Updated 30 December 2004:

Frequently Asked Questions about Statin Adverse Effects

What are the names of the Statin drugs?

The Cholesterol-lowering Statin Drug Names: Lipitor, Crestor, Mevacor,
Pravachol, Zocor, Lescol, and Baycol, aka atorvastatin, rosuvastatin,
cerivastatin, fluvastatin, lovastatin, pravastatin, 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%20fro
m%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

What is the "Statin Study"?

Dr. Beatrice Golomb is doing research for the National Institutes of Health
(NIH) into "non-cardiac endpoints" of the statin drugs.  In other words,
what do statins do besides reducing serum cholesterol?  The UCSD Statin
Study is conducted at the University of California, San Diego, and it
accepts NO INDUSTRY FUNDING.  You can, and should, contact the Statin Study
with information on any adverse effects.  It is to everyone's benefit that
the UCSD Statin Study has the most complete set of information on statin
adverse effects in the world.  You can email, write, or call:

statinstudy@ucsd.edu

UCSD Statin Study
9500 Gilman Dr.
La Jolla, CA 92093-0995

(858) 558-4950

More information at the website: http://medicine.ucsd.edu/statin/index.htm

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/

The Canadian CBC News ran a series of consumer articles on March 25, 2003,
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. With rhabdomyolysis, death can result.  With other side
effects, disability can result.

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 some
cases, the doctor may simply be terrified of a malpractice charge.

That is one of the purposes for this FAQ - to give people an additional tool
to 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.

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

Also, there is a newsgroup (access via your email program):
sci.med.cardiology

Are there any books on the topic?

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 an excellent book about
statin-related memory loss and amnesia, "Lipitor, Thief of Memory",
available through Amazon.com and elsewhere, with more info available 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

As of mid-January, 2005, you can buy Dr. Graveline's second statin book,
"Statin Drugs - Side Effects and the Misguided War on Cholesterol."

See:

http://www.spacedoc.net/statin_side_effects.html

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 July 2004.

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  It includes the following:
anaphylaxis, angioneurotic edema, bullous rashes (including erythema
multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis), and
rhabdomyolysis.

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
UCSD STATIN STUDY E-MAIL ADDRESS: statinstudy@ucsd.edu
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/

OK, what should I take to my doctor?

The citations below are grouped by different categories of damage.  You can
take the entire list, but it may be better to select those areas that
describe the adverse effects you are concerned with.  You would do well,
however, to look at all of them, as people frequently have other concerns
they thought were unrelated until viewing the list of adverse effects.

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?

Chong PH, Boskovich A, Stevkovic N, Bartt RE.  Statin-associated peripheral
neuropathy: review of the literature.Pharmacotherapy. 2004
Sep;24(9):1194-203. Review. PMID: 15460180 [PubMed - indexed for
MEDLINE]http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra
ct&list_uids=15460180"Based
on epidemiologic studies as well as case reports, a risk of peripheral
neuropathy associated with statin use may exist; however, the risk appears
to be minimal. On the other hand, the benefits of statins are firmly
established. These findings should alert prescribers to a potential risk of
peripheral neuropathy in patients receiving any of the statins; that is,
statins should be considered the cause of peripheral neuropathy when other
etiologies have been excluded." Rajabally YA, Varakantam V, Abbott RJ.
Disorder resembling Guillain-Barre syndrome on initiation of statin
therapy.Muscle Nerve. 2004 Nov;30(5):663-6. PMID: 15389662 [PubMed - indexed
for
MEDLINE]http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra
ct&list_uids=15389662"We
report a disorder resembling Guillain-Barre syndrome, occurring on
initiation of simvastatin, in a 58-year-old man, who had experienced a
similar but milder episode after starting pravastatin 6 months earlier. This
case suggests that acute polyradiculoneuropathy may represent a rare but
serious side-effect of statin treatment. It also raises the issue of the
pathophysiology of acute neuropathy on statin exposure, with a
hypersensitivity reaction resulting in an immune-mediated process being
possible instead of the hypothesized mitochondrial dysfunction in chronic
cases." Scola RH, Trentin AP, Germiniani FM, Piovesan EJ, Werneck LC.
Simvastatin-induced mononeuropathy multiplex: case report.Arq
Neuropsiquiatr. 2004 Jun;62(2B):540-2. Epub 2004 Jul 20. PMID: 15273860
[PubMed - in
process]http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra
ct&list_uids=15273860"The
association between the use of statins and neuromuscular disease is
currently being intensely discussed. We relate a 63 years old man with
possible case of statin-induced neuropathy in a patient with dislipidemia in
use of simvastatina at high doses. The electrophysiologic studies disclosed
findings compatible with mononeuropathy multiplex, suggested by clinical
prescutation of asymmetrical numbness and weakness. More common causes of
mononeuropathy multiplex were excluded and the patient improved after the
discontinuation of the drug."
Statins and risk of polyneuropathy, A case-control study
D. Gaist, MD, PhD; U. Jeppesen, MD, PhD; M. Andersen, MD, PhD; L.A. Garc?a
Rodr?guez, MD, MSc;
J. Hallas, MD, PhD; and S.H. Sindrup, MD, PhD
http://213.4.18.135/87.pdf full text

From the abstract: "The authors verified a diagnosis of idiopathic
polyneuropathy in 166 cases. The cases were classified as definite (35),
probable (54), or possible (77). The odds ratio linking idiopathic
polyneuropathy with statin use was 3.7 (95% CI 1.8 to 7.6) for all cases and
14.2 (5.3 to 38.0) for definite cases. The corresponding odds ratios in
current users were 4.6 (2.1 to 10.0) for all cases and 16.1 (5.7 to 45.4)
for definite cases. For patients treated with statins for 2 or more years
the odds ratio of definite idiopathic polyneuropathy was 26.4 (7.8 to 45.4).
CONCLUSIONS: Long-term exposure to statins may substantially increase the
risk of polyneuropathy."

Are users of lipid-lowering drugs at increased risk of peripheral
neuropathy?
David Gaist, Luis Alberto Garc?a Rodr?guez ? Consuelo Huerta ? Jesper Hallas
? S?ren H. Sindrup
http://213.4.18.135/75.pdf full text
http://213.4.18.135/76.2.pdf full text
http://213.4.18.135/87.pdf full text 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=1
2549960&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
66160-7231, USA. jbackes@kumc.edu
"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)

Moosmann B, Behl C.  Selenoprotein synthesis and side-effects of
statins.Lancet. 2004 Mar 13;363(9412):892-4. Review. PMID: 15031036
[PubMed - indexed for
MEDLINE]http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra
ct&list_uids=15031036

"We noted that the pattern of side-effects associated with statins resembles
the pathology of selenium deficiency, and postulated that the mechanism lay
in a well established, but often overlooked, biochemical pathway--the
isopentenylation of selenocysteine-tRNA([Ser]Sec). A negative effect of
statins on selenoprotein synthesis does seem to explain many of the
enigmatic effects and side-effects of statins, in particular, statin-induced
myopathy."

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=1
2639733&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.
gnrlyl@sgh.com.sg
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

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=7
745415&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=7
484806&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=8
172444&dopt=Abstract

Medication-induced peripheral neuropathy.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1
2507417&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
York, NY 10032, USA. Lhw1@columbia.edu
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

Specifics,
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
OR Locally supplied Search on "Statin" leads to:
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=1
2885101&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=1
2820814&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=1
0806282&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=PXke2H8h99pyNVSCajAh5
clptzOAHJSZuNBobSwWmi9veWjdJ2A3%7C-1468812056489609316/184161392/6/7001/7001/700
2/7002/7001/-1

full printable version: http://www.medscape.com/viewarticle/409738_print

ADR of the Month
September 2001 Vol. 6 No. 9
EDITORS
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
http://hsc.virginia.edu/pharmacy-services/Newsletters/ADR%20of%20the%20Month/ADR
Month%209-01htm.html

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. Garc?a
Rodr?guez, 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=9
737641&dopt=Abstract
Institute of Toxicology, PH-Product Development, Bayer AG, Wuppertal,
Germany
Am J Cardiol. 1998 Aug 27;82(4B):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=8
864188&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.

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.

Phillips PS, Phillips CT, Sullivan MJ, Naviaux RK, Haas RH.

Statin myotoxicity is associated with changes in the cardiopulmonary
function.

Atherosclerosis. 2004 Nov;177(1):183-8.

PMID: 15488882 [PubMed - in process]

Scripps Mercy Clinical Research Center, Scripps Mercy Hospital, Cardiology
(Mer 74), Catheterization Laboratories, Scripps Mercy Hospital, 4077 Fifth
Avenue, San Diego, CA 92103, USA. phillips.paul@scrippshealth.org

"The mechanism of the muscle toxicity associated with lipid-lowering therapy
remains obscure. Pathological and biochemical findings in patients with
statin myotoxicity suggest impaired fatty acid oxidation. Exhaled gas
analysis can be used to assess substrate utilization including fatty acid
oxidation. In order to determine if muscle toxicity due to lipid-lowering
therapy might be related to abnormalities in lipid oxidation, exhaled gas
analysis was performed in the fasted state on 11 patients subsequent to
statin-associated myositis reactions. Results were compared to those of 16
normal controls who were measured both on and off statin therapy.
Post-myositis patients showed a depressed anaerobic threshold (AT) (P=0.009)
compared to controls while age-adjusted maximal oxygen consumption (VO2max)
and ventilatory efficiency (VE/VCO2) were not significantly different. The
fasting respiratory exchange ratio (RER) of post-myositis patients off
statins was abnormally increased (P=0.00001) as was their S1-slope
(P=0.023). Controls demonstrated a significant increase in their RER while
taking statins consistent with decreased lipid oxidation (P <0.00001). These
findings suggest that abnormal lipid oxidation in certain patients may
predispose them to the myotoxicity caused by lipid-lowering therapies."

1:  Silver MA, Langsjoen PH, Szabo S, Patil H, Zelinger A.  Effect of
atorvastatin on left ventricular diastolic function and ability of coenzyme
Q10 to reverse that dysfunction.Am J Cardiol. 2004 Nov 15;94(10):1306-10.
PMID: 15541254 [PubMed - indexed for MEDLINE]"This study evaluated left
ventricular diastolic function with Doppler echocardiography before and
after statin therapy. Statin therapy worsened diastolic parameters in most
patients; coenzyme Q(10) supplementation in patients with worsening
diastolic function with statin therapy improved parameters of diastolic
function." 2:  Silver MA, Langsjoen PH, Szabo S, Patil H, Zelinger A.
Statin cardiomyopathy? A potential role for Co-Enzyme Q10 therapy
forstatin-induced changes in diastolic LV performance: description of a
clinical protocol.Biofactors. 2003;18(1-4):125-7. PMID: 14695927 [PubMed -
indexed for MEDLINE]"Lipid-lowering statins are thought to have a favorable
safety profile. Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A
(HMG-CoA) reductase, the rate-limiting step of mevalonate synthesis.
Mevalonate is the substrate for further synthesis of cholesterol and Co
Enzyme Q10 (CoQ10). CoQ10 plays an important role during oxidative
phosphorylation in the myocardial cell. Since myocardial diastolic function
is a highly ATP dependent, we reasoned that early changes of diastolic
function may be an early marker of ventricular dysfunction. METHODS:
Patients who are to commence on statin therapy will be enrolled in the
trial. Baseline measurements of plasma CoQ10, total cholesterol, LDL, HDL,
CoQ10/LDL ratio, peak E, peak A velocities, E/A ratio, deceleration time,
isovolumetric relaxation time, color M-mode propagation velocity will be
performed and patients will then begin to take Oral atorvastatin (Lipitor,
Parke-Davis) 20 mg daily for three to six months. All baseline measurement
will be repeated after 3 to 6 months of statin therapy. Those patients
demonstrating > 1 measurement of diastolic LV function that worsened during
the 3 to 6 months of statin therapy will be supplemented with CoQ10 300 mg.
daily for 3 months. A followup echocardiogram and blood CoQ10 level will be
measured in patients who received CoQ10 supplementation. RESULTS:
Statistical analysis will be performed using the paired t test to compare
coenzyme levels and echocardiographic indices at baseline and after
treatment and after supplementation."  3:  Langsjoen PH, Langsjoen AM.  The
clinical use of HMG CoA-reductase inhibitors and the associated depletion of
coenzyme Q10. A review of animal and human publications.Biofactors.
2003;18(1-4):101-11. Review. PMID: 14695925 [PubMed - indexed for
MEDLINE]"The
depletion of the essential nutrient CoQ10 by the increasingly popular
cholesterol lowering drugs, HMG CoA reductase inhibitors (statins), has
grown from a level of concern to one of alarm. With ever higher statin
potencies and dosages, and with a steadily shrinking target LDL cholesterol,
the prevalence and severity of CoQ10 deficiency is increasing noticeably. An
estimated 36 million Americans are now candidates for statin drug therapy.
Statin-induced CoQ10 depletion is well documented in animal and human
studies with detrimental cardiac consequences in both animal models and
human trials. This drug-induced nutrient deficiency is dose related and more
notable in settings of pre-existing CoQ10 deficiency such as in the elderly
and in heart failure. Statin-induced CoQ10 deficiency is completely
preventable with supplemental CoQ10 with no adverse impact on the
cholesterol lowering or anti-inflammatory properties of the statin drugs. We
are currently in the midst of a congestive heart failure epidemic in the
United States, the cause or causes of which are unclear. As physicians, it
is our duty to be absolutely certain that we are not inadvertently doing
harm to our patients by creating a wide-spread deficiency of a nutrient
critically important for normal heart function."

COENZYME Q10 (UBIQUINONE) DEFICIENCY CAUSED BY STATINS

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1
2353945&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&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:
http://www.vaccinationnews.com/DailyNews/July2002/StatinInduced8.htm by Dr.
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/dail
ys/02/May02/052902/02p-0244-cp00001-01-vol1.pdf+Statin-Induced+Cardiomyopathy+In
troduction+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-Exhi
bit_A-vol1.pdf

Effect of atorvastatin on left ventricular diastolic function and ability of
coenzyme Q10 to reverse that dysfunction.
Silver MA, Langsjoen PH, Szabo S, Patil H, Zelinger A.
Am J Cardiol. 2004 Nov 15;94(10):1306-10.
Heart Failure Institute, Department of Medicine, Advocate Christ Medical
Center, University of Illinois/Christ Cardiovascular Disease Fellowship
Program, Oak Lawn, Illinois 60453, USA. marc.silver@advocatehealth.com
<marc.silver@advocatehealth.com>
"This study evaluated left ventricular diastolic function with Doppler
echocardiography before and after statin therapy. Statin therapy worsened
diastolic parameters in most patients; coenzyme Q(10) supplementation in
patients with worsening diastolic function with statin therapy improved
parameters of diastolic function."

Examples of the heart and other problems associated with statin depletion of
CoQ10.

1:  Silver MA, Langsjoen PH, Szabo S, Patil H, Zelinger A.  Effect of
atorvastatin on left ventricular diastolic function and ability ofcoenzyme
Q10 to reverse that dysfunction.Am J Cardiol. 2004 Nov 15;94(10):1306-10.
PMID: 15541254 [PubMed - indexed for MEDLINE] 2:  Rundek T, Naini A, Sacco
R, Coates K, DiMauro S.  Atorvastatin decreases the coenzyme Q10 level in
the blood of patients at riskfor cardiovascular disease and stroke.Arch
Neurol. 2004 Jun;61(6):889-92. PMID: 15210526 [PubMed - indexed for MEDLINE]
3:  Ornato JP.  Questions & answers. I take a statin to lower my LDL (bad)
cholesterol level,but I've heard statins inhibit the production of coenzyme
Q10 (CoQ10). Should Itake a CoQ10 supplement?Health News. 2004 Apr;10(4):16.
No abstract available. PMID: 15088591 [PubMed - indexed for MEDLINE] 4:
Silver MA, Langsjoen PH, Szabo S, Patil H, Zelinger A.  Statin
cardiomyopathy? A potential role for Co-Enzyme Q10 therapy forstatin-induced
changes in diastolic LV performance: description of a
clinicalprotocol.Biofactors. 2003;18(1-4):125-7. PMID: 14695927 [PubMed -
indexed for MEDLINE] 5:  Passi S, Stancato A, Aleo E, Dmitrieva A, Littarru
GP.  Statins lower plasma and lymphocyte ubiquinol/ubiquinone without
affectingother antioxidants and PUFA.Biofactors. 2003;18(1-4):113-24. PMID:
14695926 [PubMed - indexed for MEDLINE] 6:  Langsjoen PH, Langsjoen AM.  The
clinical use of HMG CoA-reductase inhibitors and the associated depletionof
coenzyme Q10. A review of animal and human publications.Biofactors.
2003;18(1-4):101-11. Review. PMID: 14695925 [PubMed - indexed for MEDLINE]
7:  Pettit FH, Harper RF, Vilaythong J, Chu T, Shive W.  Reversal of statin
toxicity to human lymphocytes in tissue culture.Drug Metabol Drug Interact.
2003;19(3):151-60. PMID: 14682607 [PubMed - indexed for MEDLINE] 8:  Wolters
M, Hahn A.  Plasma ubiquinone status and response to six-month
supplementation combinedwith multivitamins in healthy elderly women--results
of a randomized,double-blind, placebo-controlled study.Int J Vitam Nutr Res.
2003 May;73(3):207-14. PMID: 12847998 [PubMed - indexed for MEDLINE] 9:
Hargreaves IP.  Ubiquinone: cholesterol's reclusive cousin.Ann Clin Biochem.
2003 May;40(Pt 3):207-18. Review. PMID: 12803831 [PubMed - indexed for
MEDLINE] 10:  [No authors listed]  Extra co-enzyme Q10 for
statin-users?Treatmentupdate. 2001 Jun;13(2):4-7. PMID: 11570288 [PubMed -
indexed for MEDLINE] 11:  Fosslien E.  Mitochondrial medicine--molecular
pathology of defective oxidativephosphorylation.Ann Clin Lab Sci. 2001
Jan;31(1):25-67. Review. PMID: 11314862 [PubMed - indexed for MEDLINE] 12:
Kaikkonen J, Nyyssonen K, Tomasi A, Iannone A, Tuomainen
TP,Porkkala-Sarataho E, Salonen JT.  Antioxidative efficacy of parallel and
combined supplementation with coenzyme Q10 and d-alpha-tocopherol in mildly
hypercholesterolemic subjects: a randomizedplacebo-controlled clinical
study.Free Radic Res. 2000 Sep;33(3):329-40. PMID: 10993487 [PubMed -
indexed for MEDLINE] 13:  Levin WM.  Statin drugs: a double-edged sword?Hosp
Pract (Off Ed). 1997 Aug 15;32(8):44. No abstract available. PMID: 9275961
[PubMed - indexed for MEDLINE] 14:  De Pinieux G, Chariot P, Ammi-Said M,
Louarn F, Lejonc JL, Astier A,Jacotot B, Gherardi R.  Lipid-lowering drugs
and mitochondrial function: effects of HMG-CoA reductase inhibitors on serum
ubiquinone and blood lactate/pyruvate ratio.Br J Clin Pharmacol. 1996
Sep;42(3):333-7. PMID: 8877024 [PubMed - indexed for MEDLINE] 15:  Fjelstrup
A.  [Statin therapy and heart failure. There is a difference between
statins]Tidsskr Nor Laegeforen. 1994 May 20;114(13):1561-2.  Norwegian. No
abstractavailable. PMID: 8079255 [PubMed - indexed for MEDLINE] 16:  Carlsen
SM, Fougner KJ.  [Statin therapy, Q10 and heart failure. Is there any
difference between statins?]Tidsskr Nor Laegeforen. 1994 Apr
30;114(11):1345.  Norwegian. No abstractavailable. PMID: 8079217 [PubMed -
indexed for MEDLINE] 17:  Hyams DE, Roylance PJ, Kruger K, Bodd E.  [Do we
kill our cardiac patients with statin therapy? Coenzyme Q10, what do we
know?]Tidsskr Nor Laegeforen. 1994 Feb 20;114(5):590.  Norwegian. No
abstractavailable. PMID: 7748252 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2
247468&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=1
1479481&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=1
1505177&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+stat
in+myopathy+risk+greater&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=1
2011277&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&colon;
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:S137-44. [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:s187-93.
[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=1
2672737&dopt=Abstract
Thompson PD, Clarkson P, Karas RH.
Preventive Cardiology and Cardiovascular Research, Division of Cardiology,
Hartford Hospital, Hartford, Conn 06102, USA. pthomps@harthosp.org
"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=1
2573193&dopt=Abstract
Baylor College of Medicine, One Baylor Plaza, Room 525D, Houston, TX 77030,
USA. jfarmer@bcm.tmc.edu

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=1
1707010&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=1
1914253&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

STATIN BIRTH DEFECTS

Frequently Asked Question: Is statin intake during pregnancy dangerous for
unborn children?

Edison RJ, Muenke M.

Central nervous system and limb anomalies in case reports of
first-trimester statin exposure.

N Engl J Med. 2004 Apr 8;350(15):1579-82. No abstract available.

PMID: 15071140 [PubMed - indexed for MEDLINE]

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=1
1104842&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=9
499332&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
http://pub.ucsf.edu/today/print.php?news_id=200211062 , but actually he is
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&se
arch_fulltext=&sp-p=All&search_volume=&search_startpage=&search_title=&search_au
thor=&search_abstract=statins+as+immunosuppressors&issue_start_month=12&issue_st
art_year=2000&issue_end_month=01&issue_end_year=2001&pickerCount=You+have+select
ed+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=1
2562386&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=1
2538717&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...
Nature Medicine6, 1311 - 1312 (01 Dec 2000) News and Views

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=1
2381218&dopt=Abstract

Statins as a newly recognized type of immunomodulator
Brenda Kwak, Flore Mulhaupt, Samir Myit, Fran?ois 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...
Nature Medicine 6, 1399 - 1402 (01 Dec 2000) Article

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=1
1936540&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=1
2725884&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
Randomized 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=1
2479764&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=1
1818357&dopt=AbstractERECTILE DYSFUNCTION AND STATIN THERAPY:INTERACTION WITH CARDIOVASCULARRISK FACTORS AND DRUG THERAPIESH. Solomon1,J. Man1, Y.P. Samarasinghe2, M.D. Feher2, A.S. Wierzbicki3,G.Jackson11Department of Cardiology, St. Thomas' Hospital, 2Beta CellDiabetes Centre,Chelsea & Westminster Hospital, 3Department of ChemicalPathology, St.Thomas' Hospital, London UKErectile dysfunction has beenassociated with atherosclerotic risk factorsand drugs used in theirtreatment. This study investigated the relationshipof erectile function withcardiovascular risk factors and specific drugtherapies. International Indexof Erectile Function (IIEF) scores measuredin 100 men attendingcardiovascular risk clinics. Cardiovascular riskfactors and drug therapieswere assessed prior to initation and after 6months of statin therapy. Beforestatin therapy no correlation was observedbetween IIEF score and anyindividual cardiovascular risk factor thoughbetter scores were observed inpatients on warfarin or angiotensin-IIreceptor blocker therapy (r=0.42; p<0.001). After 6 months of statintherapy, significant correlations wereobserved between lower IIEF scores(r=0.62; P<0.001) and age, smoking,diabetes and usage of warfarin orangiotensin-2 type 1 receptor blocker (ARB)therapy. Differences in dose,relative efficacy or relative lipophilicity ofstatin prescribed showed nocorrelation with change in IIEF score. This studysuggests impotencefollowing statin therapy is likelier in patients with moresevereendothelial dysfunction due to established cardiovascular riskfactorsincluding age, and smoking and diabetes. This is complicated byadverseinteractions between statin therapy and concomitant treatment withwarfarinor angiotensin-II type I receptorblockers.http://www.kenes.com/73eas/program/abstracts/126.docDrug Information Center: Information on Statin Drugs"On March 7, 2002,Colorado HealthSite interviewed Beatrice A. Golomb, MD,PhD, principalinvestigator of a study on Statin Drugs by the NationalInstitutes of Health.Dr. Golomb noted that the most common problemsreported about statin drugspertain to muscle pain or weakness, fatigue,memory and cognitive problems,sleep problems, and neuropathy. Erectiledysfunction, problems withtemperature regulation (feeling hot or cold, orhaving sweats) are among theother problems reported."http://www.coloradohealthsite.org/pharmacology/statins.html"Question: Whatare the common complaints of patients who take statins?Dr. Golomb: The mostcommon problems we hear reported pertain to muscle painor weakness, fatigue,memory and cognitive problems, sleep problems, andneuropathy. Erectiledysfunction, problems with temperature regulation(feeling hot or cold, orhaving sweats), are among the other problemsreported. "http://www.coloradohealthsite.org/topics/interviews/golomb.htmlBBC News:Wednesday, 15 March, 2000, 19:02 GMTHeart drug impotence warning"Statins prevent heart attacks by reducing the levels ofdangerouscholesterol in the bloodstream. However, a small number of menprescribed the life-saving drug havecomplained that they are unable toachieve an erection.""Dr John Harvey, from the Wrexham Maelor Hospital inWales, identified 220men who appeared to have lost their "virility" afterstarting to takestatins. "http://news.bbc.co.uk/1/hi/health/678811.stmBaileyDG, Dresser GK.  Interactions between grapefruit juice andcardiovasculardrugs.Am J Cardiovasc Drugs. 2004;4(5):281-97. Review. PMID:15449971[PubMed - indexed for MEDLINE] Blumentals WA, Brown RR,Gomez-Caminero A.Antihypertensive treatment and erectile dysfunction in acohort of typeIIdiabetes patients.Int J Impot Res. 2003 Oct;15(5):314-7.PMID: 14562130[PubMed - indexed for MEDLINE]LUPUS-LIKE SYMPTOMS AND STATINSFrequently Asked Question: Can statins cause Lupus symptoms?Drug-inducedlupus-like syndrome associated with severeautoimmunehepatitis.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1
2765306&dopt=AbstractGraziadei IW, Obermoser GE,Sepp NT, Erhart KH, Vogel W.Lupus. 2003;12(5):409-12.PMID: 12765306[PubMed - in process]"Atorvastatin and other members of the statin familyare widely used for thetreatment of hypercholesterolaemia in order to reducethe risk ofatherosclerosis and cardiovascular disease. Atorvastatin-inducedadverseevents are mostly mild and only a few cases of lupus-like syndrome orsevereacute hepatitis have been documented. In this case report we describeapatient who developed an atorvastatin-induced severe autoimmunehepatitis.In addition, this patient presented with a concomitant systemiclupus-likesyndrome which has been already described for statins but not inassociationwith severe liver disease. Although the drug was immediatelywithdrawn thedisease persisted and even deteriorated to a fulminant diseasewith evidenceof acute hepatic failure. The patient failed to respond toconventionalimmunosuppression with corticosteroids and azathioprine. Onlytheintroduction of intense immunosuppressive therapy, as used in solidorgantransplantation, led to a complete and sustained recovery of thepatient.Interestingly, the patient was HLA DR3- and HLA DR4-positive, whicharewell-known genetic factors associated with autoimmune diseases. This caseisthe first report of a drug-induced lupus-likesyndrome concomitant withasevere autoimmune hepatitis in a genetically predisposed patient."Noel B,Panizzon RG.  Lupus-like syndrome associated with statintherapy.Dermatology.2004;208(3):276-7. PMID: 15118389 [PubMed - indexed forMEDLINE]"Statins are among the most widely prescribed drugs. An increasingnumber oflupus-like syndrome has recently been reported with theselipid-loweringagents. We describe a new case associated with simvastatintherapy. Thepresence of anti-dsDNA antibodies in the serum is for the firsttime reportedconfirming that statins may also induce a systemic autoimmunereaction.Statin-induced lupus-like syndrome is characterized by the longdelay betweenthe beginning of therapy and the skin eruption. Antinuclearantibodies maypersist for many months after drug discontinuation. Thecausal relationshipmay be therefore difficult to establish, and probablymany cases areunrecognized. Early diagnosis may avoid unnecessaryimmunosuppressivetherapy. Copyright 2004 S. Karger AG, Basel" Lantuejoul S,Brambilla E,Brambilla C, Devouassoux G.  Statin-induced fibroticnonspecific interstitialpneumonia.Eur Respir J. 2002 Mar;19(3):577-80.PMID: 11936540 [PubMed -indexed for MEDLINE]"Statins inhibit the3-hydroxy-3-methylglutaryl coenzyme A reductase, reducethe serum level oflow-density lipoprotein cholesterol, and are extensivelyprescribed toprevent cardiovascular mortality and morbidity. Few systemicadverseeffects, such as pseudopolymyositis, lupus-like syndromes, andanecdotalhypersensitivity pneumonitis, have been reported. Asimvastatin-induceddiffuse interstitial pneumonia associated with anonspecific interstitialpneumonia pattern at histological analysis isrepoted here. Ultrastructuralanalysis showed a diffuse cytoplasmicaccumulation of intralysosomiallamellar inclusions in type II pneumonocytes,histiocytes and endothelialcells, suggesting a shared pathogenesis withamphiphilic drug-induced toxiclung injury. Because statins are increasinglyprescribed, statin-inducedinterstitial lung disorders may be more frequentlyobserved and earlyrecognition will be required." Chazerain P, Hayem G, HamzaS, Best C, ZizaJM.  Four cases of tendinopathy in patients on statintherapy.Joint BoneSpine. 2001 Oct;68(5):430-3. PMID: 11707010 [PubMed -indexed for MEDLINE]"During the last decade, statins have been widely prescribed aslipid-loweringdrugs. Their overall safety profile is good. The mainmusculoskeletal sideeffects have consisted of muscle pain and weakness,peripheral neuropathy,and a few cases of drug-induced lupus. We report thefirst four cases oftendinopathy in patients receiving statin therapy. Therewere three men andone woman. The diagnoses were extensortenosynovitis atthe hands (case 1),tenosynovitis of the tibialis anterior tendon (case 2),and Achillestendinopathy (cases 3 and 4). Two patients were on simvastatinand two onatorvastatin. The tendinopathy developed 1 to 2 months aftertreatmentinitiation. The outcome was consistently favorable within 1 to 2months afterdiscontinuation of the drug. Similar cases have been reportedto Frenchpharmacovigilance centers. This report of four cases oftendinopathy drawsattention to a possible and heretofore unrecognized sideeffect of a drugclass that is becoming increasingly popular. Statins areeffective inlowering high cholesterol levels in patients with type IIa orIIbhypercholesterolemia. They have been widely used for the lastdecade,particularly in the secondary and primary prevention of majorcoronaryevents. Statins act by inhibiting theenzymehydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase. Althoughmostpatients tolerate statins extremely well, a few experience sideeffectsrequiring treatment discontinuation. Reported musculoskeletal sideeffectsinclude myalgia and a few cases of rhabdomyolysis and polymyositis.Inducedlupus and peripheral neuropathy are exceedingly rare."MYOPATHY AND STATINSFrequently Asked Question: Do statins cause muscle damage, musclepain,myopathy, myositis, and muscle cell death (apoptosis) with orwithoutelevated CK?1:  Phillips PS.  Ezetimibe and statin-associated myopathy.Ann InternMed.2004 Oct 19;141(8):649. No abstract available. PMID: 15492351[PubMed -indexed for MEDLINE]2:  Phillips PS, Phillips CT, Sullivan MJ, Naviaux RK,Haas RH.  Statinmyotoxicity is associated with changes in thecardiopulmonaryfunction.Atherosclerosis. 2004 Nov;177(1):183-8. PMID:15488882 [PubMed - inprocess]3:  Phillips PS, Haas RH, Bannykh S, HathawayS, Gray NL, Kimura BJ,VladutiuGD, England JD; Scripps Mercy ClinicalResearch Center.Statin-associated myopathy with normal creatine kinaselevels.Ann Intern Med.2002 Oct 1;137(7):581-5. PMID: 12353945 [PubMed -indexed for MEDLINE]And more:Search terms "STATIN + MYOPATHY":1:  Koller H, Neuhaus O, Schroeter M, Hartung HP.  [Myopathies undertherapywith lipid-lowering agents.]Nervenarzt. 2004 Dec 18; [Epub ahead ofprint]German. PMID: 15609055 [PubMed - as supplied by publisher]2:  [No authorslisted]  A warning about one statin at a high dose.HeartAdvis. 2004Nov;7(11):2. No abstract available. PMID: 15580669 [PubMed -indexed forMEDLINE]3:  Graham DJ, Staffa JA, Shatin D, Andrade SE, Schech SD, LaGrenade L,GurwitzJH, Chan KA, Goodman MJ, Platt R.  Incidence ofhospitalizedrhabdomyolysis in patients treated withlipid-loweringdrugs.JAMA. 2004 Dec1;292(21):2585-90. Epub 2004 Dec 1. PMID: 15572716[PubMed - indexed forMEDLINE]4:  [No authors listed]  Safety of aggressivestatin therapy.Med Lett DrugsTher. 2004 Nov 22;46(1196):93-5. PMID:15557874 [PubMed - indexed forMEDLINE]5:  Anfossi G, Massucco P, Bonomo K,Trovati M.  Prescription of statins todyslipidemic patients affected byliver diseases: asubtle balance betweenrisks and benefits.Nutr MetabCardiovasc Dis. 2004 Aug;14(4):215-24. PMID:15553600 [PubMed - in process]6:  Hexeberg S, Retterstol K.  [Hypertriglyceridemia--diagnostics, riskandtreatment]Tidsskr Nor Laegeforen. 2004 Nov 4;124(21):2746-9.Review.Norwegian. PMID: 15534665 [PubMed - indexed for MEDLINE]7:  Cheng JW.Rosuvastatin in the management of hyperlipidemia.Clin Ther.2004Sep;26(9):1368-87. PMID: 15531000 [PubMed - in process]8:  Sniderman AD.Is there value in liver function test and creatinephosphokinasemonitoringwith statin use?Am J Cardiol. 2004 Nov4;94(9A):30F-34F. Review.PMID: 15519289 [PubMed - indexed for MEDLINE]9:  Johnson TE, Zhang X,Bleicher KB, Dysart G, Loughlin AF, SchaeferWH,Umbenhauer DR.  Statinsinduce apoptosis in rat and human myotube culturesby inhibitingproteingeranylgeranylation but not ubiquinone.Toxicol ApplPharmacol. 2004 Nov1;200(3):237-50. PMID: 15504460 [PubMed - indexed forMEDLINE]10:  DavidsonMH.  Rosuvastatin safety: lessons from the FDA reviewandpost-approvalsurveillance.Expert Opin Drug Saf. 2004 Nov;3(6):547-57.PMID:15500414 [PubMed - in process]11:  Phillips PS.  Ezetimibe andstatin-associated myopathy.Ann Intern Med.2004 Oct 19;141(8):649. Noabstract available. PMID: 15492351 [PubMed -indexed for MEDLINE]12:Alsheikh-Ali AA, Kuvin JT, Karas RH.  Risk of adverse eventswithfibrates.Am J Cardiol. 2004 Oct 1;94(7):935-8. PMID: 15464682[PubMed -indexed for MEDLINE]13:  Baker SK, Goodwin S, Sur M, Tarnopolsky MA.Cytoskeletal myotoxicityfrom simvastatin and colchicine.Muscle Nerve. 2004Dec;30(6):799-802. PMID:15389652 [PubMed - in process]14:  de Lemos JA,Blazing MA, Wiviott SD, Lewis EF, Fox KA, White HD,RouleauJL, Pedersen TR,Gardner LH, Mukherjee R, Ramsey KE, Palmisano J,Bilheimer DW,Pfeffer MA,Califf RM, Braunwald E; A to Z Investigators.  Earlyintensive vs a delayedconservative simvastatin strategy in patientswithacute coronary syndromes:phase Z of the A to Z trial.JAMA. 2004 Sep15;292(11):1307-16. Epub 2004 Aug30. PMID: 15337732 [PubMed - indexed forMEDLINE]15:  Krivosic-Horber R,Depret T, Wagner JM, Maurage CA.  Malignanthyperthermia susceptibilityrevealed by increased serum creatinekinaseconcentrations during statintreatment.Eur J Anaesthesiol. 2004Jul;21(7):572-4. No abstract available.PMID: 15318472 [PubMed - indexed forMEDLINE]16:  Livingstone C, Al RiyamiS, Wilkins P, Ferns GA.  McArdle's diseasediagnosed followingstatin-induced myositis.Ann Clin Biochem. 2004 Jul;41(Pt4):338-40. PMID:15298748 [PubMed - in process]17:  Chang JT, Staffa JA, Parks M, Green L.Rhabdomyolysis with HMG-CoAreductase inhibitors and gemfibrozilcombinationtherapy.PharmacoepidemiolDrug Saf. 2004 Jul;13(7):417-26. PMID:15269925 [PubMed - indexed forMEDLINE]18:  Carvalho AA, Lima UW, ValienteRA.  Statin and fibrate associatedmyopathy: study of eight patients.ArqNeuropsiquiatr. 2004 Jun;62(2A):257-61.Epub 2004 Jun 23. PMID: 15235728[PubMed - in process]19:  Maggini M, Raschetti R, Traversa G, Bianchi C,Caffari B, Da Cas R,PaneiP.  The cerivastatin withdrawal crisis: a"post-mortem" analysis.HealthPolicy. 2004 Aug;69(2):151-7. PMID: 15212862[PubMed - indexed for MEDLINE]20:  Delgado-Lopez F, Bautista-Lorite J,Villamil-Fernandez F.  [Worseningfor using statin in carnitine palmityoltransferase deficiencymyopathy]RevNeurol. 2004 Jun 1-15;38(11):1095.Spanish. No abstract available. PMID:15202093 [PubMed - indexed forMEDLINE]21:  Takagi A, Shiio Y.  [Pravastatin-associated polymyositis, acasereport]Rinsho Shinkeigaku. 2004 Jan;44(1):25-7.  Japanese. PMID:15199734[PubMed - indexed for MEDLINE]22:  Jamal SM, Eisenberg MJ,Christopoulos S.  Rhabdomyolysis associatedwithhydroxymethylglutaryl-coenzyme A reductaseinhibitors.Am Heart J.2004Jun;147(6):956-65. Review. PMID: 15199341 [PubMed - indexed for MEDLINE]23:Bellosta S, Paoletti R, Corsini A.  Safety of statins: focus onclinicalpharmacokinetics and drug interactions.Circulation. 2004 Jun15;109(23 Suppl1):III50-7. Review. PMID: 15198967 [PubMed - indexed forMEDLINE]24:  LadoLado FL, Rodriguez Moreno C, Cinza Sajurjo S, Duran Parrondo C,PazoNunez M,Lois Pernas A, Masa Vazquez L.  [Statin-induced rhabdomyolysisand renalfailure: also with fluvastatine]An Med Interna. 2004May;21(5):235-7.Spanish. PMID: 15176926 [PubMed - indexed for MEDLINE]25:  Guyton JR.Extended-release niacin for modifying the lipoproteinprofile.Expert OpinPharmacother. 2004 Jun;5(6):1385-98. Review. PMID:15163282 [PubMed -indexed for MEDLINE]26:  Takagi S.  [Neurological complication due to thedrug and the maneuverfor the treatmentand prevention of cerebrovasculardiseases: iatrogenicneurology]Rinsho Shinkeigaku. 2003 Nov;43(11):877-9.Review.  Japanese. PMID:15152491 [PubMed - indexed for MEDLINE]27:Shepherd J.  A prospective study of pravastatin in the elderly at risk:newhope for olderpersons.Am J Geriatr Cardiol. 2004 May-Jun;13(3Suppl1):17-24. Review. PMID: 15133425 [PubMed - indexed for MEDLINE]28:  RandoLP, Cording SA, Newnham HH.  Successful reintroduction of statintherapyafter myositis: was there anothercause?Med J Aust. 2004 May3;180(9):472-3.No abstract available. PMID: 15115429 [PubMed - indexed forMEDLINE]29:Fux R, Morike K, Gundel UF, Hartmann R, Gleiter CH.  Ezetimibeandstatin-associated myopathy.Ann Intern Med. 2004 Apr 20;140(8):671-2.Noabstract available. PMID: 15096354 [PubMed - indexed for MEDLINE]30:  RotenL, Schoenenberger RA, Krahenbuhl S, Schlienger RG.  Rhabdomyolysisinassociation with simvastatin and amiodarone.Ann Pharmacother.2004Jun;38(6):978-81. Epub 2004 Apr 06. PMID: 15069169 [PubMed - indexedforMEDLINE]31:  Fauchais AL, Iba Ba J, Maurage P, Kyndt X, Bataille D,Hachulla E,ParentD, Queyrel V, Lambert M, Michon Pasturel U, Hatron PY,Vanhille P,Devulder B.  [Polymyositis induced or associated withlipid-lowering drugs:five cases]Rev Med Interne. 2004 Apr;25(4):294-8.French. PMID: 15050796[PubMed - indexed for MEDLINE]32:  Scott LJ, CurranMP, Figgitt DP.  Rosuvastatin: a review of its use inthe management ofdyslipidemia.Am J Cardiovasc Drugs. 2004;4(2):117-38.Review. PMID: 15049723[PubMed - indexed for MEDLINE]33:  Moosmann B, Behl C.  Selenoproteinsynthesis and side-effects ofstatins.Lancet. 2004 Mar 13;363(9412):892-4.Review. PMID: 15031036 [PubMed -indexed for MEDLINE]34:  Sinzinger H,O'Grady J.  Professional athletes suffering fromfamilialhypercholesterolaemia rarelytolerate statin treatment because ofmuscularproblems.Br J Clin Pharmacol. 2004 Apr;57(4):525-8. PMID: 15025753[PubMed -indexed for MEDLINE]35:  Koumis T, Nathan JP, Rosenberg JM, Cicero LA.Strategies for theprevention and treatment of statin-induced myopathy:isthere a role forubiquinone supplementation?Am J Health Syst Pharm. 2004Mar 1;61(5):515-9.Review. No abstract available. PMID: 15018231 [PubMed -indexed for MEDLINE]36:  Rosenson RS.  Current overview of statin-inducedmyopathy.Am J Med. 2004Mar 15;116(6):408-16. Review. PMID: 15006590[PubMed - indexed for MEDLINE]37:  Schaefer WH, Lawrence JW, Loughlin AF,Stoffregen DA, Mixson LA, DeanDC,Raab CE, Yu NX, Lankas GR, Frederick CB.Evaluation of ubiquinoneconcentration and mitochondrial function relativetocerivastatin-inducedskeletal myopathy in rats.Toxicol Appl Pharmacol.2004 Jan 1;194(1):10-23.PMID: 14728975 [PubMed - indexed for MEDLINE]38:Andreou ER, Ledger S.  Potential drug interaction between simvastatinanddanazol causingrhabdomyolysis.Can J Clin Pharmacol. 2003Winter;10(4):172-4.PMID: 14712320 [PubMed - indexed for MEDLINE]39:  Jamil S, Iqbal P.Rhabdomyolysis induced by a single dose of astatin.Heart. 2004Jan;90(1):e3. PMID: 14676266 [PubMed - indexed forMEDLINE]40:Riesco-Eizaguirre G, Arpa-Gutierrez FJ, Gutierrez M, Toribio E.[Severepolymyositis with simvastatin use]Rev Neurol. 2003 Nov16-30;37(10):934-6.Spanish. PMID: 14634922 [PubMed - indexed for MEDLINE]41:  Zeman M, Zak A,Vecka M, Romaniv S.  [Long-term hypolipidemic treatmentof mixedhyperlipidemia with a combinationof statins and fibrates]Cas LekCesk. 2003Aug;142(8):500-4.  Czech. PMID: 14626567 [PubMed - indexed forMEDLINE]42:Wang TD, Chen WJ, Lin JW, Cheng CC, Chen MF, Lee YT.  Efficacyoffenofibrate and simvastatin on endothelial function andinflammatorymarkersin patients with combined hyperlipidemia: relations withbaselinelipidprofiles.Atherosclerosis. 2003 Oct;170(2):315-23. PMID: 14612213[PubMed -indexed for MEDLINE]43:  Foody JM, Krumholz HM.  Are statins indicated forthe primary preventionof CAD in octogenarians?antagonist viewpoint.Am JGeriatr Cardiol. 2003Nov-Dec;12(6):357-60. Review. PMID: 14610384 [PubMed -indexed for MEDLINE]44:  Shammas NW, Kapalis MJ, Deckert J, Harris M,Dippel EJ, Labroo A,McKinneyD.  Effectiveness of statin-gemfibrozilcombination therapy inpatients with mixedhyperlipidemia: experience of acommunity lipid clinic andsafety review fromthe literature.Prev Cardiol.2003 Fall;6(4):189-94. PMID:14605512 [PubMed - indexed for MEDLINE]45:Pasternak R.  Ask the doctor. I am a 64-year-old woman with highcholesterolcaused by badgenes (familial hypercholesterolemia). Withoutmedication, mycholesterol isabove 450 mg/dL. So I am taking high-doseLipitor (80 mg/day),WelChol, andZetia to lower my cholesterol. I sometimeshave pain andstiffness in my knees,and my shoulder, elbow, and wrist joints,plus themuscles in between, are stiffin the morning and hurt during the day.Twoyears ago I was diagnosed withbursitis in my hips. Could these problemsbefrom the Lipitor? If so, is thereanother statin I could take thatwouldn'tdo this?Harv Heart Lett. 2003 Oct;14(2):8. No abstract available.PMID:14576039 [PubMed - indexed for MEDLINE]46:  Corsini A.  The safety ofHMG-CoA reductase inhibitors in specialpopulations at highcardiovascularrisk.Cardiovasc Drugs Ther. 2003May;17(3):265-85. Review. PMID: 14574085[PubMed - indexed for MEDLINE]47:  Johi RR, Mills R, Halsall PJ, HopkinsPM.  Anaesthetic management ofcoronary artery bypass grafting in a patientwithcentral core disease andsusceptibility to malignant hyperthermia onstatintherapy.Br J Anaesth. 2003Nov;91(5):744-7. PMID: 14570802 [PubMed -indexed for MEDLINE]48:  Newman CB, Palmer G, Silbershatz H, Szarek M.Safety of atorvastatinderived from analysis of 44 completed trials in9,416patients.Am J Cardiol.2003 Sep 15;92(6):670-6. PMID: 12972104[PubMed - indexed for MEDLINE]49:  Wolszakiewicz J, Bilinska M,Wolkanin-Bartnik J, Piotrowicz R.[Skeletal myopathy associated withconcomitant use of statin and cyclosporinina heart transplant patient -case report]Kardiol Pol. 2002Nov;57(11):446-7.  Polish. PMID: 12961006[PubMed - in process]50:  Luh JY, Karnath BM.  Issues in statin-associatedmyopathy.JAMA. 2003 Aug20;290(7):888; author reply 888-9. No abstractavailable. PMID: 12928463[PubMed - indexed for MEDLINE]51:  Hyman MH.Issues in statin-associated myopathy.JAMA. 2003 Aug20;290(7):888; authorreply 888-9. No abstract available. PMID: 12928462[PubMed - indexed forMEDLINE]52:  Kiortsis DN, Nikas S, Hatzidimou K, Tsianos E, Elisaf MS.Lipid-loweringdrugs and serum liver enzymes: the effects of body weightandbaseline enzymelevels.Fundam Clin Pharmacol. 2003 Aug;17(4):491-4. PMID:12914553 [PubMed -indexed for MEDLINE]53:  [No authors listed]  Statins:new data in secondary prevention anddiabetes. Pravastatin andsimvastatinare the best-assessed statins.PrescrireInt. 2003 Aug;12(66):143-8. PMID:12908497 [PubMed - indexed for MEDLINE]54:  Muller T.  [Statin-inducedParkinson's-syndrome. Reader's letter on thearticle by J.Finsterer in "DerNervenarzt" (2003) 74:115-122]Nervenarzt. 2003Aug;74(8):726-7. Epub 2003May 10.  German. No abstractavailable. PMID:12904874 [PubMed - indexed forMEDLINE]55:  Bannwarth B.  Drug-induced myopathies.Expert Opin Drug Saf.2002May;1(1):65-70. Review. PMID: 12904161 [PubMed - indexed for MEDLINE]56:  Davidson MH.  Controversy surrounding the safety ofcerivastatin.ExpertOpin Drug Saf. 2002 Sep;1(3):207-12. Review. PMID:12904136 [PubMed -indexed for MEDLINE]57:  Jacobson TA.  Combination lipid-lowering therapywith statins: safetyissues in thepostcerivastatin era.Expert Opin Drug Saf.2003 May;2(3):269-86.Review. PMID: 12904106 [PubMed - indexed for MEDLINE]58:  Ito MK.  Advances in the understanding and management ofdyslipidemia:usingniacin-based therapies.Am J Health Syst Pharm. 2003 Jul1;60(13 Suppl2):S15-21; quiz S25. PMID: 12901026 [PubMed - indexed forMEDLINE]59:Clotet B, Negredo E.  HIV protease inhibitors and dyslipidemia.AIDSRev.2003 Jan-Mar;5(1):19-24. Review. PMID: 12875104 [PubMed - indexedforMEDLINE]60:  Arenas J, Martin MA.  [Metabolic intolerance toexercise]Neurologia.2003 Jul-Aug;18(6):291-302. Review.  Spanish. PMID:12838448 [PubMed -indexed for MEDLINE]61:  Andrejak M, Gras V, Massy ZA,Caron J.  [Adverse effects ofstatins]Therapie. 2003 Jan-Feb;58(1):77-83.Review.  French. PMID: 12822204[PubMed - indexed for MEDLINE]62:  Liem AH,Jukema JW, van Veldhuisen DJ.  Secondary prevention in coronaryheartdisease patients with low HDL: whichoptions do we have?Int J Cardiol.2003Jul;90(1):15-21. Review. PMID: 12821213 [PubMed - indexed for MEDLINE]63:Teichholz LE.  Statin-associated myopathy with normal creatinekinaselevels.Ann Intern Med. 2003 Jun 17;138(12):1008; author reply 1008-9.Noabstractavailable. PMID: 12809468 [PubMed - indexed for MEDLINE]64:Torgovnick J, Arsura E.  Statin-associated myopathy with normalcreatinekinase levels.Ann Intern Med. 2003 Jun 17;138(12):1007; author reply1008-9.No abstractavailable. PMID: 12809467 [PubMed - indexed for MEDLINE]65:Hyman MH.  Statin-associated myopathy with normal creatine kinaselevels.AnnIntern Med. 2003 Jun 17;138(12):1007; author reply 1008-9.Noabstractavailable. PMID: 12809466 [PubMed - indexed for MEDLINE]66:  TomaE, Loignon M.  Statin-associated myopathy with normal creatinekinaselevels.Ann Intern Med. 2003 Jun 17;138(12):1007-8; author reply1008-9. Noabstractavailable. PMID: 12809465 [PubMed - indexed for MEDLINE]67:  OrnatoJP.  Should you worry about the side effects of statins? Statindose,health, andother drugs affect side-effect risk.Health News.2003Jun;9(6):1-2. No abstract available. PMID: 12793395 [PubMed - indexedforMEDLINE]68:  Davidson MH.  Combination lipid-lowering therapy indiabetes.Curr DiabRep. 2003 Jun;3(3):263-8. Review. PMID: 12762976[PubMed - indexed forMEDLINE]69:  Schmitz G, Drobnik W.  Pharmacogenomicsand pharmacogenetics ofcholesterol-lowering therapy.Clin Chem Lab Med. 2003Apr;41(4):581-9. Review.PMID: 12747606 [PubMed - indexed for MEDLINE]70:Worz CR, Bottorff M.  Treating dyslipidemic patients withlipid-modifyingand combination therapies.Pharmacotherapy. 2003May;23(5):625-37. Review.PMID: 12741437 [PubMed - indexed for MEDLINE]71:  Bays H, Dujovne C.Colesevelam HCl: a non-systemic lipid-alteringdrug.Expert OpinPharmacother. 2003 May;4(5):779-90. Review. PMID: 12740000[PubMed - indexedfor MEDLINE]72:  Paragh G, Balogh Z, Romics L.  [Antilipemic therapyandrhabdomyolysis]Orv Hetil. 2003 Mar 16;144(11):515-20. Review.Hungarian.PMID: 12731338 [PubMed - indexed for MEDLINE]73:  Gotto AM Jr.  Risks andbenefits of continued aggressive statintherapy.Clin Cardiol. 2003 Apr;26(4Suppl 3):III3-12. Review. PMID: 12708633[PubMed - indexed for MEDLINE]74:Thompson PD, Clarkson P, Karas RH.  Statin-associated myopathy.JAMA.2003Apr 2;289(13):1681-90. Review. PMID: 12672737 [PubMed - indexed forMEDLINE]75:Braun RN, Halhuber MJ, Hitzenberger G.  [Information regardingadversedrug effects and treatment indications ("packageinserts") exemplifiedbycervistatin (Lipobay)]Wien Med Wochenschr. 2003;153(3-4):80-2.German.PMID: 12658968 [PubMed - indexed for MEDLINE]76:  Lee TH.  Ask the doctor.At age 62 I'm a bit overweight and havediabetes. I take astatin, and my LDLcholesterol is good (84 mg/dL). But myHDL is low (30 mg/dL)and mytriglycerides are above 300 mg/dL. Are hightriglycerides a problem?HarvHeart Lett. 2003 Mar;13(7):8. No abstractavailable. PMID: 12654588[PubMed - indexed for MEDLINE]77:  [No authors listed]  How a statin mightdestroy a drug company.Lancet.2003 Mar 8;361(9360):793. No abstractavailable. PMID: 12642039 [PubMed -indexed for MEDLINE]78:  Smith CC,Bernstein LI, Davis RB, Rind DM, Shmerling RH.  Screening forstatin-relatedtoxicity: the yield of transaminase and creatinekinasemeasurements in aprimary care setting.Arch Intern Med. 2003 Mar24;163(6):688-92. PMID:12639201 [PubMed - indexed for MEDLINE]79:  Gotto AM Jr.  Safety and statintherapy: reconsidering the risks andbenefits.Arch Intern Med. 2003 Mar24;163(6):657-9. No abstract available.PMID: 12639194 [PubMed - indexed forMEDLINE]80:  Ballantyne CM, Corsini A, Davidson MH, Holdaas H, JacobsonTA,LeitersdorfE, Marz W, Reckless JP, Stein EA.  Risk for myopathy withstatintherapy in high-risk patients.Arch Intern Med. 2003 Mar10;163(5):553-64.Review. PMID: 12622602 [PubMed - indexed for MEDLINE]81:  Bennett WE, DrakeAJ 3rd, Shakir KM.  Reversible myopathy after statintherapy in patientswith normal creatinekinase levels.Ann Intern Med. 2003Mar 4;138(5):436-7.No abstract available. PMID: 12614104 [PubMed - indexedfor MEDLINE]82:Farmer JA.  Statins and myotoxicity.Curr Atheroscler Rep.2003Mar;5(2):96-100. Review. PMID: 12573193 [PubMed - indexed for MEDLINE]83:Glueck CJ, Streicher P.  Cardiovascular and medical ramificationsoftreatment of subclinicalhypothyroidism.Curr Atheroscler Rep.2003Jan;5(1):73-7. Review. PMID: 12562546 [PubMed - indexed for MEDLINE]84:Sinzinger H.  Statin-induced myositis migrans.Wien Klin Wochenschr. 2002Nov30;114(21-22):943-4. PMID: 12528328 [PubMed - indexed for MEDLINE]85:  YimBT, Chong PH.  Niacin-ER and lovastatin treatment ofhypercholesterolemiaand mixeddyslipidemia.Ann Pharmacother. 2003Jan;37(1):106-15. Review. PMID:12503944 [PubMed - indexed for MEDLINE]86:  Gazarin S, Abd-El-Hady H,Gheith O, Rasem M, Saad M, El-Sayed K, SobhM,Amer G.  Neuromusculartoxicity in nephrotic patients treated withfluvastatin.J Nephrol. 2002Nov-Dec;15(6):690-5. PMID: 12495286 [PubMed -indexed for MEDLINE]87:Black C, Jick H.  Etiology and frequency ofrhabdomyolysis.Pharmacotherapy.2002 Dec;22(12):1524-6. PMID: 12495162[PubMed - indexed for MEDLINE]88:Xydakis AM, Ballantyne CM.  Combination therapy for combineddyslipidemia.AmJ Cardiol. 2002 Nov 20;90(10B):21K-29K. Review. PMID:12467937 [PubMed -indexed for MEDLINE]89:  Mantel-Teeuwisse AK, Klungel OH, Herings RM, vanPuijenbroek EP,PorsiusAJ, de Boer A.  Myopathy due to statin/fibrate use intheNetherlands.Ann Pharmacother. 2002 Dec;36(12):1957-60. PMID:12452761[PubMed - indexed for MEDLINE]90:  Bolego C, Baetta R, Bellosta S, CorsiniA, Paoletti R.  Safetyconsiderations for statins.Curr Opin Lipidol. 2002Dec;13(6):637-44. Review.PMID: 12441888 [PubMed - indexed for MEDLINE]91:Prasad GV, Wong T, Meliton G, Bhaloo S.  Rhabdomyolysis due to redyeastrice (Monascus purpureus) in a renaltransplantrecipient.Transplantation.2002 Oct 27;74(8):1200-1. PMID: 12438974[PubMed - indexed for MEDLINE]92:Kind AH, Zakowski LJ, McBride PE.  Rhabdomyolysis from the combination ofastatin and gemfibrozil: an uncommonbut serious adversereaction.WMJ.2002;101(7):53-6. PMID: 12426921 [PubMed - indexed for MEDLINE]93:Schuff-Werner P, Kohlschein P.  [Current therapy ofhypercholesterolemia.How much statin does your patientneed?]MMW FortschrMed. 2002 Aug8;144(31-32):24-6.  German. PMID: 12422725 [PubMed - indexedfor MEDLINE]94:  Hare CB, Vu MP, Grunfeld C, Lampiris HW.Simvastatin-nelfinavirinteraction implicated in rhabdomyolysis anddeath.Clin Infect Dis. 2002 Nov15;35(10):e111-2. Epub 2002 Oct 25. PMID:12410494 [PubMed - indexed forMEDLINE] 95:  Phillips PS, Haas RH, Bannykh S,Hathaway S, Gray NL, KimuraBJ, VladutiuGD, England JD; Scripps MercyClinical Research Center.Statin-associated myopathy with normal creatinekinase levels.Ann InternMed. 2002 Oct 1;137(7):581-5. PMID: 12353945[PubMed - indexed for MEDLINE]96:  Lewin JJ 3rd, Nappi JM, Taylor MH.Rhabdomyolysis with concurrentatorvastatin and diltiazem.Ann Pharmacother.2002 Oct;36(10):1546-9. PMID:12243603 [PubMed - indexed for MEDLINE] 97:Sinzinger H, Chehne F,Lupattelli G.  Oxidation injury in patients receivingHMG-CoA reductaseinhibitors: occurrencein patients without enzyme elevationor myopathy.DrugSaf. 2002;25(12):877-83. PMID: 12241128 [PubMed - indexedfor MEDLINE] 98:Aboulafia DM, Johnston R.  Simvastatin-inducedrhabdomyolysis in anHIV-infected patient with coronaryartery disease.AIDSPatient Care STDS.2000 Jan;14(1):13-8. PMID: 12240878 [PubMed - indexed forMEDLINE] 99:Vivekananthan K, Mehra MR, Uber PA, DeGruiter H, Lavie CJ,Milani RV.Comparison of the efficacy and safety of pravastatin andsimvastatin inhearttransplantation.J Assoc Physicians India. 2002May;50(5):682-4. PMID:12186124 [PubMed - indexed for MEDLINE] 100:  Evans M,Rees A.  Effects ofHMG-CoA reductase inhibitors on skeletal muscle: are allstatinsthesame?Drug Saf. 2002;25(9):649-63. Review. PMID: 12137559[PubMed -indexed for MEDLINE] 101:  Sinzinger H, Wolfram R, Peskar BA.Muscular sideeffects of statins.J Cardiovasc Pharmacol. 2002Aug;40(2):163-71. Review.PMID: 12131545 [PubMed - indexed for MEDLINE] 102:Heart Protection StudyCollaborative Group.  MRC/BHF Heart Protection Studyof cholesterol loweringwith simvastatin in20,536 high-risk individuals: arandomisedplacebo-controlled trial.Lancet. 2002 Jul 6;360(9326):7-22.Summary forpatients in: Curr Cardiol Rep.2002 Nov;4(6):486-7. PMID: 12114036[PubMed -indexed for MEDLINE] 103:  Bae J, Jarcho JA, Denton MD, Magee CC.Statinspecific toxicity in organ transplant recipients: case report andreviewofthe literature.J Nephrol. 2002 May-Jun;15(3):317-9. Review. PMID:12113605[PubMed - indexed for MEDLINE] 104:  de Sauvage Nolting PR, BuirmaRJ,Hutten BA, Kastelein JJ; Dutch ExPRESSInvestigator Group.  Two-yearefficacyand safety of simvastatin 80 mg in familialhypercholesterolemia(theExamination of Probands and Relatives in StatinStudies WithFamilialHypercholesterolemia [ExPRESS FH]).Am J Cardiol. 2002 Jul15;90(2):181-4. Noabstract available. PMID: 12106856 [PubMed - indexed forMEDLINE] 105:Liamis G, Kakafika A, Bairaktari E, Miltiadous G, TsimihodimosV,GoudevenosJ, Achimastos A, Elisaf M.  Combined treatment with fibrates andsmall dosesof atorvastatin in patientswith mixed hyperlipidemia.Curr Med ResOpin.2002;18(3):125-8. PMID: 12094821 [PubMed - indexed for MEDLINE]106:Williams D, Feely J.  Pharmacokinetic-pharmacodynamic drug interactionswithHMG-CoA reductaseinhibitors.Clin Pharmacokinet. 2002;41(5):343-70.Review.PMID: 12036392 [PubMed - indexed for MEDLINE] 107:  Sinzinger H.Flu-likeresponse on statins.Med Sci Monit. 2002 May;8(5):CR384-8. PMID:12011782[PubMed - indexed for MEDLINE] 108:  [No authors listed]Statinstories.Diabetes Obes Metab. 2002 Mar;4(2):138. No abstract available.PMID:11993442 [PubMed - indexed for MEDLINE] 109:  Maxa JL, Melton LB, OguCC,Sills MN, Limanni A.  Rhabdomyolysis after concomitant use ofcyclosporine,simvastatin, gemfibrozil,and itraconazole.Ann Pharmacother.2002May;36(5):820-3. PMID: 11978159 [PubMed - indexed for MEDLINE] 110:FoxtonJ.  Statin safety.Nurs Stand. 2001 Sep 19-25;16(1):20. Noabstractavailable. PMID: 11977679 [PubMed - indexed for MEDLINE] 111:Gensini GF,Conti AA, Conti A, Panti A.  [From prevention tocardiovascularrehabilitation: statins and evidence-basedmedicine]Ital HeartJ Suppl. 2002Jan;3(1):91-4. Review.  Italian. PMID: 11899580 [PubMed -indexed forMEDLINE] 112:  Sica DA, Gehr TW.  3-Hydroxy-3-methylglutarylcoenzyme Areductase inhibitors and rhabdomyolysis:considerations in therenal failurepatient.Curr Opin Nephrol Hypertens. 2002 Mar;11(2):123-33.Review. PMID:11856903 [PubMed - indexed for MEDLINE] 113:  Omar MA, WilsonJP.  FDAadverse event reports on statin-associated rhabdomyolysis.AnnPharmacother.2002 Feb;36(2):288-95. Review. PMID: 11847951 [PubMed - indexedfor MEDLINE]114:  Prieto JC.  [Safety profile of statins]Rev Med Chil.2001Nov;129(11):1237-40.  Spanish. PMID: 11836874 [PubMed - indexed forMEDLINE]115:  Sica DA, Gehr TW.  Rhabdomyolysis and statin therapy:relevance to theelderly.Am J Geriatr Cardiol. 2002 Jan-Feb;11(1):48-55.Review. PMID:11773716 [PubMed - indexed for MEDLINE] 116:  Banga JD.[Myotoxicity andrhabdomyolisis due to statins]Ned Tijdschr Geneeskd. 2001Dec8;145(49):2371-6. Review.  Dutch. PMID: 11770264 [PubMed - indexedforMEDLINE] 117:  Hamilton-Craig I.  Statin-associated myopathy.Med JAust.2001 Nov 5;175(9):486-9. Review. PMID: 11758079 [PubMed - indexedforMEDLINE] 118:  Bernini F, Poli A, Paoletti R.  Safety of HMG-CoAreductaseinhibitors: focus on atorvastatin.Cardiovasc Drugs Ther.2001;15(3):211-8.Review. 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