentences because he would forget what he was going to say. The drug was discontinued, replaced by pravastatin, and within one month his memory returned.14 In a separate case, a 67-year-old woman developed impaired short-term memory, altered mood, social impairment, cognitive impairment and dementia after one year of atorvastatin therapy. When atorvastatin was discontinued, her memory, mood and cognition improved completely.15 Memory impairment in a patient receiving atorvastatin has been reported to the BC Regional ADR Centre.
REFERENCES:
14. Orsi A, Sherman O, Woldeselassie Z. Simvastatin-associated memory loss.
15. King DS, Jones DW, Wofford MR et al. First report of cognitive impairment in an elderly patient: case report. Pharmacotherapy 2001 Mar; 21:
371.
http://www.bcpharmacy.ca/publications/thetablet/
pdf_version/BCPhA_Tablet-Sep2001.pdf
See page 11 of 16:
See also:
Statins and risk of polyneuropathy, A case-control study
D. Gaist, MD, PhD; U. Jeppesen, MD, PhD; M. Andersen, MD, PhD; L.A. García
Rodríguez, MD, MSc;
J. Hallas, MD, PhD; and S.H. Sindrup, MD, PhD
http://213.4.18.135/87.pdf full text
Preclinical safety evaluation of cerivastatin, a novel HMG-CoA reductase inhibitor.
von Keutz E, Schluter G.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=9737641&
dopt=Abstract
Institute of Toxicology, PH-Product Development, Bayer AG, Wuppertal,
Am J Cardiol. 1998 Aug 27;82(4
:11J-17J.
PMID: 9737641
"In dogs, the species most sensitive to statins, cerivastatin caused erosions and hemorrhages in the gastrointestinal tract, bleeding in the brain stem with fibroid degeneration of vessel walls in the choroid plexus, and lens opacity."
Subchronic toxicity of atorvastatin, a hydroxymethylglutaryl-coenzyme A reductase inhibitor, in beagle dogs.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=8864188&
dopt=Abstract
Walsh KM, Albassam MA, Clarke DE.
Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann
Arbor, Michigan 48105, USA.
"The toxicity of atorvastatin (AT), an inhibitor of hydroxymethylglutaryl-coenzyme A reductase (HMG), was evaluated in beagle dogs. hemorrhage in gallbladder and brain, demyelination of optic nerve, and skeletal muscle necrosis"
Finally, on memory loss and statins: Sworn testimony from the Baycol trial in Corpus Christi, Texas. From the transcript of the AM Session on 03-05-03, in the case Hollis Haltom Vs. Bayer Corporation. Testifying under oath,., in response to the plaintiff's attorney's question, "What is your current position at Bayer?", LAWRENCE POSNER, M.D of BAYER stated: "I'm the -- currently I'm the head of worldwide regulatory affairs for our prescription drug business, which means I have responsibility in somewhere between 60 and
100 countries where we sell products for registrations, compliance, things of that nature." Excerpts from the trial transcript follow, with the Q indicating counsel's Question, and the A indicating Dr. Posner's Answer:
Q. So there are some concerns addressed here back in 1995 about testing up to .8. And do you know what the nature of the concern was?
A. Yes. It was related to a side effect that occurred in the brain.
Q. Of what kind of animal?
A. It occurred in the brain of dogs.
Q. Okay. So there was a side effect that occurred in dogs, and then there was a concern about whether you wanted to go forward and test at this higher dose level in human beings, given what you had learned about the dogs, right?
A. That's correct.
Q. Okay. Now, did you just say, well, let's forget about these concerns and we'll go ahead and put .8 on the market anyway, or did you do some further analysis that was not mentioned the other day?
A. Yes. The authors of this had -- they had two concerns. One concern was the toxicity that they found in the brain of dogs. But the other was that they had no way to identify this and who might be at risk before it happened. So there was no way to detect that someone was at risk for this side effect.
[skip some testimony on other topics]
Q. Do you remember in one kind of animal there had been some studies done that there could be a particular kind of problem with one kind of animal?
A. Oh, yeah. Yes, from the -- that's correct, from the toxicology studies.
Q. Okay. And were you able to demonstrate to your own satisfaction, to
SmithKline's satisfaction, to the FDA's satisfaction, that that particular problem that showed up with that kind of animal is not something that happens in human beings?
A. Yes. We did it -- we did it by explaining the toxicology data. We also explained it on the basis of kinetic data. That actually at the higher levels of drug, what happens is a certain amount of drug is bound to proteins in the body that circulate; and therefore, is not -- cannot cause side effects. And actually, a much smaller proportion of the drug is free.
And that what you corrected for that, you actually found out that the margins of safety were in fact greater than you would predict just from the animal data.
Q. And as you move forward then and got approval and sold Baycol from 1997 through 2001, did that problem that had shown up with that one kind of animal ever become a problem with human beings?
A. It was actually shown with other statins as well. It wasn't unique to cerivastatin. It was a problem -- it was identified early on with lovastatin and some of the others. In fact, for none of the statins did it ever predict for any clinical problem or toxicity.
Q. So these animals would have that same problem regardless of which statin -- or at least with other statins?
A. Certainly with lovastatin it was true.
Q. But when it came time to human beings, that just wasn't something that happened to human beings?
A. And I think today no one pays much attention to it.
But, I thought I heard statins might cure Alzheimer's, what about that?
So far, there is no proof that statins have an effect on Alzheimers, while there is proof that statins negatively affect cognition and memory. Is it possible that the suggestion that statins may help Alzheimer's is just industry "spin" to divert attention from statin-induced memory loss?
Apparently so, because the adverse effects from the statins are cropping up so often that they are actually interfering with the ability of the industry to even run a study on statins and Alzheimers. See:
For all of us who experienced statin-caused cognitive effects, short-term memory loss, confusion, inability to concentrate, temporal global amnesia episodes, blackouts, etc. (in themselves or in a family member), this will come as absolutely no surprise:
http://now.humanapress.com/ArticleDetail.pasp?
issn=0895%2D8696&acode=JMN%3A20%3A3%3A407&
highlight=Sparks
A Position Paper: Based on Observational Data Indicating an Increased Rate of Altered Blood Chemistry Requiring Withdrawal from the Alzheimer's Disease
Cholesterol-Lowering Treatment Trial (ADCLT)
Authors are 6 clinical researchers from Sun City, AZ.
The doctors point out that the people taking the statins for the trial have to be pulled from the study due to adverse effects.
Unfortunately, this does not address the next issue they will encounter:
How will they be able to distinguish between Alzheimer's memory loss and statin-caused memory loss? Given that Dr. Muldoon's study proved that measurable cognitive deficits occur in 100% of the people taking statins, and given that fewer than 100% of the population suffers from Alzheimer's, it is inevitable they will have to deal with this issue - if they can keep enough people on the statins without adverse effects - something they are not experiencing success at now.
AMNESIA & STATINS
Frequently Asked Question: Amnesia is one of the Lipitor side effects reported by Pfizer on the Physician's Information, where can I find out more about people who have had amnesia episodes while taking the drug?
Dr. Graveline, retired family MD, USAF Flight Surgeon, researcher in space medicine and US Astronaut, who suffered adverse effects from Lipitor, maintains several websites and is working on a book about statin-related memory loss and amnesia at:
www.spacedoc.net (you can start here and read about his life and his books)
http://www.spacedoc.net/lipitor_thief_of_memory.html
http://www.spacedoc.net/lipitor.htm
http://www.spacedoc.net/statin_dialogues.htm
Australian Adverse Drug Reactions Bulletin (Australia's equivalent to the
FDA)
Volume 17, Number 3, August 1998, section 3, page 3
Simvastatn is listed under "DRUGS THAT MAKE YOU FORGET"
Recognizing the 14 reports of Amnesia under that drug, .8% of the total adverse effects for that drug.
www.health.gov.au/tga/docs/pdf/aadrbltn/aadr9808.pdf
CHEST PAIN & STATINS
Frequently Asked Question: Chest pain, that my cardiologist cannot explain via angiogram, stress test, EEG or EKG, is one of the side-effects I see is reported by many people. Is there any information on chest pain associated with statins?
Naturally, chest pain should be first evaluated by a cardiologist. If the usual explanations for chest pain do not apply to you, and you believe that statin adverse-effect may be the cause, here are some articles that may give you some background, or may be useful to give to your doctor. Some are specific to statins and cardiomyopathy, some are background on how statins affect CoQ10 production and how a CoQ10 deficiency affects the cells.
Most of these research articles have been found via a search of the National
Institutes of Health website
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=&
DB=PubMed , a repository for hundreds of medical journals. In most cases, only the abstract is available and the full article must be purchased. Many of the others can be found via a Google or other net search, or were discovered via posts on the
Lipitor message boards.
See:
http://www.lipitor.com/pi/default.asp Pfizer's Physician's Info for prescribing Lipitor, includes documented known adverse effects. Note "Body as a Whole: Chest pain," the italics indicate that the incidence was > 2% in original trials.
COENZYME Q10 (UBIQUINONE) DEFICIENCY CAUSED BY STATINS
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=12353945&
dopt=Abstract
Study report:
http://www.annals.org/issues/v137n7/nts/200210010-
00004.html
Dr. Phillips study mentioned in a Wall Street Journal article (This is smooth muscle, not cardiac muscle.) Conclusion "statin therapy may be associated with increased oxidation injury.mild adverse effects of statins that are difficult to assess might be much more prevalent than widely considered "
http://www.impostertrial.com Is Myopathy Part Of Statin Therapy? Dr.
Phillips study website, with info for Patient and Physician
Cohen & Gold, Mitochondrial Cytopathy in Adults: What we know so far
http://www.ccjm.org/pdffiles/COHEN701.PDF (See "Heart" in table page 4, and section on page 7) CoQ10 If statins cause
CoQ10 deficiency, and CoQ10 deficiency causes mitochondrial disease, what are the symptoms of mitochondrial disease? Heart pain is one of them.
Oxidation Injury in Patients Receiving HMG-CoA Reductase Inhibitors:
Occurrence in Patients without Enzyme Elevation or Myopathy.
US Patents: # 4,933,165
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&
amp;Sect2=HITOFF&d=PALL&p=1&u=/netahtml/
srchnum.htm&r=1&f=G&l=50&
s1=4933165.WKU.&OS=PN/4933165&RS=PN/4933165
see also subsequent related patents: Do a search by patent number at:
http://patft.uspto.gov/netahtml/srchnum.htm for the following:
United States Patent 5,082,650
United States Patent 5,849,777
United States Patent 6,264,960
Merck Patent application stating that statins interfere with CoQ10 and that deficiency causes problems. They documented that they knew this about statins in 1989, 10 years before the 100+ deaths by Rhabdomyolysis!
http://sites.huji.ac.il/malaria/maps/
ubiquinonemetpath.html
Malaria Parasite Metabolic Pathways Ubiquinone Metabolism another version:
http://www.stdgen.lanl.gov/stdgen/images/KEGG/
00130.html
DEFINITION Ubiquinone biosynthesis - Reference pathway. Diagram of the
Ubiquinone (aka CoQ10) metabolic pathway, highlighting exactly where the
Statins interrupt it. All of the 17 or so steps have to happen correctly for the body to produce CoQ10, but statins interrupt (or retard) this in step
#2.
Introduction to the Citizen's petition to the FDA:
Peter Langsjoen This is the introduction to the petition. (It is aimed at getting attention, and the wording may be more alarming than necessary.)
To the FDA: "Citizen Petition To Change The Labeling For All Statin Drugs (Mevacor, Lescol, Pravachol, Zocor, Lipitor, And Advicor) Recommending Use
Of 100-200mg Per Day Of Supplemental Co-Enzyme Ql0 To Reduce The Risk Of
Statin-Induced Myopathies (Including Cardiomyopathy And Congestive Heart
Failure)," by Dr. Julian Whitaker, MD:
http://www.fda.gov/ohrms/dockets/dailys/02/May02/
052902/02p-0244-cp00001-01-vol1.pdf or as html:
http://216.239.33.100/search?q=cache:4qAiX-YbZLYC:
www.fda.gov/ohrms/dockets/dailys/02/May02/052902/02p-
0244-cp00001-01-vol1.pdf+Statin-
Induced+Cardiomyopathy+Introduction+To+The+Citizen%
27s+Petition+On+Statins&hl=en&ie=UTF-8
Statin Depletion of CoQ10 is linked to heart problems.
Exhibit A of FDA Petition: "The clinical use of HMG CoA-reductase inhibitors (statins) and the associated depletion of the essential co-factor coenzyme
Ql0; a review of pertinent human and animal data." by Dr. Peter Langsjoen
MD:
http://www.fda.gov/ohrms/dockets/dailys/02/May02/
052902/02p-0244-cp00001-02-Exhibit_A-vol1.pdf
Examples of the heart problems associated with statin depletion of CoQ10.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=2247468&
dopt=Abstract
Lovastatin decreases coenzyme Q levels in humans.
Proc Natl Acad Sci U S A. 1990 Nov;87(22):8931-4.
PMID: 2247468 [PubMed - indexed for MEDLINE] A 1990 study showing depletion of CoQ10 by Lovastatin - includes descriptions of cardiac patients.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=11479481&
dopt=Abstract A
2001 discussion on "The effect of pravastatin and atorvastatin on coenzyme
Q10"
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/
C/CellularRespiration.html
Primer on how cells breathe normally (Note the role of CoQ10, called
"Ubiquinone" in "The Respiratory Chain" section.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=11505177&
dopt=Abstract (abstract)
http://213.4.18.135/70.pdf
http://216.239.33.100/search?q=cache:IGxCBJ3vs1kC:
213.4.18.135/70.pdf+gaist+statin+myopathy+risk+greater&
amp;hl=en&ie=UTF-8 view as html
Lipid-lowering drugs and risk of myopathy: a population-based follow-up study. Dr. Gaist is in Denmark and studies populations of entire countries for epidemiology information.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=12011277&
dopt=Abstract
Dr. Gaist's study, Statins and risk of polyneuropathy: a case-control study.
(more serious than peripheral neuropathy)
http://213.4.18.135/87.pdf Dr. Gaist's studies on Statin-induced nerve damage (full text)
Others:
Watts GF, Castelluccio C, Rice-Evans C, Taub NA, Baum H, Quinn PJ. Plasma coenzyme Q (ubiquinone) concentrations in patients treated with simvastatin.
J Clin Pathol. 1993;46:1055-7. [PMID: 8254097]
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?
db=m&form=6&Dopt=r&uid=PMID:
8254097
Mortensen SA, Leth A, Agner E, Rohde M. Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors. Mol Aspects
Med. 1997;18 Suppl
137-44. [PMID: 9266515]
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?
db=m&form=6&Dopt=r&uid=9266515
Bargossi AM, Grossi G, Fiorella PL, Gaddi A, Di Giulio R, Battino M.
Exogenous CoQ10 supplementation prevents plasma ubiquinone reduction induced by HMG-CoA reductase inhibitors. Mol Aspects Med. 1994;15 Suppl
187-93.
[PMID: 7752830]
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?
db=m&form=6&Dopt=r&uid=7752830
Ogasahara S, Engel AG, Frens D, Mack D. Muscle coenzyme Q deficiency in familial mitochondrial encephalomyopathy. Proc Natl Acad Sci U S A.
1989;86:2379-82. [PMID: 2928337]
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?
db=m&form=6&Dopt=r&uid=2928337
Baker SK, Tarnopolsky MA. Statin myopathies: pathophysiologic and clinical perspectives. Clin Invest Med. 2001;24:258-72. [PMID: 11603510]
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?
db=m&form=6&Dopt=r&uid=11603510
Rosenfeldt FL, Pepe S, Ou R, Mariani JA, Rowland MA, Nagley P, et al.
Coenzyme Q10 improves the tolerance of the senescent myocardium to aerobic and ischemic stress: studies in rats and in human atrial tissue. Biofactors.
1999;9:291-9. [PMID: 10416043]
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?
db=m&form=6&Dopt=r&uid=10416043
Reust CS, Curry SC, Guidry JR. Lovastatin use and muscle damage in healthy volunteers undergoing eccentric muscle exercise. West J Med.
1991;154:198-200. [PMID: 2006566]
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?
db=m&form=6&Dopt=r&uid=2006566
Statin-associated myopathy.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=12672737&
dopt=Abstract
Thompson PD, Clarkson P, Karas RH.
Preventive Cardiology and Cardiovascular Research, Division of Cardiology,
"recent evidence suggests that statins reduce the production of small regulatory proteins that are important for myocyte maintenance"
Statins and myotoxicity.
Curr Atheroscler Rep. 2003 Mar;5(2):96-100. Review.
PMID: 12573193 Farmer JA.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=12573193&
dopt=Abstract
Baylor College of Medicine, One Baylor Plaza, Room 525D, Houston, TX 77030,
CARNITINE DEFICIENCY CAUSED BY STATINS
Bhuiyan J, Seccombe DW. The effects of 3-hydroxy-3-methylglutaryl-CoA reductase inhibition on tissue levels of carnitine and carnitine acyltransferase activity in the rabbit. Lipids. 1996;31:867-70. [PMID:
8869889]
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?
db=m&form=6&Dopt=r&uid=8869889
JOINT PAIN AND STATINS
Frequently Asked Question: Can statins have something to do with my joint pain?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=11707010&
dopt=Abstract
Four cases of tendinopathy in patients on statin therapy.
Joint Bone Spine. 2001 Oct;68(5):430-3. PMID: 11707010 [PubMed - indexed for
MEDLINE]
Abstract on a report of 4 cases of people with painful tendons & statins.
Included to show that the pain and damage shows up in a variety of areas.
QUITTING STATINS
Frequently Asked Question: Can it be dangerous to just stop taking statins?
One study indicates that there are more coronary events when people stop taking statins (Definitely talk with your doctor on this):
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=11914253&
dopt=Abstract
Withdrawal of statins increases event rates in patients with acute coronary syndromes. The dangers of getting off statins. See also:
http://www.lipidsonline.org/commentaries/
al_abstract.cfm?abs_id=Abs030
VIOLENCE AND LOW CHOLESTEROL
Frequently Asked Questions: Can it be the statins making me so irritable and prone to angry outbursts?
It may be that the angry outbursts are caused by the Low Cholesterol, the result of taking Lipitor or other statins.
Dr. Beatrice Golomb, who is now conducting the NIH funded Statin Study, published 2 articles/studies on the connection between violence and low cholesterol levels.
See:
Low cholesterol and violent crime. Golomb BA, Stattin H, Mednick S.
Department of Medicine, University of California, Los Angeles, CA
92093-0995, USA. J Psychiatr Res 2000 Jul-Oct;34(4-5):301-9
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=11104842&
dopt=Abstract and
Cholesterol and violence: is there a connection? Golomb BA. Ann Intern Med
1998 Mar 15;128(6):478-87
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=9499332&
dopt=Abstract
IMMUNE SYSTEM AND STATINS
Frequently Asked Question: Can statins depress my immune system?
It is a tribute to the imaginations of the drug marketers to see how successfully they have put positive "spin" on a very alarming proposition, that statins depress the immune system (or is it just arrogance?). If the known side effect of statins is to depress your immune system, and it is so beneficial to transplant recipients and others with autoimmune disease, what about people with pre-statin 'normal' immune systems?
I'm not the only one astonished and disgusted with this, check out Dr.
Mercola's comment (scroll down for his response to the article) on
http://www.mercola.com/2000/dec/24/statins.htm
Excerpts: "This is an amazing example of positive "spin" put on a very negative result. People with high cholesterol certainly don't need their immune systems suppressed...If suppressing the helper T cells is considered such great benefit then there is a disease going around that does this quite well - AIDS...if the mechanism of action of the drug is not understood, how can the manufacturer or the FDA claim that it is safe"
It sounds like he is talking about this article
describing the last time the drug companies tried to feed us a myth about how great it is that statins depress immune systems: (available for online purchase from Nature Medicine:
http://www.nature.com/dynasearch/app/dynasearch.taf?sp-
w=Exact&_action=search&search_fulltext=&sp-
p=All&search_volume=&search_startpage=&
search_title=&s earch_author=&
search_abstract=statins+as+immunosuppressors&
issue_start_month =12&issue_start_year=2000&issue_end_month=01&
amp;issue_end_year=2001&pickerCount =You+have+selected+1+journal+to+search.&
rolloverMessage=&sp_k=NM
Atorvastatin suppresses interferon-gamma -induced neopterin formation and tryptophan degradation in human peripheral blood mononuclear cells and in monocytic cell lines.
Neurauter G, Wirleitner B, Laich A, Schennach H, Weiss G, Fuchs D.
Summary: Recent findings indicate that statins also have anti-inflammatory properties and can modulate the immune response.statins inhibit T cell activation within the cellular immune response.atorvastatin directly inhibits IFN-gamma-mediated pathways in monocytic cells, suggesting that both immunoreactivity of T cells and of monocyte-derived macrophages are down-regulated by this statin.
Clin Exp Immunol 2003 Feb;131(2):264-7
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=12562386&
dopt=Abstract
A novel anti-inflammatory role for simvastatin in inflammatory arthritis.
Leung BP, Sattar N, Crilly A, Prach M, McCarey DW, Payne H, Madhok R,
Campbell C, Gracie JA, Liew FY, McInnes IB.
J Immunol. 2003 Feb 1;170(3):1524-30.
PMID: 12538717 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=12538717&
dopt=Abstract
Immunomodulation: a new role for statins?
Wulf Palinski
SUMMARY: Statins reduce the expression of the class II major histocompatibility complex (MHCII) by arterial cells, leading to a decreased
T-cell response. This indicates that statins...
HMG-CoA reductase inhibitors as immunomodulators: potential use in transplant rejection.
Raggatt LJ, Partridge NC.
These findings suggest that statins have the potential to regulate an immune response in vivo and that more investigation is essential in order to explain the opposing clinical data.
Drugs. 2002;62(15):2185-91.
PMID: 12381218 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=12381218&
dopt=Abstract
Statins as a newly recognized type of immunomodulator
Brenda Kwak, Flore Mulhaupt, Samir Myit, François Mach
SUMMARY: Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
reductase, or statins, are effective lipid-lowering agents, extensively used in medical practice. Statins have never been shown to...
and could a depressed immune system lead to infection? See:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=11936540&
dopt=Abstract
Statin-induced fibrotic nonspecific interstitial pneumonia.
Eur Respir J. 2002 Mar;19(3):577-80.
PMID: 11936540 [PubMed - indexed for MEDLINE]
STATINS AND CANCER
Frequently Asked Question: What are the cancer rates for people on statins?
Despite the infomercial-type hype in recent press releases under titles like, "Does Lipitor prevent cancer?" (note it is a question, not an assertion), the numbers from recent studies tell the opposite story:
Statin use and the risk of breast cancer.
Beck P, Wysowski DK, Downey W, Butler-Jones D.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=12725884&
dopt=Abstract
J Clin Epidemiol. 2003 Mar;56(3):280-5.
PMID: 12725884 [PubMed - in process]
"Stratified analyses revealed increases in risk in short-term statin users and statin users with long-term hormone replacement therapy (HRT) exposure."
The PROSPER Study (PROspective study of pravastatin in the elderly at risk)
[Article in French]
Kulbertus H, Scheen AJ.
Service de Diabetologie, Nutrition et Maladies metaboliques et deMedecine
Interne Generale, CHU Liege.
Rev Med Liege. 2002 Dec;57(12):809-13.
"New cancers were more frequent amongst pravastatin-treated individuals (+25%; p = 0.020)."
Major Outcomes in Moderately Hypercholesterolemic, Hypertensive Patients Ran domized to Pravastatin vs Usual Care
The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack
Trial (ALLHAT-LLT)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=12479764&
dopt=Abstract
ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research
Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart
Attack Trial.
Deaths by cancer during the ALLHAT study: Pravastatin= 163; Usual Care= 148
6-year rate per 100 Participants: Pravastatin= 4.1; Usual Care= 3.7
ERECTILE DYSFUNCTION (ED) AND STATINS
Frequently Asked Question: Can statins interfere with my sex life?
Do lipid-lowering drugs cause erectile dysfunction? A systematic review.
Rizvi K, Hampson JP, Harvey JN.
University of Wales College of Medicine, Wrexham Academic Unit, Wrexham, UK.
Fam Pract. 2002 Feb;19(1):95-8. PMID: 11818357
BACKGROUND: Erectile dysfunction (ED) is common although under-reported by patients. Along with the better known causes of ED, drug-induced impotence needs to be considered as a cause of this symptom. Lipid-lowering drugs have been prescribed increasingly. Their relationship to ED is controversial.
OBJECTIVES: Our aim was to clarify the relationship between lipid-lowering therapy and ED. A secondary aim was to assess the value of the systematic review procedure in the area of adverse drug reactions. METHODS: A systematic review was carried out using computerized biomedical databases and Internet sources. Terms denoting ED were linked with terms referring to lipid-lowering drugs. Information was also sought from regulatory agencies.
RESULTS: A significant literature was identified, much from obscure sources, which included case reports, review articles, and information from clinical trials and from regulatory agencies. Information from all of these sources identified fibrates as a source of ED. A substantial number of cases of ED associated with statin usage have been reported to regulatory agencies. Case reports and clinical trial evidence supported the suggestion that statins can also cause ED. Some information on possible mechanisms was obtained, but the mechanism remains uncertain. CONCLUSIONS: The systematic review procedure was applied successfully to collect evidence suggesting that both statins and fibrates may cause ED. More numerous reports to regulatory agencies complemented more detailed information from case reports to provide a new perspective on a common area of prescribing.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=11818357&
dopt=Abstract
ERECTILE DYSFUNCTION AND STATIN THERAPY: INTERACTION WITH CARDIOVASCULAR
RISK FACTORS AND DRUG THERAPIES
H. Solomon1, J. Man1, Y.P. Samarasinghe2, M.D. Feher2, A.S. Wierzbicki3, G.
1Department of Cardiology, St. Thomas' Hospital, 2Beta Cell Diabetes Centre,
Chelsea & Westminster Hospital, 3Department of Chemical Pathology, St.
Thomas' Hospital, London UK
Erectile dysfunction has been associated with atherosclerotic risk factors and drugs used in their treatment. This study investigated the relationship of erectile function with cardiovascular risk factors and specific drug therapies. International Index of Erectile Function (IIEF) scores measured in 100 men attending cardiovascular risk clinics. Cardiovascular risk factors and drug therapies were assessed prior to initation and after 6 months of statin therapy. Before statin therapy no correlation was observed between IIEF score and any individual cardiovascular risk factor though better scores were observed in patients on warfarin or angiotensin-II receptor blocker therapy (r=0.42; p <0.001). After 6 months of statin therapy, significant correlations were observed between lower IIEF scores (r=0.62; P<0.001) and age, smoking, diabetes and usage of warfarin or angiotensin-2 type 1 receptor blocker (AR
therapy. Differences in dose, relative efficacy or relative lipophilicity of statin prescribed showed no correlation with change in IIEF score. This study suggests impotence following statin therapy is likelier in patients with more severe endothelial dysfunction due to established cardiovascular risk factors including age, and smoking and diabetes. This is complicated by adverse interactions between statin therapy and concomitant treatment with warfarin or angiotensin-II type I receptor blockers.
http://www.kenes.com/73eas/program/abstracts/126.doc
Drug Information Center: Information on Statin Drugs
"On March 7, 2002, Colorado HealthSite interviewed Beatrice A. Golomb, MD,
PhD, principal investigator of a study on Statin Drugs by the National
Institutes of Health. Dr. Golomb noted that the most common problems reported about statin drugs pertain to muscle pain or weakness, fatigue, memory and cognitive problems, sleep problems, and neuropathy. Erectile dysfunction, problems with temperature regulation (feeling hot or cold, or having sweats) are among the other problems reported. "
http://www.coloradohealthsite.org/pharmacology/
statins.html
"Question: What are the common complaints of patients who take statins?
Dr. Golomb: The most common problems we hear reported pertain to muscle pain or weakness, fatigue, memory and cognitive problems, sleep problems, and neuropathy. Erectile dysfunction, problems with temperature regulation (feeling hot or cold, or having sweats), are among the other problems reported. "
http://www.coloradohealthsite.org/topics/interviews/
golomb.html
Heart drug impotence warning
"Statins prevent heart attacks by reducing the levels of dangerous cholesterol in the bloodstream.
However, a small number of men prescribed the life-saving drug have complained that they are unable to achieve an erection."
"Dr John Harvey, from the Wrexham Maelor Hospital in Wales, identified 220 men who appeared to have lost their "virility" after starting to take statins. "
LUPUS-LIKE SYMPTOMS AND STATINS
Frequently Asked Question: Can statins cause Lupus symptoms?
Drug-induced lupus-like syndrome associated with severe autoimmune hepatitis.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=12765306&
dopt=Abstract
Graziadei IW, Obermoser GE, Sepp NT, Erhart KH, Vogel W.
Lupus. 2003;12(5):409-12.
PMID: 12765306 [PubMed - in process]
RHABDOMYOLYSIS AND STATINS
Frequently Asked Question: Which statins cause deadly Rhabdomyolysis?
All of them. See :
FDA adverse event reports on statin-associated rhabdomyolysis.
Omar MA, Wilson JP.
Ann Pharmacother. 2002 Feb;36(2):288-95. Review.
PMID: 11847951
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=11847951&
dopt=Abstract
Of 871 reports detailing 601 cases in a 29 month time frame, the list of statin, number of cases, and percentage of the whole follows:
simvastatin, 215 (35.8%);
cerivastatin, 192 (31.9%);
atorvastatin, 73 (12.2%);
pravastatin, 71 (11.8%);
lovastatin, 40 (6.7%);
fluvastatin, 10 (1.7%)
As of August, 2001, there were at least 81rhabdomyolysis deaths associated with Non-Baycol statins.
http://www.essentialdrugs.org/edrug/archive/200108/
msg00064.php
The Public Citizen petition to the FDA, August 20,2001:
http://www.citizen.org/publications/release.cfm?
ID=7051
At that time the count of deaths by statin-induced rhabdomyolysis:
Outcome Number of Cases Percent of Total Deaths
Deaths
Atorvastatin 13 18.1%
Cerivastatin 20 27.8%
Fluvastatin 1 1.4%
Lovastatin 5 6.9%
Pravastatin 9 12.5%
Simvastatin 24 33.3%
ELDERLY AND STATINS
Frequently Asked Question: Should people over 70 take statins?
Lack of association between cholesterol and coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years.
JAMA. 1994 Nov 2;272(17):1335-40.
Krumholz HM, Seeman TE, Merrill SS, Mendes de Leon CF, Vaccarino V,
Silverman DI, Tsukahara R, Ostfeld AM, Berkman LF.
Department of Internal Medicine, Yale University School of Medicine, New
Haven, CT 06520-8017.
"CONCLUSIONS--Our findings do not support the hypothesis that hypercholesterolemia or low HDL-C are important risk factors for all-cause mortality, coronary heart disease mortality, or hospitalization for myocardial infarction or unstable angina in this cohort of persons older than 70 years."
Another study showing people over 65 do not benefit from cholesterol reduction:
Long-Term Prognostic Importance of Total Cholesterol in Elderly Survivors of an Acute Myocardial Infarction: The Cooperative Cardiovascular Pilot
Project.
Foody JM, Wang Y, Kiefe CI, Ellerbeck EF, Gold J, Radford MJ, Krumholz HM.
Section of Cardiovascular Medicine, Department of Medicine, and Section of
Chronic Disease Epidemiology, Department of Epidemiology and Public Health,
Yale School of Medicine, New Haven, Connecticut; Qualidigm, Middletown,
Connecticut; Yale-New Haven Hospital Center for Outcomes Research and
Evaluation, New Haven, Connecticut; Center for Outcome and Effectiveness
Research and Education, University ofAlabama at Birmingham and Birmingham
Veterans Affairs Medical Center, Birmingham, Alabama; Department of
Preventive Medicine, University of Kansas School of Medicine, Kansas City,
Kansas; and Metastar, Madison, Wisconsin.
J Am Geriatr Soc. 2003 Jul;51(7):930-936. PMID: 12834512
"PARTICIPANTS: Four thousand nine hundred twenty-three Medicare beneficiaries from four states aged 65 and older"
"CONCLUSION: Among elderly survivors of AMI, elevated total serum cholesterol measured postinfarction is not associated with an increased risk of all-cause mortality in the 6 years after discharge. Furthermore, this study found no evidence of an increased risk of all-cause mortality in patients with low total cholesterol. Further studies are needed to determine the relationship of postinfarction lipid subfractions and mortality in older patients with coronary artery disease (CAD)."
High-density vs low-density lipoprotein cholesterol as the risk factor for coronary artery disease and stroke in old age.
Weverling-Rijnsburger AW, Jonkers IJ, van Exel E, Gussekloo J, Westendorp
RG.
Section of Gerontology and Geriatrics, Department of General Internal
Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Arch Intern Med. 2003 Jul 14;163(13):1549-54.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=PubMed&list_uids=12860577&
dopt=Abstract
"In contrast to high LDL cholesterol level, low HDL cholesterol level is a risk factor for mortality from coronary artery disease and stroke in old age."
Total cholesterol and risk of mortality in the oldest old.
Weverling-Rijnsburger AW, Blauw GJ, Lagaay AM, Knook DL, Meinders AE,
Westendorp RG.
Department of General Internal Medicine, Leiden University Medical Center,
The Netherlands.
Lancet. 1997 Oct 18;350(9085):1119-23.
" In people older than 85 years, high total cholesterol concentrations are associated with longevity owing to lower mortality from cancer and infection. The effects of cholesterol-lowering therapy have yet to be assessed."
Do Medical Journals agree that there is bias in drug-industry funded medical studies?
Yes, as does an observational study.
Association of Funding and Conclusions in Randomized Drug Trials
A Reflection of Treatment Effect or Adverse Events?
http://jama.ama-assn.org/cgi/content/abstract/290/7/
921
Bodil Als-Nielsen, MD; Wendong Chen, MD; Christian Gluud, MD, DMSc; Lise L.
Kjaergard, MD
JAMA. 2003;290:921-928 Vol 290 No 7, August 20, 2003
"The experimental drug was recommended as treatment of choice in 16% of trials funded by nonprofit organizations, 30% of trials not reporting funding, 35% of trials funded by both nonprofit and for-profit organizations, and 51% of trials funded by for-profit organizations (P<.001;
2 test). Logistic regression analyses indicated that funding, treatment effect, and double blinding were the only significant predictors of conclusions. Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice (odds ratio, 5.3; 95% confidence interval,
2.0-14.4) compared with trials funded by nonprofit organizations. This association did not appear to reflect treatment effect or adverse events. "
"Conclusions Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results. Readers should carefully evaluate whether conclusions in randomized trials are supported by data. "
"Author Affiliations: The Copenhagen Trial Unit, Center for Clinical
Intervention Research, Copenhagen University Hospital, Copenhagen, Denmark."
Clearly JAMA came to the conclusion that funding biases the findings in
2002, when they quite publicly changed their editorial policy to require funding information for studies they publish.
Further, you are invited to view the British Journal of Medicine, May 31,
2003 (Volume 326, Issue 7400), which has focused attention on bias and spin in industry-sponsored studies. They carried the following articles at
http://bmj.com/content/vol326/issue7400/#TWIB :
Research sponsored by drug companies is biased
http://bmj.com/content/vol326/issue7400/twib.shtml#326/
7400/0
No more free lunches
Kamran Abbasi and Richard Smith
BMJ 2003; 326: 1155-1156.
http://bmj.com/cgi/content/full/326/7400/1155 text
http://bmj.com/cgi/reprint/326/7400/1155 pdf
Drug company sponsorship of education could be replaced at a fraction of its cost
http://bm
