There was at that time a dearth of information.  The Statin Adverse Effects
FAQ now goes 81 pages, with a Table of Contents.

It is limited to published medical journal articles showing adverse effects
of statins.  Only a few of those are anecdotal.  Not one alleges conspiracy,
nor do I.

Which of these journals are you accusing of publishing conspiracy theories?
Which is substituting science, and with what?

Statin Adverse Effects - Frequently Asked Questions (FAQ)

Table of Contents

Where can I look to find information on research studies of statin drugs?
........................  2

STATINS & MITOCHONDRIAL CYTOPATHY, COENZYME Q10 (UBIQUINONE)

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

Erectile Dysfunction And Statin Therapy: Interaction With Cardiovascular
Risk

Frequently Asked Question: Do statins cause muscle damage, muscle pain,
myopathy,

Why are most studies so positive about statins, and why are there relatively
so few

published that show problems?  Do Medical Journals agree that there is bias
in drug-

Are there any books on the topic?
.......................................................................................
5

United States Adverse Events reporting
.....................................................................  7

Canadian Adverse Events reporting
............................................................................
7

Australian Adverse Events reporting
..........................................................................
7

British Adverse Events reporting
................................................................................
7

All Countries: Report Adverse Events to the UCSD Statin Study
.............................  8

How should I ask my doctor to report statin adverse effects?
....................................  8

OK, what references should I take to my doctor?
...............................................................  9

NERVE DAMAGE & STATINS
.......................................................................................
9

DEFICIENCY CAUSED BY STATINS
..........................................................................
21

STATIN BIRTH DEFECTS
.............................................................................................
28

children?
........................................................................................................................
28

ERECTILE DYSFUNCTION (ED) AND STATINS
......................................................  32

Factors And Drug Therapies
.........................................................................................
32

LUPUS-LIKE SYMPTOMS AND STATINS
.................................................................  34

MYOPATHY AND STATINS
.........................................................................................
36

myositis, and muscle cell death (apoptosis) with or without elevated CK?
.................  36

RHABDOMYOLYSIS AND STATINS
..........................................................................
60

Frequently Asked Question: Which statins cause deadly Rhabdomyolysis?
...............  61

STATINS AND LIVER OR KIDNEY DAMAGE
..........................................................  75

Frequently Asked Question: Do statins damage liver or kidneys?
...............................  75

ELDERLY AND STATINS
.............................................................................................
77

IS  THERE AN INDUSTRY BIAS IN STATIN PUBLICATIONS?
...............................  78

industry funded medical studies?
..................................................................................
78

Updated 7February 2005:

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_PRO
DUCT_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 prostatin 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?

United States Adverse Events reporting

Report to the FDA, http://www.fda.gov/medwatch/how.htm

Canadian Adverse Events reporting

Health Canada:

http://www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/index_adverse_report_e.html

PharmaWatch:

http://www.pharmawatch.net/

Australian Adverse Events reporting

Australian Adverse Drug Reaction Reporting System

http://www.tgasime.health.gov.au/SIME/ADRS/ADRSRepo.nsf?OpenDatabase

British Adverse Events reporting

PRODIGY Guidance - Adverse drug reactions, Practical Support for Clinical
Governance
http://www.prodigy.nhs.uk/guidance.asp?gt=Adverse%20drug%20reactions

All Countries: Report Adverse Events to the UCSD Statin Study

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/

How should I ask my doctor to report statin adverse effects?

Here is an example letter to your physician.  You can customize it any way
you wish, including adding your name and signature, the doctor's name and
the date. Print it out and take it with you to your next appointment, with
the references in this FAQ that relate to your symptoms:

To my physician,

I believe that my symptoms may be due to the adverse effects a_ssociated
with cholesterol-lowering statin drugs.  I need your help to understand the
cause of my symptoms, treatment options, and the prognosis for my recovery.

Please review the references below, published medical studies that show
similar problems a_ssociated with statin drugs.  These are made available
via the National Institutes of Health (NIH,
http://www.ncbi.nlm.nih.gov/Entrez/) library of biomedical journal citations
and other major repositories of medical research.

Also, I am respectfully requesting that you file an adverse effects report
with the FDA (http://www.fda.gov/medwatch/how.htm), and that you please send
a copy of the report to the to the NIH-funded Statin Study, attention: Dr.

Beatrice Golomb, Principal Investigator. Statin Study website:
http://medicine.ucsd.edu/statin/ Statin Study contact info:
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

OK, what references 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.

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

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=Abstr
act&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=Abstr
act&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=Abstr
act&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=Abstr

act&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)

Am J Med. 2004 Dec 1;117(11):823-9.

Randomized trial of the effects of simvastatin on cognitive functioning in

hypercholesterolemic adults.

Muldoon MF, Ryan CM, Sereika SM, Flory JD, Manuck SB.

Center for Clinical Pharmacology, University of Pittsburgh, Pennsylvania
15260, USA.

mfm10@pitt.edu

"This study provides partial support for minor decrements in cognitive
functioning with

statins. Whether such effects have any long-term sequelae or occur with
other

cholesterol-lowering interventions is not known." This is the second of two
studies by

Muldoon, both showing measurable cognitive decline in statin groups after
only 6

months, using Neuropsych testing.  Further, the cognitive deficits appear
consistently in

specific areas.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstr

act&list_uids=15589485

Muldoon MF, Ryan CM, Flory JD, Manuck SB (2002),

Effects of simvastatin on cognitive functioning.

Presented at the American Heart Association Scientific

Sessions. Chicago; Nov. 17-20.

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, nearly 100% of the patients on placeboes showed a measurable
increase in

cognitive function, and nearly 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

Cognitive impairment associated with atorvastatin and simvastatin.

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

Department of Medicine, University of Mississippi Medical Center, Jackson,
Mississippi

39216, USA. dking@pharmacy.umsmed.edu

Pharmacotherapy. 2003 Dec;23(12):1663-7.

"we report two women who experienced significant cognitive impairment
temporally

related to statin therapy. One woman took atorvastatin, and the other first
took

atorvastatin, then was rechallenged with simvastatin. Clinicians should be
aware of

cognitive impairment and dementia as potential adverse effects associated
with statin

therapy."  PMID: 14695047

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstr

act&list_uids=14695047

Cognitive impairment associated with atorvastatin.

King DS, Jones DW, Wofford MR et al. (2001), Presented at the American
College of

Clinical Pharmacy Spring Practice and Research Forum. Salt Lake City; April
22-25.

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

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 nearly 100%
of statin users had a

measurable loss of cognitive ability after 6 months, while nearly 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

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=PXke2H8h99pyNVS
CajAh5clptzOAHJSZuNBobSwWmi9veWjdJ2A3%7C-1468812056489609316/184161392/6/7001/7001/7002/7002/7001/-1

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

ADR of the Month  September 2001 Vol. 6 No. 9  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:

1. 14. Orsi A, Sherman O, Woldeselassie Z. Simvastatin-associated memory
loss.

2. 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
statinassociated 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 for
statin-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."

STATINS & MITOCHONDRIAL CYTOPATHY, COENZYME Q10 (UBIQUINONE) DEFICIENCY
CAUSED BY STATINS

Frequently Asked Question: What is this I hear about statins causing a
Coenzyme Q10 deficiency and damaging the cellular mitochondria so my muscle
cells cannot breathe?

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
of coenzyme 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
risk for 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 I take 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 for
statin-induced changes in diastolic LV performance: description of a
clinical protocol. 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 affecting
other 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
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]

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
combined with 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 oxidative
phosphorylation. 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 randomized placebo-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 abstract
available. 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
abstract available. 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
abstract available. 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+statin

+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

Frequently Asked Question: What other deficiencies can statin drugs cause?

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

Note, some later reports discount this study, but to be safe, your doctor
should closely monitor any withdrawl from statins.

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:

Golomb BA, Kane T, Dimsdale JA (2004), Severe irritability associated with
statin

cholesterol-lowering drugs. QJM 97(4):229-235.

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&search_fulltext=&sp-

p=All&search_volume=&search_startpage=&search_title=&search_author=&search_abs

tract=statins+as+immunosuppressors&issue_start_month=12&issue_start_year=2000&is

sue_end_month=01&issue_end_year=2001&pickerCount=You+have+selected+1+journa

l+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 Cell Diabetes Centre,Chelsea & Westminster Hospital, 3Department of Chemical Pathology, St.Thomas' Hospital, LondonUKErectile dysfunction has been associated with atherosclerotic risk factorsand drugs used in their treatment. This study investigated the relationshipof erectile function with cardiovascular risk factors and specific drugtherapies. International Index of Erectile Function (IIEF) scores measuredin 100 men attending cardiovascular risk clinics. Cardiovascular riskfactors and drug therapies were assessed prior to initation and after 6months of statin therapy. Before statin therapy no correlation was observedbetween IIEF score and any individual cardiovascular risk factor thoughbetter scores were observed in patients on warfarin or angiotensin-IIreceptor blocker therapy (r=0.42; p <0.001). After 6 months of statintherapy, significant correlations were observed 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 of statin prescribed showed nocorrelation with change in IIEF score. This study suggests impotencefollowing statin therapy is likelier in patients with more severeendothelial dysfunction due to established cardiovascular risk factorsincluding age, and smoking and diabetes. This is complicated by adverseinteractions between statin therapy and concomitant treatment with warfarinor angiotensin-II type I receptor blockers.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, principal investigator of a study on Statin Drugs by the NationalInstitutes of Health. Dr. Golomb noted that the most common problemsreported about statin drugs pertain to muscle pain or weakness, fatigue,memory and cognitive problems, sleep problems, and neuropathy. Erectiledysfunction, problems with temperature regulation (feeling hot or cold, orhaving sweats) are among the other problems reported. "http://www.coloradohealthsite.org/pharmacology/statins.html"Question: What are the common complaints of patients who take statins?Dr. Golomb: The most common problems we hear reported pertain to muscle painor weakness, fatigue, memory and cognitive problems, sleep problems, andneuropathy. Erectile dysfunction, problems with temperature regulation(feeling hot or cold, or having sweats), are among the other problemsreported. "http://www.coloradohealthsite.org/topics/interviews/golomb.htmlBBC News: Wednesday, 15 March, 2000, 19:02 GMT Heart drug impotence warning"Statins prevent heart attacks by reducing the levels of dangerouscholesterol in the bloodstream.  However, a small number of men prescribed the life-saving drug havecomplained that they are unable to achieve an erection.""Dr John Harvey, from the Wrexham Maelor Hospital in Wales, identified 220men who appeared to have lost their "virility" after starting to takestatins. "http://news.bbc.co.uk/1/hi/health/678811.stmBailey DG, Dresser GK.  Interactions between grapefruit juice and cardiovascular drugs. Am JCardiovasc 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 a cohort of type IIdiabetes 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-induced lupus-like syndrome associated with severe autoimmunehepatitis.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 andother members of the statin family are widely used for the treatment ofhypercholesterolaemia in order to reduce the risk of atherosclerosis andcardiovascular disease. Atorvastatin-induced adverse events are mostly mildand only a few cases of lupus-like syndrome or severe acute hepatitis havebeen documented. In this case report we describe a patient who developed anatorvastatin-induced severe autoimmune hepatitis. In addition, this patientpresented with a concomitant systemic lupus-like syndrome which has beenalready described for statins but not in association with severe liverdisease. Although the drug was immediately withdrawn the disease persistedand even deteriorated to a fulminant disease with evidence of acute hepaticfailure. The patient failed to respond to conventional immunosuppressionwith corticosteroids and azathioprine. Only the introduction of intenseimmunosuppressive therapy, as used in solid organ transplantation, led to acomplete and sustained recovery of the patient.Interestingly, the patient was HLA DR3- and HLA DR4-positive, which arewell-known genetic factors associated with autoimmune diseases. This case isthe first report of a drug-induced lupus-likesyndrome concomitant with asevere autoimmune hepatitis in a genetically predisposed patient."Noel B, Panizzon RG.  Lupus-like syndrome associated with statin therapy. Dermatology.2004;208(3):276-7.  PMID: 15118389 [PubMed - indexed for MEDLINE] "Statinsare among the most widely prescribed drugs. An increasing number oflupus-like syndrome has recently been reported with these lipid-loweringagents. We describe a new case associated with simvastatin therapy. Thepresence of anti-dsDNA antibodies in the serum is for the first timereported confirming that statins may also induce a systemic autoimmunereaction. Statin-induced lupus-like syndrome is characterized by the longdelay between the beginning of therapy and the skin eruption. Antinuclearantibodies may persist for many months after drug discontinuation. Thecausal relationship may be therefore difficult to establish, and probablymany cases are unrecognized. Early diagnosis may avoid unnecessaryimmunosuppressive therapy. Copyright 2004 S. Karger AG, Basel"Lantuejoul S, Brambilla E, Brambilla C, Devouassoux G.  Statin-induced fibrotic nonspecific interstitial pneumonia. Eur Respir J.2002 Mar;19(3):577-80. PMID: 11936540 [PubMed - indexed for MEDLINE]"Statins inhibit the 3-hydroxy-3-methylglutaryl coenzyme A reductase, reducethe serum level of low-density lipoprotein cholesterol, and are extensivelyprescribed to prevent cardiovascular mortality and morbidity. Few systemicadverse effects, such as pseudopolymyositis, lupus-like syndromes, andanecdotal hypersensitivity pneumonitis, have been reported. Asimvastatin-induced diffuse interstitial pneumonia associated with anonspecific interstitial pneumonia pattern at histological analysis isrepoted here. Ultrastructural analysis showed a diffuse cytoplasmicaccumulation of intralysosomial lamellar inclusions in type IIpneumonocytes, histiocytes and endothelial cells, suggesting a sharedpathogenesis with amphiphilic drug-induced toxic lung injury. Becausestatins are increasingly prescribed, statin-induced interstitial lungdisorders may be more frequently observed and early recognition will berequired."Chazerain P, Hayem G, Hamza S, Best C, Ziza JM.  Four cases of tendinopathy in patients on statin therapy. Joint BoneSpine. 2001 Oct;68(5):430-3.  PMID: 11707010 [PubMed - indexed for MEDLINE]"During the last decade, statins have been widely prescribed aslipid-lowering drugs. Their overall safety profile is good. The mainmusculoskeletal side effects have consisted of muscle pain and weakness,peripheral neuropathy, and a few cases of drug-induced lupus. We report thefirst four cases of tendinopathy in patients receiving statin therapy. Therewere three men and one woman. The diagnoses were extensortenosynovitis atthe hands (case 1), tenosynovitis of the tibialis anterior tendon (case 2),and Achilles tendinopathy (cases 3 and 4). Two patients were on simvastatinand two on atorvastatin. The tendinopathy developed 1 to 2 months aftertreatment initiation. The outcome was consistently favorable within 1 to 2months after discontinuation of the drug. Similar cases have been reportedto French pharmacovigilance centers. This report of four cases oftendinopathy draws attention to a possible and heretofore unrecognized sideeffect of a drug class that is becoming increasingly popular. Statins areeffective in lowering high cholesterol levels in patients with type IIa orIIb hypercholesterolemia. They have been widely used for the last decade,particularly in the secondary and primary prevention of major coronaryevents. Statins act by inhibiting the enzymehydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase. Although mostpatients tolerate statins extremely well, a few experience side effectsrequiring treatment discontinuation. Reported musculoskeletal side effectsinclude 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, muscle pain,myopathy, myositis, and muscle cell death (apoptosis) with or withoutelevated CK?1: Phillips PS.  Ezetimibe and statin-associated myopathy. Ann Intern Med. 2004 Oct19;141(8):649. No abstract available.  PMID: 15492351 [PubMed - indexed forMEDLINE]2: Phillips PS, Phillips CT, Sullivan MJ, Naviaux RK, Haas RH.  Statin myotoxicity is associated with changes in the cardiopulmonaryfunction. Atherosclerosis. 2004 Nov;177(1):183-8. PMID: 15488882 [PubMed -in process]3: Phillips PS, Haas RH, Bannykh S, Hathaway S, Gray NL, Kimura BJ, VladutiuGD, England JD; Scripps Mercy Clinical Research Center.  Statin-associated myopathy with normal creatine kinase levels. Ann InternMed. 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 under therapy with lipid-lowering agents.] Nervenarzt. 2004 Dec18; [Epub ahead of print] German.PMID: 15609055 [PubMed - as supplied by publisher]2: [No authors listed] A warning about one statin at a high dose. Heart Advis. 2004 Nov;7(11):2.No abstract available.  PMID: 15580669 [PubMed - indexed for MEDLINE]3: Graham DJ, Staffa JA, Shatin D, Andrade SE, Schech SD, La Grenade L,Gurwitz JH, Chan KA, Goodman MJ, Platt R.  Incidence of hospitalized rhabdomyolysis in patients treated withlipid-lowering drugs. JAMA. 2004 Dec 1;292(21):2585-90. Epub 2004 Dec 1.PMID: 15572716 [PubMed - indexed for MEDLINE]4: [No authors listed] Safety of aggressive statin therapy. Med Lett Drugs Ther. 2004 Nov22;46(1196):93-5. PMID: 15557874 [PubMed - indexed for MEDLINE]5: Anfossi G, Massucco P, Bonomo K, Trovati M.  Prescription of statins to dyslipidemic patients affected by liverdiseases: a subtle balance between risks and benefits. Nutr Metab CardiovascDis. 2004 Aug;14(4):215-24. PMID: 15553600 [PubMed - in process]6: Hexeberg S, Retterstol K.  [Hypertriglyceridemia--diagnostics, risk and treatment] Tidsskr NorLaegeforen. 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 creatine phosphokinasemonitoring with statin use? Am J Cardiol. 2004 Nov 4;94(9A):30F-34F. Review.PMID: 15519289 [PubMed - indexed for MEDLINE]9: Johnson TE, Zhang X, Bleicher KB, Dysart G, Loughlin AF, Schaefer WH,Umbenhauer DR.  Statins induce apoptosis in rat and human myotube cultures by inhibitingprotein geranylgeranylation but not ubiquinone. Toxicol Appl Pharmacol. 2004Nov 1;200(3):237-50.PMID: 15504460 [PubMed - indexed for MEDLINE]10: Davidson MH.  Rosuvastatin safety: lessons from the FDA review and post-approvalsurveillance. Expert Opin Drug Saf. 2004 Nov;3(6):547-57.  PMID: 15500414[PubMed - in process]11: Phillips PS.  Ezetimibe and statin-associated myopathy. Ann Intern Med. 2004 Oct19;141(8):649. No abstract available.  PMID: 15492351 [PubMed - indexed forMEDLINE]12: Alsheikh-Ali AA, Kuvin JT, Karas RH.  Risk of adverse events with fibrates. Am J Cardiol. 2004 Oct1;94(7):935-8.  PMID: 15464682 [PubMed - indexed for MEDLINE]13: Baker SK, Goodwin S, Sur M, Tarnopolsky MA.  Cytoskeletal myotoxicity from simvastatin and colchicine. Muscle Nerve.2004 Dec;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, BilheimerDW, Pfeffer MA, Califf RM, Braunwald E; A to Z Investigators.  Early intensive vs a delayed conservative simvastatin strategy in patientswith acute coronary syndromes: phase Z of the A to Z trial. JAMA. 2004 Sep15;292(11):1307-16. Epub 2004 Aug 30. PMID: 15337732 [PubMed - indexed forMEDLINE]15: Krivosic-Horber R, Depret T, Wagner JM, Maurage CA.  Malignant hyperthermia susceptibility revealed by increased serum creatinekinase concentrations during statin treatment. Eur J Anaesthesiol. 2004Jul;21(7):572-4. No abstract available. PMID: 15318472 [PubMed - indexed forMEDLINE]16: Livingstone C, Al Riyami S, Wilkins P, Ferns GA.  McArdle's disease diagnosed following statin-induced myositis. Ann ClinBiochem. 2004 Jul;41(Pt 4):338-40.  PMID: 15298748 [PubMed - in process]17: Chang JT, Staffa JA, Parks M, Green L.  Rhabdomyolysis with HMG-CoA reductase inhibitors and gemfibrozilcombination therapy. Pharmacoepidemiol Drug Saf. 2004 Jul;13(7):417-26.PMID: 15269925 [PubMed - indexed for MEDLINE]18: Carvalho AA, Lima UW, Valiente RA.  Statin and fibrate associated myopathy: 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,Panei. P.  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.  [Worsening for using statin in carnitine palmityol transferase deficiencymyopathy] Rev Neurol. 2004 Jun 1-15;38(11):1095. Spanish. No abstractavailable.  PMID: 15202093 [PubMed - indexed for MEDLINE]21: Takagi A, Shiio Y. [Pravastatin-associated polymyositis, a case report] Rinsho Shinkeigaku.2004 Jan;44(1):25-7. Japanese. PMID: 15199734 [PubMed - indexed for MEDLINE]22: Jamal SM, Eisenberg MJ, Christopoulos S.  Rhabdomyolysis associated with hydroxymethylglutaryl-coenzyme A reductaseinhibitors. Am Heart J. 2004 Jun;147(6):956-65. Review.  PMID: 15199341[PubMed - indexed for MEDLINE]23: Bellosta S, Paoletti R, Corsini A.  Safety of statins: focus on clinical pharmacokinetics and druginteractions. Circulation. 2004 Jun 15;109(23 Suppl 1):III50-7. Review.PMID: 15198967 [PubMed - indexed for MEDLINE]24: Lado Lado FL, Rodriguez Moreno C, Cinza Sajurjo S, Duran Parrondo C,Pazo Nunez M, Lois Pernas A, Masa Vazquez L.  [Statin-induced rhabdomyolysis and renal failure: also with fluvastatine]An Med Interna. 2004 May;21(5):235-7. Spanish. PMID: 15176926 [PubMed -indexed for MEDLINE]25: Guyton JR.  Extended-release niacin for modifying the lipoprotein profile. Expert OpinPharmacother. 2004 Jun;5(6):1385-98. Review.  PMID: 15163282 [PubMed -indexed for MEDLINE] 26: Takagi S. [Neurological complication due to the drug and the maneuver for thetreatment and prevention of cerebrovascular diseases: iatrogenic neurology]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: new hope forolder persons. Am J Geriatr Cardiol. 2004 May-Jun;13(3 Suppl 1):17-24.Review.  PMID: 15133425 [PubMed - indexed for MEDLINE]28: Rando LP, Cording SA, Newnham HH.  Successful reintroduction of statin therapy after myositis: was thereanother cause? Med J Aust. 2004 May 3;180(9):472-3. No abstract available.PMID: 15115429 [PubMed - indexed for MEDLINE]29: Fux R, Morike K, Gundel UF, Hartmann R, Gleiter CH.  Ezetimibe and statin-associated myopathy. Ann Intern Med. 2004 Apr20;140(8):671-2. No abstract available.  PMID: 15096354 [PubMed - indexedfor MEDLINE]30: Roten L, Schoenenberger RA, Krahenbuhl S, Schlienger RG.  Rhabdomyolysis in association with simvastatin and amiodarone. AnnPharmacother. 2004 Jun;38(6):978-81. Epub 2004 Apr 06.  PMID: 15069169[PubMed - indexed for MEDLINE]31: Fauchais AL, Iba Ba J, Maurage P, Kyndt X, Bataille D, Hachulla E,Parent D, Queyrel V, Lambert M, Michon Pasturel U, Hatron PY, Vanhille P,Devulder B. [Polymyositis induced or associated with lipid-lowering drugs: five cases]Rev Med Interne. 2004 Apr;25(4):294-8. French. PMID: 15050796 [PubMed -indexed for MEDLINE]32: Scott LJ, Curran MP, Figgitt DP.  Rosuvastatin: a review of its use in the management of dyslipidemia. Am JCardiovasc Drugs. 2004;4(2):117-38. Review.  PMID: 15049723 [PubMed -indexed for MEDLINE]33: Moosmann B, Behl C.  Selenoprotein synthesis and side-effects of statins. Lancet. 2004 Mar13;363(9412):892-4. Review. PMID: 15031036 [PubMed - indexed for MEDLINE]34:   Sinzinger H, O'Grady J.  Professional athletes suffering from familialhypercholesterolaemia rarelytolerate statin treatment because of muscular problems.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 the prevention and treatment of statin-induced myopathy: isthere a role for ubiquinone 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-induced myopathy. Am J Med. 2004 Mar15;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 ubiquinone concentration and mitochondrial function relativeto cerivastatin-induced skeletal 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 simvastatin and danazol causingrhabdomyolysis. Can J Clin Pharmacol. 2003 Winter;10(4):172-4. PMID:14712320 [PubMed - indexed for MEDLINE]39: Jamil S, Iqbal P.  Rhabdomyolysis induced by a single dose of a statin. Heart. 2004Jan;90(1):e3. PMID: 14676266 [PubMed - indexed for MEDLINE]40: Riesco-Eizaguirre G, Arpa-Gutierrez FJ, Gutierrez M, Toribio E. [Severe polymyositis 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 treatment of mixed hyperlipidemia with acombination of statins and fibrates] Cas Lek Cesk. 2003 Aug;142(8):500-4.Czech. PMID: 14626567 [PubMed - indexed for MEDLINE]42:   Wang TD, Chen WJ, Lin JW, Cheng CC, Chen MF, Lee YT.   Efficacy offenofibrate and simvastatin on endothelial function andinflammatory markers in patients with combined hyperlipidemia: relationswithbaseline lipid profiles.Atherosclerosis. 2003 Oct;170(2):315-23.PMID: 14612213 [PubMed - indexed for MEDLINE]43: Foody JM, Krumholz HM.  Are statins indicated for the primary prevention of CAD in octogenarians?antagonist viewpoint. Am J Geriatr Cardiol. 2003 Nov-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,McKinney. D.  Effectiveness of statin-gemfibrozil combination therapy in patients withmixed hyperlipidemia: experience of a community lipid clinic and safetyreview from the 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 high cholesterol caused bybad genes (familial hypercholesterolemia). Without medication, mycholesterol is above 450 mg/dL. So I am taking high-dose Lipitor (80mg/day), WelChol, and Zetia to lower my cholesterol. I sometimes have painand stiffness in my knees, and my shoulder, elbow, and wrist joints, plusthe muscles in between, are stiff in the morning and hurt during the day.Two years ago I was diagnosed with bursitis in my hips. Could these problemsbe from the Lipitor? If so, is there another statin I could take thatwouldn't do this? Harv Heart Lett. 2003 Oct;14(2):8. No abstract available.PMID: 14576039 [PubMed - indexed for MEDLINE]46: Corsini A.  The safety of HMG-CoA reductase inhibitors in special populations at highcardiovascular risk. Cardiovasc Drugs Ther. 2003 May;17(3):265-85. Review.PMID: 14574085 [PubMed - indexed for MEDLINE]47: Johi RR, Mills R, Halsall PJ, Hopkins PM.  Anaesthetic management of coronary artery bypass grafting in a patientwith central core disease and susceptibility to malignant hyperthermia onstatin therapy. Br J Anaesth. 2003 Nov;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 in 9,416patients.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 with concomitant use of statin andcyclosporin in a 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-associated myopathy. JAMA. 2003 Aug 20;290(7):888; authorreply 888-9. No abstract available.  PMID: 12928463 [PubMed - indexed forMEDLINE]51: Hyman MH.  Issues in statin-associated myopathy. JAMA. 2003 Aug 20;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-lowering drugs and serum liver enzymes: the effects of body weightand baseline enzyme levels. 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 and diabetes. Pravastatin andsimvastatin are the best-assessed statins. Prescrire Int. 2003Aug;12(66):143-8. PMID: 12908497 [PubMed - indexed for MEDLINE]54: Muller T.  [Statin-induced Parkinson's-syndrome. Reader's letter on the article by J.Finsterer in "Der Nervenarzt" (2003) 74:115-122] Nervenarzt. 2003Aug;74(8):726-7. Epub 2003 May 10.  German. No abstract available. PMID:12904874 [PubMed - indexed for MEDLINE]55: Bannwarth B.  Drug-induced myopathies. Expert Opin Drug Saf. 2002 May;1(1):65-70.Review.  PMID: 12904161 [PubMed - indexed for MEDLINE]56:   Davidson MH. Controversy surrounding the safety of cerivastatin.Expert Opin Drug Saf. 2002 Sep;1(3):207-12. Review.  PMID: 12904136[PubMed - indexed for MEDLINE]57: Jacobson TA.  Combination lipid-lowering therapy with statins: safety issues 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 of dyslipidemia: usingniacin-based therapies. Am J Health Syst Pharm. 2003 Jul 1;60(13 Suppl2):S15-21; quiz S25.  PMID: 12901026 [PubMed - indexed for MEDLINE]59: Clotet B, Negredo E.  HIV protease inhibitors and dyslipidemia. AIDS Rev. 2003Jan-Mar;5(1):19-24. Review.  PMID: 12875104 [PubMed - indexed for MEDLINE]60: Arenas J, Martin MA. [Metabolic intolerance to exercise] 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 of statins] 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 coronary heart disease patients with low HDL:which options do we have? Int J Cardiol. 2003 Jul;90(1):15-21. Review. PMID:12821213 [PubMed - indexed for MEDLINE]63: Teichholz LE.  Statin-associated myopathy with normal creatine kinase levels. Ann InternMed. 2003 Jun 17;138(12):1008; author reply 1008-9. No abstract available.PMID: 12809468 [PubMed - indexed for MEDLINE]64: Torgovnick J, Arsura E.  Statin-associated myopathy with normal creatine kinase levels. Ann InternMed. 2003 Jun 17;138(12):1007; author reply 1008-9. No abstract available.PMID: 12809467 [PubMed - indexed for MEDLINE]65: Hyman MH.  Statin-associated myopathy with normal creatine kinase levels. Ann InternMed. 2003 Jun 17;138(12):1007; author reply 1008-9. No abstract available.PMID: 12809466 [PubMed - indexed for MEDLINE]66: Toma E, Loignon M.  Statin-associated myopathy with normal creatine kinase levels. Ann InternMed. 2003 Jun 17;138(12):1007-8; author reply 1008-9. No abstract available.PMID: 12809465 [PubMed - indexed for MEDLINE]67: Ornato JP.  Should you worry about the side effects of statins? Statin dose, health,and other drugs affect side-effect risk. Health News. 2003 Jun;9(6):1-2. Noabstract available.  PMID: 12793395 [PubMed - indexed for MEDLINE]68: Davidson MH.  Combination lipid-lowering therapy in diabetes. Curr Diab Rep. 2003Jun;3(3):263-8. Review. PMID: 12762976 [PubMed - indexed for MEDLINE]69: Schmitz G, Drobnik W.  Pharmacogenomics and pharmacogenetics of cholesterol-lowering therapy.Clin Chem Lab Med. 2003 Apr;41(4):581-9. Review.  PMID: 12747606 [PubMed -indexed for MEDLINE]70: Worz CR, Bottorff M.  Treating dyslipidemic patients with lipid-modifying and combinationtherapies. Pharmacotherapy. 2003 May;23(5):625-37. Review.  PMID: 12741437[PubMed - indexed for MEDLINE]71: Bays H, Dujovne C.  Colesevelam HCl: a non-systemic lipid-altering drug. Expert OpinPharmacother. 2003 May;4(5):779-90. Review.  PMID: 12740000 [PubMed -indexed for MEDLINE]72: Paragh G, Balogh Z, Romics L.  [Antilipemic therapy and rhabdomyolysis] Orv Hetil. 2003 Mar16;144(11):515-20. Review.  Hungarian.  PMID: 12731338 [PubMed - indexed forMEDLINE]73: Gotto AM Jr.  Risks and benefits of continued aggressive statin therapy. Clin Cardiol.2003 Apr;26(4 Suppl 3):III3-12. Review. PMID: 12708633 [PubMed - indexed forMEDLINE]74: Thompson PD, Clarkson P, Karas RH.  Statin-associated myopathy. JAMA. 2003 Apr 2;289(13):1681-90. Review.PMID: 12672737 [PubMed - indexed for MEDLINE]75: Braun RN, Halhuber MJ, Hitzenberger G.  [Information regarding adverse drug effects and treatment indications("package inserts") exemplified by cervistatin (Lipobay)] Wien MedWochenschr. 2003;153(3-4):80-2.  German.  PMID: 12658968 [PubMed - indexedfor MEDLINE]76: Lee TH.  Ask the doctor. At age 62 I'm a bit overweight and have diabetes. I take astatin, and my LDL cholesterol is good (84 mg/dL). But my HDL is low (30mg/dL) and my triglycerides are above 300 mg/dL. Are high triglycerides aproblem? Harv Heart Lett. 2003 Mar;13(7):8. No abstract available.  PMID:12654588 [PubMed - indexed for MEDLINE]77: [No authors listed]  How a statin might destroy a drug company. Lancet. 2003 Mar8;361(9360):793. No abstract available.  PMID: 12642039 [PubMed - indexedfor MEDLINE]78: Smith CC, Bernstein LI, Davis RB, Rind DM, Shmerling RH.  Screening for statin-related toxicity: the yield of transaminase andcreatine kinase measurements in a primary care setting. Arch Intern Med.2003 Mar 24;163(6):688-92. PMID: 12639201 [PubMed - indexed for MEDLINE]79: Gotto AM Jr.  Safety and statin therapy: reconsidering the risks and benefits. ArchIntern Med. 2003 Mar 24;163(6):657-9. No abstract available.  PMID: 12639194[PubMed - indexed for MEDLINE]80: Ballantyne CM, Corsini A, Davidson MH, Holdaas H, Jacobson TA,Leitersdorf E, Marz W, Reckless JP, Stein EA.  Risk for myopathy with statin therapy in high-risk patients. Arch InternMed. 2003 Mar 10;163(5):553-64. Review.  PMID: 12622602 [PubMed - indexedfor MEDLINE]81:   Bennett WE, Drake AJ 3rd, Shakir KM.   Reversible myopathy afterstatin therapy in patients with normal creatinekinase levels.Ann Intern Med. 2003 Mar 4;138(5):436-7. No abstract available.PMID: 12614104 [PubMed - indexed for MEDLINE]82: Farmer JA. Statins and myotoxicity. Curr Atheroscler Rep. 2003 Mar;5(2):96-100.Review. PMID: 12573193 [PubMed - indexed for MEDLINE]83: Glueck CJ, Streicher P.  Cardiovascular and medical ramifications of treatment of subclinicalhypothyroidism. Curr Atheroscler Rep. 2003 Jan;5(1):73-7. Review. PMID:12562546 [PubMed - indexed for MEDLINE]84: Sinzinger H.  Statin-induced myositis migrans. Wien Klin Wochenschr. 2002 Nov30;114(21-22):943-4.  PMID: 12528328 [PubMed - indexed for MEDLINE]85: Yim BT, Chong PH.  Niacin-ER and lovastatin treatment of hypercholesterolemia and mixeddyslipidemia. Ann Pharmacother. 2003 Jan;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, Sobh M,Amer G.  Neuromuscular toxicity in nephrotic patients treated with fluvastatin. JNephrol. 2002 Nov-Dec;15(6):690-5. PMID: 12495286 [PubMed - indexed forMEDLINE]87: Black C, Jick H.  Etiology and frequency of rhabdomyolysis. Pharmacotherapy. 2002Dec;22(12):1524-6.  PMID: 12495162 [PubMed - indexed for MEDLINE]88: Xydakis AM, Ballantyne CM.  Combination therapy for combined dyslipidemia. Am J Cardiol. 2002 Nov20;90(10B):21K-29K. Review.  PMID: 12467937 [PubMed - indexed for MEDLINE]89: Mantel-Teeuwisse AK, Klungel OH, Herings RM, van Puijenbroek EP, PorsiusAJ, de Boer A.  Myopathy due to statin/fibrate use in the Netherlands. Ann Pharmacother.2002 Dec;36(12):1957-60.PMID: 12452761 [PubMed - indexed for MEDLINE]90: Bolego C, Baetta R, Bellosta S, Corsini A, Paoletti R.  Safety considerations 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 red yeast rice (Monascus purpureus) in a renaltransplant recipient. 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 of a statin and gemfibrozil: anuncommon but serious adverse reaction. WMJ. 2002;101(7):53-6. PMID: 12426921[PubMed - indexed for MEDLINE]93: Schuff-Werner P, Kohlschein P.  [Current therapy of hypercholesterolemia. How much statin does yourpatient need?] MMW Fortschr Med. 2002 Aug 8;144(31-32):24-6.  German.  PMID:12422725 [PubMed - indexed for MEDLINE]94: Hare CB, Vu MP, Grunfeld C, Lampiris HW.  Simvastatin-nelfinavir interaction implicated in rhabdomyolysis and death.Clin Infect Dis. 2002 Nov 15;35(10):e111-2. Epub 2002 Oct 25.  PMID:12410494 [PubMed - indexed for MEDLINE]95: Phillips PS, Haas RH, Bannykh S, Hathaway S, Gray NL, Kimura BJ,Vladutiu GD, England JD; Scripps Mercy Clinical Research Center.  Statin-associated myopathy with normal creatine kinase 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 concurrent atorvastatin and diltiazem. AnnPharmacother. 2002 Oct;36(10):1546-9.  PMID: 12243603 [PubMed - indexed forMEDLINE]97: Sinzinger H, Chehne F, Lupattelli G.  Oxidation injury in patients receiving HMG-CoA reductase inhibitors:occurrence in patients without enzyme elevation or myopathy. Drug Saf.2002;25(12):877-83.  PMID: 12241128 [PubMed - indexed for MEDLINE] 98:Aboulafia DM, Johnston R.  Simvastatin-induced rhabdomyolysis in an HIV-infected patient withcoronary artery disease. AIDS Patient Care STDS. 2000 Jan;14(1):13-8. PMID:12240878 [PubMed - indexed for MEDLINE]99: Vivekananthan K, Mehra MR, Uber PA, DeGruiter H, Lavie CJ, Milani RV.  Comparison of the efficacy and safety of pravastatin and simvastatin inheart transplantation. J Assoc Physicians India. 2002 May;50(5):682-4. PMID:12186124 [PubMed - indexed for MEDLINE]100: Evans M, Rees A.  Effects of HMG-CoA reductase inhibitors on skeletal muscle: are allstatins the same? Drug Saf. 2002;25(9):649-63. Review.  PMID: 12137559[PubMed - indexed for MEDLINE]101: Sinzinger H, Wolfram R, Peskar BA. Muscular side effects of statins. J Cardiovasc Pharmacol. 2002Aug;40(2):163-71. Review.  PMID: 12131545 [PubMed - indexed for MEDLINE]102: Heart Protection Study Collaborative Group.  MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet.2002 Jul 6;360(9326):7-22. Summary for patients in: Curr Cardiol Rep. 2002Nov;4(6):486-7. PMID: 12114036 [PubMed - indexed for MEDLINE]103: Bae J, Jarcho JA, Denton MD, Magee CC.  Statin specific toxicity in organ transplant recipients: case report andreview of the literature. J Nephrol. 2002 May-Jun;15(3):317-9. Review. PMID:12113605 [PubMed - indexed for MEDLINE]104: de Sauvage Nolting PR, Buirma RJ, Hutten BA, Kastelein JJ; DutchExPRESS Investigator Group.  Two-year efficacy and safety of simvastatin 80 mg in familialhypercholesterolemia (the Examination of Probands and Relatives in StatinStudies With Familial Hypercholesterolemia [ExPRESS FH]). Am J Cardiol. 2002Jul 15;90(2):181-4. No abstract available.  PMID: 12106856 [PubMed - indexedfor MEDLINE]105: Liamis G, Kakafika A, Bairaktari E, Miltiadous G, Tsimihodimos V,Goudevenos J, Achimastos A, Elisaf M.  Combined treatment with fibrates and small doses of atorvastatin inpatients with mixed hyperlipidemia. Curr Med Res Opin. 2002;18(3):125-8.PMID: 12094821 [PubMed - indexed for MEDLINE]106: Williams D, Feely J.  Pharmacokinetic-pharmacodynamic drug interactions with HMG-CoA reductaseinhibitors. Clin Pharmacokinet. 2002;41(5):343-70. Review.  PMID: 12036392[PubMed - indexed for MEDLINE]107: Sinzinger H. Flu-like response on statins. Med Sci Monit. 2002 May;8(5):CR384-8. PMID:12011782 [PubMed - indexed for MEDLINE]108: [No authors listed]  Statin stories. Diabetes Obes Metab. 2002 Mar;4(2):138. No abstractavailable.  PMID: 11993442 [PubMed - indexed for MEDLINE]109: Maxa JL, Melton LB, Ogu CC, Sills MN, Limanni A.  Rhabdomyolysis after concomitant use of cyclosporine, simvastatin,gemfibrozil, and itraconazole. Ann Pharmacother. 2002 May;36(5):820-3.PMID: 11978159 [PubMed - indexed for MEDLINE]110: Foxton J. Statin safety. Nurs Stand. 2001 Sep 19-25;16(1):20. No abstract available.PMID: 11977679 [PubMed - indexed for MEDLINE]111: Gensini GF, Conti AA, Conti A, Panti A.  [From prevention to cardiovascular rehabilitation: statins andevidence-based medicine] Ital Heart J Suppl. 2002 Jan;3(1):91-4. Review.Italian. PMID: 11899580 [PubMed - indexed for MEDLINE]112: Sica DA, Gehr TW.  3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors andrhabdomyolysis: considerations in the renal failure patient. Curr OpinNephrol Hypertens. 2002 Mar;11(2):123-33. Review.  PMID: 11856903 [PubMed -indexed for MEDLINE]113: Omar MA, Wilson JP.  FDA adverse event reports on statin-associated rhabdomyolysis. AnnPharmacother. 2002 Feb;36(2):288-95. Review.  PMID: 11847951 [PubMed -indexed for MEDLINE]114: Prieto JC. [Safety profile of statins] Rev Med Chil. 2001 Nov;129(11):1237-40.Spanish. PMID: 11836874 [PubMed - indexed for MEDLINE]115: Sica DA, Gehr TW.  Rhabdomyolysis and statin therapy: relevance to the elderly. Am J GeriatrCardiol. 2002 Jan-Feb;11(1):48-55. Review.  PMID: 11773716 [PubMed - indexedfor MEDLINE]116: Banga JD.  [Myotoxicity and rhabdomyolisis due to statins] Ned Tijdschr Geneeskd.2001 Dec 8;145(49):2371-6. Review.  Dutch. PMID: 11770264 [PubMed - indexedfor MEDLINE]117: Hamilton-Craig I.  Statin-associated myopathy. Med J Aust. 2001 Nov 5;175(9):486-9. Review.PMID: 11758079 [PubMed - indexed for MEDLINE]118: Bernini F, Poli A, Paoletti R.  Safety of HMG-CoA reductase inhibitors: focus on atorvastatin. CardiovascDrugs Ther. 2001;15(3):211-8. Review.  PMID: 11713888 [PubMed - indexed forMEDLINE]119: Chazerain P, Hayem G, Hamza S, Best C, Ziza JM.  Four cases of tendinopathy in patients on statin therapy. Joint BoneSpine. 2001 Oct;68(5):430-3.  PMID: 11707010 [PubMed - indexed for MEDLINE]120: Federman DG, Hussain F, Walters AB.  Fatal rhabdomyolysis caused by lipid-lowering therapy. South Med J. 2001Oct;94(10):1023-6. PMID: 11702815 [PubMed - indexed for MEDLINE]121: Baker SK, Tarnopolsky MA.  Statin myopathies: pathophysiologic and clinical perspectives. Clin InvestMed. 2001 Oct;24(5):258-72. Review. No abstract available.  PMID: 11603510[PubMed - indexed for MEDLINE]122: Igel M, Sudhop T, von Bergmann K.   Metabolism and drug interactions of3-hydroxy-3-methylglutaryl coenzymeA-reductase inhibitors (statins).Eur J Clin Pharmacol. 2001 Aug;57(5):357-64. Review.PMID: 11599653 [PubMed - indexed for MEDLINE]123: Tomlinson B, Chan P, Lan W.  How well tolerated are lipid-lowering drugs?Drugs Aging. 2001;18(9):665-83. Review.PMID: 11599634 [PubMed - indexed for MEDLINE]124: Bangratz S.  [Complications in heart transplantation: diagnosis and treatment]Presse Med. 2001 Sep 1;30(24 Pt 2):8-12. Review.  French.PMID: 11577591 [PubMed - indexed for MEDLINE]125: Omar MA, Wilson JP, Cox TS.  Rhabdomyolysis and HMG-CoA reductase inhibitors.Ann Pharmacother. 2001 Sep;35(9):1096-107. Review. Erratum in: AnnPharmacother2001 Oct;35(10):1296.PMID: 11573861 [PubMed - indexed for MEDLINE]126: Boger RH.  Drug interactions of the statins and consequences for drug selection.Int J Clin Pharmacol Ther. 2001 Sep;39(9):369-82. Review.PMID: 11563683 [PubMed - indexed for MEDLINE]127: Comarow A.  Rest easy, statin users. Benefits dwarf risks for these cholesterol drugs.US News World Rep. 2001 Sep 3;131(8):45. No abstract available.PMID: 11550394 [PubMed - indexed for MEDLINE]128: Shek A, Ferrill MJ.  Statin-fibrate combination therapy.Ann Pharmacother. 2001 Jul-Aug;35(7-8):908-17. Review.PMID: 11485144 [PubMed - indexed for MEDLINE]129: Lupattelli G, Palumbo B, Sinzinger H.  Statin induced myopathy does not show up in MIBI scintigraphy.Nucl Med Commun. 2001 May;22(5):575-8.PMID: 11388581 [PubMed - indexed for MEDLINE]130: 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]131: Moghadasian MH, Mancini GB, Frohlich JJ.  Pharmacotherapy of hypercholesterolaemia: statins in clinical practice.Expert Opin Pharmacother. 2000 May;1(4):683-95. Review.  PMID: 11249510[PubMed - indexed for MEDLINE]132: Oldemeyer JB, Lund RJ, Koch M, Meares AJ, Dunlay R.  Rhabdomyolysis and acute renal failure after changing statin-fibratecombinations. Cardiology. 2000;94(2):127-8. PMID: 11173785 [PubMed - indexedfor MEDLINE]133: Sinzinger H, Lupattelli G, Chehne F.  Increased lipid peroxidation in a patient with CK-elevation and musclepain during statin therapy. Atherosclerosis. 2000 Nov;153(1):255-6. Noabstract available. PMID: 11058722 [PubMed - indexed for MEDLINE]134: Guyton JR.  Combination drug therapy for combined hyperlipidemia. Curr Cardiol Rep.1999 Sep;1(3):244-50. Review. PMID: 10980849 [PubMed - indexed for MEDLINE]135: Ozdemir O, Boran M, Gokce V, Uzun Y, Kocak B, Korkmaz S.  A case with severe rhabdomyolysis and renal failure associated withcerivastatin-gemfibrozil combination therapy--a case report. Angiology. 2000Aug;51(8):695-7. PMID: 10959522 [PubMed - indexed for MEDLINE]136: Gavish D, Leibovitz E, Shapira I, Rubinstein A.  Bezafibrate and simvastatin combination therapy for diabeticdyslipidaemia: efficacy and safety. J Intern Med. 2000 May;247(5):563-9.PMID: 10809995 [PubMed - indexed for MEDLINE]137: Liebhaber MI, Wright RS, Gelberg HJ, Dyer Z, Kupperman JL.  Polymyalgia, hypersensitivity pneumonitis and other reactions in patientsreceiving HMG-CoA reductase inhibitors: a report of ten cases. Chest. 1999Mar;115(3):886-9. PMID: 10084510 [PubMed - indexed for MEDLINE]138: Guyton JR, Capuzzi DM.  Treatment of hyperlipidemia with combined niacin-statin regimens. Am JCardiol. 1998 Dec 17;82(12A):82U-84U;  discussion 85-86U. Review. PMID:9915667 [PubMed - indexed for MEDLINE]139: Athyros VG, Papageorgiou AA, Hatzikonstandinou HA, Didangelos TP,Carina MV, Kranitsas DF, Kontopoulos AG.  Safety and efficacy of long-term statin-fibrate combinations in patientswith refractory familial combined hyperlipidemia. Am J Cardiol. 1997 Sep1;80(5):608-13.  PMID: 9294990 [PubMed - indexed for MEDLINE]140: Tikkanen MJ.  Statins: within-group comparisons, statin escape and combination therapy.Curr Opin Lipidol. 1996 Dec;7(6):385-8. Review. PMID: 9117143 [PubMed -indexed for MEDLINE]141: 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-CoAreductase inhibitors on serum ubiquinone and blood lactate/pyruvate ratio.Br J Clin Pharmacol. 1996 Sep;42(3):333-7.  PMID: 8877024 [PubMed - indexedfor MEDLINE]142: Reijneveld JC, Koot RW, Bredman JJ, Joles JA, Bar PR.  Differential effects of 3-hydroxy-3-methylglutaryl-coenzyme A reductaseinhibitors on the development of myopathy in young rats. Pediatr Res. 1996Jun;39(6):1028-35. PMID: 8725265 [PubMed - indexed for MEDLINE]143: Peters TK. Safety profile of fluvastatin. Br J Clin Pract Suppl. 1996 Jan;77A:20-3.Review. PMID: 8729586 [PubMed - indexed for MEDLINE]144: Laaksonen R, Jokelainen K, Sahi T, Tikkanen MJ, Himberg JJ.  Decreases in serum ubiquinone concentrations do not result in reducedlevels in muscle tissue during short-term simvastatin treatment in humans.Clin Pharmacol Ther. 1995 Jan;57(1):62-6.  PMID: 7828383 [PubMed - indexedfor MEDLINE]145: Leitersdorf E, Muratti EN, Eliav O, Meiner V, Eisenberg S, Dann EJ,Sehayek E, Peters TK, Stein Y.  Efficacy and safety of a combination fluvastatin-bezafibrate treatment forfamilial hypercholesterolemia: comparative analysis with afluvastatin-cholestyramine combination. Am J Med. 1994 May;96(5):401-7.PMID: 8192170 [PubMed - indexed for MEDLINE]146: Dromer C, Vedrenne C, Billey T, Pages M, Fournie B, Fournie A.[Rhabdomyolysis due to simvastin. Apropos of a case with review of theliterature] Rev Rhum Mal Osteoartic. 1992 Apr;59(4):281-3. Review.  French.PMID: 1496277 [PubMed - indexed for MEDLINE]Search terms: STATIN + MYOSITIS1: [No authors listed] Safety of aggressive statin therapy. Med Lett Drugs Ther. 2004 Nov22;46(1196):93-5. PMID: 15557874 [PubMed - indexed for MEDLINE]2: Sniderman AD.  Is there value in liver function test and creatine phosphokinasemonitoring with statin use? Am J Cardiol. 2004 Nov 4;94(9A):30F-34F. Review.PMID: 15519289 [PubMed - indexed for MEDLINE]3: Phillips PS, Phillips CT, Sullivan MJ, Naviaux RK, Haas RH.  Statin myotoxicity is associated with changes in the cardiopulmonaryfunction. Atherosclerosis. 2004 Nov;177(1):183-8. PMID: 15488882 [PubMed -in process]Phillips CT, Gray NL, Puhek LM et al. (2004), Basal respiratory exchangeratio is altered with statin use in normals. J Am Cardio 43(suppl A):233a.4: Livingstone C, Al Riyami S, Wilkins P, Ferns GA.  McArdle's disease diagnosed following statin-induced myositis. Ann ClinBiochem. 2004 Jul;41(Pt 4):338-40.  PMID: 15298748 [PubMed - in process]5: Takagi A, Shiio Y. [Pravastatin-associated polymyositis, a case report] Rinsho Shinkeigaku.2004 Jan;44(1):25-7. Japanese. PMID: 15199734 [PubMed - indexed for MEDLINE]6: Bellosta S, Paoletti R, Corsini A.  Safety of statins: focus on clinical pharmacokinetics and druginteractions. Circulation. 2004 Jun 15;109(23 Suppl 1):III50-7. Review.PMID: 15198967 [PubMed - indexed for MEDLINE]7: Rando LP, Cording SA, Newnham HH.  Successful reintroduction of statin therapy after myositis: was thereanother cause? Med J Aust. 2004 May 3;180(9):472-3. No abstract available.PMID: 15115429 [PubMed - indexed for MEDLINE] 8: Fauchais AL, Iba Ba J,Maurage P, Kyndt X, Bataille D, Hachulla E, Parent D, Queyrel V, Lambert M,Michon Pasturel U, Hatron PY, Vanhille P, Devulder B. [Polymyositis induced or associated with lipid-lowering drugs: five cases]Rev Med Interne. 2004 Apr;25(4):294-8. French. PMID: 15050796 [PubMed -indexed for MEDLINE]9: Riesco-Eizaguirre G, Arpa-Gutierrez FJ, Gutierrez M, Toribio E. [Severe polymyositis with simvastatin use] Rev Neurol. 2003 Nov16-30;37(10):934-6. Spanish. PMID: 14634922 [PubMed - indexed for MEDLINE]10: Foody JM, Krumholz HM.  Are statins indicated for the primary prevention of CAD in octogenarians?antagonist viewpoint. Am J Geriatr Cardiol. 2003 Nov-Dec;12(6):357-60.Review.  PMID: 14610384 [PubMed - indexed for MEDLINE]. 11: Shammas NW, Kapalis MJ, Deckert J, Harris M, Dippel EJ, Labroo A,McKinney. D.  Effectiveness of statin-gemfibrozil combination therapy in patients withmixed hyperlipidemia: experience of a community lipid clinic and safetyreview from the literature. Prev Cardiol. 2003 Fall;6(4):189-94.  PMID:14605512 [PubMed - indexed for MEDLINE]12: Badawy O, Wierzbicki AS, Hilton R.  Combination fibrate-statin therapy for the treatment of severehypertriglyceridaemia in renal disease. Int J Clin Pract. 2003Apr;57(3):249-51.  PMID: 12723736 [PubMed - indexed for MEDLINE]13: Thompson PD, Clarkson P, Karas RH.  Statin-associated myopathy. JAMA. 2003 Apr 2;289(13):1681-90. Review.PMID: 12672737 [PubMed - indexed for MEDLINE]14: Sinzinger H.  Statin-induced myositis migrans. Wien Klin Wochenschr. 2002 Nov30;114(21-22):943-4.  PMID: 12528328 [PubMed - indexed for MEDLINE]15: Black C, Jick H.  Etiology and frequency of rhabdomyolysis. Pharmacotherapy. 2002Dec;22(12):1524-6.  PMID: 12495162 [PubMed - indexed for MEDLINE] 16:Lawrence JM, Reckless JP. Fluvastatin. Expert Opin Pharmacother. 2002 Nov;3(11):1631-41. Review.PMID: 12437496 [PubMed - indexed for MEDLINE]17: Mehra MR, Uber PA, Vivekananthan K, Solis S, Scott RL, Park MH, MilaniRV, Lavie CJ.  Comparative beneficial effects of simvastatin and pravastatin on cardiacallograft rejection and survival. J Am Coll Cardiol. 2002 Nov6;40(9):1609-14.  PMID: 12427413 [PubMed - indexed for MEDLINE]18: Evans M, Rees A.  Effects of HMG-CoA reductase inhibitors on skeletal muscle: are allstatins the same? Drug Saf. 2002;25(9):649-63. Review.  PMID: 12137559[PubMed - indexed for MEDLINE]19: Aronow WS.  Pharmacologic therapy of lipid disorders in the elderly. Am J GeriatrCardiol. 2002 Jul-Aug;11(4):247-56. Review.  PMID: 12091773 [PubMed -indexed for MEDLINE]20: Patel DN, Pagani FD, Koelling TM, Dyke DB, Baliga RR, Cody RJ, Lake KD,Aaronson KD.  Safety and efficacy of atorvastatin in heart transplant recipients. JHeart Lung Transplant. 2002 Feb;21(2):204-10. PMID: 11834348 [PubMed -indexed for MEDLINE]Search terms: STATIN + MYALGIA1: Koller H, Neuhaus O, Schroeter M, Hartung HP. [Myopathies under therapy with lipid-lowering agents.] Nervenarzt. 2004 Dec18; [Epub ahead of print] German.  PMID: 15609055 [PubMed - as supplied bypublisher]2: Rundek T, Naini A, Sacco R, Coates K, DiMauro S.  Atorvastatin decreases the coenzyme Q10 level in the blood of patients atrisk for cardiovascular disease and stroke. Arch Neurol. 2004Jun;61(6):889-92. PMID: 15210526 [PubMed - indexed for MEDLINE]3: Takagi A, Shiio Y. [Pravastatin-associated polymyositis, a case report] Rinsho Shinkeigaku.2004 Jan;44(1):25-7. Japanese. PMID: 15199734 [PubMed - indexed for MEDLINE]4: Scott LJ, Curran MP, Figgitt DP.  Rosuvastatin: a review of its use in the management of dyslipidemia. Am JCardiovasc Drugs. 2004;4(2):117-38. Review.  PMID: 15049723 [PubMed -indexed for MEDLINE]5: Newman CB, Palmer G, Silbershatz H, Szarek M.  Safety of atorvastatin derived from analysis of 44 completed trials in9,416 patients. Am J Cardiol. 2003 Sep 15;92(6):670-6.  PMID: 12972104[PubMed - indexed for MEDLINE]6: Andrejak M, Gras V, Massy ZA, Caron J. [Adverse effects of statins] Therapie. 2003 Jan-Feb;58(1):77-83. Review.French. PMID: 12822204 [PubMed - indexed for MEDLINE]7: Thompson PD, Clarkson P, Karas RH.  Statin-associated myopathy. JAMA. 2003 Apr 2;289(13):1681-90. Review.PMID: 12672737 [PubMed - indexed for MEDLINE]8: Athyros VG, Papageorgiou AA, Athyrou VV, Demitriadis DS, Pehlivanidis AN,Kontopoulos AG.  Atorvastatin versus four statin-fibrate combinations in patients withfamilial combined hyperlipidaemia. J Cardiovasc Risk. 2002 Feb;9(1):33-9.PMID: 11984215 [PubMed - indexed for MEDLINE]9: Taher TH, Dzavik V, Reteff EM, Pearson GJ, Woloschuk BL, Francis GA.  Tolerability of statin-fibrate and statin-niacin combination therapy indyslipidemic patients at high risk for cardiovascular events. Am J Cardiol.2002 Feb 15;89(4):390-4.  PMID: 11835917 [PubMed - indexed for MEDLINE]10: Chazerain P, Hayem G, Hamza S, Best C, Ziza JM.  Four cases of tendinopathy in patients on statin therapy. Joint BoneSpine. 2001 Oct;68(5):430-3.  PMID: 11707010 [PubMed - indexed for MEDLINE]11: Penzak SR, Chuck SK, Stajich GV.  Safety and efficacy of HMG-CoA reductase inhibitors for treatment ofhyperlipidemia in patients with HIV infection. Pharmacotherapy. 2000Sep;20(9):1066-71.  PMID: 10999499 [PubMed - indexed for MEDLINE] 12:Spieker LE, Noll G, Hannak M, Luscher TF.  Efficacy and tolerability of fluvastatin and bezafibrate in patients withhyperlipidemia and persistently high triglyceride levels. J CardiovascPharmacol. 2000 Mar;35(3):361-5. PMID: 10710119 [PubMed - indexed forMEDLINE]13: Papadakis JA, Ganotakis ES, Jagroop IA, Winder AF, Mikhailidis DP.  Statin + fibrate combination therapy fluvastatin with bezafibrate orciprofibrate in high risk patients with vascular disease. Int J Cardiol.1999 Jun 1;69(3):237-44. PMID: 10402106 [PubMed - indexed for MEDLINE]14: Peters TK. Safety profile of fluvastatin. Br J Clin Pract Suppl. 1996 Jan;77A:20-3.Review. PMID: 8729586 [PubMed - indexed for MEDLINE]Search terms: STATIN + POLYMYOSITIS1: Takagi A, Shiio Y. [Pravastatin-associated polymyositis, a case report] Rinsho Shinkeigaku.2004 Jan;44(1):25-7. Japanese. PMID: 15199734 [PubMed - indexed for MEDLINE]2: Bellosta S, Paoletti R, Corsini A.  Safety of statins: focus on clinical pharmacokinetics and druginteractions. Circulation. 2004 Jun 15;109(23 Suppl 1):III50-7. Review.PMID: 15198967 [PubMed - indexed for MEDLINE]3: 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, DevulderB. [Polymyositis induced or associated with lipid-lowering drugs: five cases]Rev Med Interne. 2004 Apr;25(4):294-8. French. PMID: 15050796 [PubMed -indexed for MEDLINE]4: Riesco-Eizaguirre G, Arpa-Gutierrez FJ, Gutierrez M, Toribio E. [Severe polymyositis with simvastatin use] Rev Neurol. 2003 Nov16-30;37(10):934-6. Spanish. PMID: 14634922 [PubMed - indexed for MEDLINE]5: Bannwarth B.  Drug-induced myopathies. Expert Opin Drug Saf. 2002 May;1(1):65-70.Review.  PMID: 12904161 [PubMed - indexed for MEDLINE] 6: Chazerain P, HayemG, Hamza S, Best C, Ziza JM.  Four cases of tendinopathy in patients on statin therapy. Joint BoneSpine. 2001 Oct;68(5):430-3.  PMID: 11707010 [PubMed - indexed for MEDLINE]Arduini A, Peschechera A, Giannessi F, Carminati P.  Improvement of statin-associated myotoxicity by L-carnitine. J ThrombHaemost. 2004 Dec;2(12):2270-1. No abstract available.  PMID: 15613049[PubMed - in process]RHABDOMYOLYSIS AND STATINSFrequently Asked Question: What is Rhabdomyolysis?According to the medical dictionary on Medicinenet.comhttp://www.medterms.com/script/main/art.asp?articlekey=5352"Source: http://www.medterms.com MedTerms is the Medical Dictionary ofMedicineNet.comRhabdomyolysis: A condition in which skeletal muscle cells break down,releasing myoglobin (the oxygen-carrying pigment in muscle) together withenzymes and electrolytes from inside the muscle cells. The risks withrhabdomyolysis include muscle breakdown and kidney failure since myoglobinis toxic to the kidneys.Rhabdomyolysis can occur from extensive muscle damage as, for example, froma crushing injury or an electrical shock. Drugs or toxins, particularly someof the cholesterol lowering medications such as cerivastatin (Baycol), maycause this disorder. Underlying diseases such as systemic lupuserythematosus can also lead to rhabdomyolysis. It is a common complicationof major burns.The key signs and symptoms of rhabdomyolysis include dark, red, or colacolored urine and muscle tenderness, stiffness, aching (myalgia) orweakness. Laboratory confirmation can come from the demonstration ofmyoglobin in the blood or urine.Ideal treatment involves early and aggressive hydration with very largeamounts of IV fluids to flush the myoglobin out of the kidneys. Diureticsmay help. So may bicarbonate which makes the urine alkaline to prevent thebreakdown of myoglobin into more toxic compounds.From the Greek roots rhabdo-, striped (striated) + -myo-, muscle + -lysis,breakdown = the breakdown of striated muscle (skeletal muscle).Last Editorial Review: 3/14/03 ? 1996-2005 MedicineNet, Inc. All rightsreserved. Copyright and Legal Disclaimer.  Information on this web site isprovided for informational purposes only and is not a substitute forprofessional medical advice. You should not use the information on this website for diagnosing or treating a medical or health condition. You shouldcarefully read all product packaging. If you have or suspect you have amedical problem, promptly contact your professional healthcare provider.Statements and information regarding dietary supplements have not beenevaluated or approved by the Food and Drug Administration. Please consultyour healthcare provider before beginning any course of supplementation ortreatment."See the ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of Statins,search on "rhabdomyolysis."http://www.nhlbi.nih.gov/guidelines/cholesterol/statins.pdfFrequently Asked Question: Which statins cause deadly Rhabdomyolysis?All of them.For more, see :FDA adverse event reports on statin-associated rhabdomyolysis.Omar MA, Wilson JP.Ann Pharmacother. 2002 Feb;36(2):288-95. Review.PMID: 11847951http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11847951
&dopt=AbstractOf 871 reports detailing 601 cases in a 29 month time frame, the list ofstatin, number ofcases, and percentage of the whole follows:simvastatin, 215 (35.8%);cerivastatin, 192 (31.9%);atorvastatin, 73 (12.2%);pravastatin, 71 (11.8%);lovastatin, 40 (6.7%);fluvastatin, 10 (1.7%)As of August, 2001, there were at least 81rhabdomyolysis deaths associatedwith Non-Baycol statins.http://www.essentialdrugs.org/edrug/archive/200108/msg00064.phpThe Public Citizen petition to the FDA, August 20,2001:http://www.citizen.org/publications/release.cfm?ID=7051At that time the count of deaths by statin-induced rhabdomyolysis:OutcomeNumber of CasesPercent of Total DeathsDeathsAtorvastatin1318.1%Cerivastatin2027.8%Fluvastatin11.4%Lovastatin56.9%Pravastatin912.5%Simvastatin2433.3%1: Jones PH, Davidson MH.  Reporting rate of rhabdomyolysis with fenofibrate + statin versusgemfibrozil + any statin. Am J Cardiol. 2005 Jan 1;95(1):120-2.  PMID:15619408 [PubMed - in process]2: Koller H, Neuhaus O, Schroeter M, Hartung HP. [Myopathies under therapy with lipid-lowering agents.] Nervenarzt. 2004 Dec18; [Epub ahead of print] German.  PMID: 15609055 [PubMed - as supplied bypublisher]3: De Angelis G.  The influence of statin characteristics on their safety and tolerability.Int J Clin Pract. 2004 Oct;58(10):945-55.  PMID: 15587774 [PubMed - inprocess]4: Ducobu J, Sternon J. [Ezetimibe (Ezetrol): the statins' partner] Rev Med Brux. 2004Oct;25(5):456-61. French. PMID: 15584647 [PubMed - in process]5: [No authors listed] A warning about one statin at a high dose. Heart Advis. 2004 Nov;7(11):2.No abstract available.  PMID: 15580669 [PubMed - indexed for MEDLINE]6: Graham DJ, Staffa JA, Shatin D, Andrade SE, Schech SD, La Grenade L,Gurwitz JH, Chan KA, Goodman MJ, Platt R.  Incidence of hospitalized rhabdomyolysis in patients treated withlipid-lowering drugs. JAMA. 2004 Dec 1;292(21):2585-90. Epub 2004 Dec 1.PMID: 15572716 [PubMed - indexed for MEDLINE]7: [No authors listed] Safety of aggressive statin therapy. Med Lett Drugs Ther. 2004 Nov22;46(1196):93-5. PMID: 15557874 [PubMed - indexed for MEDLINE]8: [No authors listed]  Rosuvastatin: new preparation. Opt for statins with evidence of efficacyon clinical outcome. Prescrire Int. 2004 Aug;13(72):132-4.PMID: 15532136 [PubMed - indexed for MEDLINE]9: Sniderman AD.  Is there value in liver function test and creatine phosphokinasemonitoring with statin use? Am J Cardiol. 2004 Nov 4;94(9A):30F-34F. Review.PMID: 15519289 [PubMed - indexed for MEDLINE]10: Johnson TE, Zhang X, Bleicher KB, Dysart G, Loughlin AF, Schaefer WH,Umbenhauer DR.  Statins induce apoptosis in rat and human myotube cultures by inhibitingprotein geranylgeranylation but not ubiquinone. Toxicol Appl Pharmacol. 2004Nov 1;200(3):237-50.  PMID: 15504460 [PubMed - indexed for MEDLINE]11: Davidson MH.  Rosuvastatin safety: lessons from the FDA review and post-approvalsurveillance. Expert Opin Drug Saf. 2004 Nov;3(6):547-57.  PMID: 15500414[PubMed - in process]12: Alsheikh-Ali AA, Kuvin JT, Karas RH.  Risk of adverse events with fibrates. Am J Cardiol. 2004 Oct1;94(7):935-8.  PMID: 15464682 [PubMed - indexed for MEDLINE]13: Baker SK, Goodwin S, Sur M, Tarnopolsky MA.  Cytoskeletal myotoxicity from simvastatin and colchicine. Muscle Nerve.2004 Dec;30(6):799-802. PMID: 15389652 [PubMed - in process]14: Chang JT, Staffa JA, Parks M, Green L.  Rhabdomyolysis with HMG-CoA reductase inhibitors and gemfibrozilcombination therapy. Pharmacoepidemiol Drug Saf. 2004 Jul;13(7):417-26.PMID: 15269925 [PubMed - indexed for MEDLINE]. 15: Maggini M, Raschetti R, Traversa G, Bianchi C, Caffari B, Da Cas R,Panei. P.  The cerivastatin withdrawal crisis: a "post-mortem" analysis. HealthPolicy. 2004 Aug;69(2):151-7. PMID: 15212862 [PubMed - indexed for MEDLINE]16: Rundek T, Naini A, Sacco R, Coates K, DiMauro S.  Atorvastatin decreases the coenzyme Q10 level in the blood of patients atrisk for cardiovascular disease and stroke.Arch Neurol. 2004 Jun;61(6):889-92.PMID: 15210526 [PubMed - indexed for MEDLINE]17: Jamal SM, Eisenberg MJ, Christopoulos S.  Rhabdomyolysis associated with hydroxymethylglutaryl-coenzyme A reductaseinhibitors. Am Heart J. 2004 Jun;147(6):956-65. Review.  PMID: 15199341[PubMed - indexed for MEDLINE]18: Bellosta S, Paoletti R, Corsini A.  Safety of statins: focus on clinical pharmacokinetics and druginteractions. Circulation. 2004 Jun 15;109(23 Suppl 1):III50-7. Review.PMID: 15198967 [PubMed - indexed for MEDLINE]19: Lado Lado FL, Rodriguez Moreno C, Cinza Sajurjo S, Duran Parrondo C,Pazo Nunez M, Lois Pernas A, Masa Vazquez L.  [Statin-induced rhabdomyolysis and renal failure: also with fluvastatine]An Med Interna. 2004 May;21(5):235-7. Spanish. PMID: 15176926 [PubMed -indexed for MEDLINE]20: Takagi S. [Neurological complication due to the drug and the maneuver for thetreatment and prevention of cerebrovascular diseases: iatrogenic neurology]Rinsho Shinkeigaku. 2003 Nov;43(11):877-9. Review. Japanese. PMID: 15152491[PubMed - indexed for MEDLINE]21: Roten L, Schoenenberger RA, Krahenbuhl S, Schlienger RG.  Rhabdomyolysis in association with simvastatin and amiodarone. AnnPharmacother. 2004 Jun;38(6):978-81. Epub 2004 Apr 06.  PMID: 15069169[PubMed - indexed for MEDLINE]22: Fauchais AL, Iba Ba J, Maurage P, Kyndt X, Bataille D, Hachulla E,Parent D, Queyrel V, Lambert M, Michon Pasturel U, Hatron PY, Vanhille P,Devulder B. [Polymyositis induced or associated with lipid-lowering drugs: five cases]Rev Med Interne. 2004 Apr;25(4):294-8. French. PMID: 15050796 [PubMed -indexed for MEDLINE]23: Moosmann B, Behl C.  Selenoprotein synthesis and side-effects of statins. Lancet. 2004 Mar13;363(9412):892-4. Review. PMID: 15031036 [PubMed - indexed for MEDLINE]24: Manhas A, Farmer JA.  Hypolipidemic therapy and cholesterol absorption. Curr Atheroscler Rep.2004 Mar;6(2):89-93. Review. PMID: 15023291 [PubMed - indexed for MEDLINE]25: Koumis T, Nathan JP, Rosenberg JM, Cicero LA.  Strategies for the prevention and treatment of statin-induced myopathy: isthere a role for ubiquinone supplementation? Am J Health Syst Pharm. 2004Mar 1;61(5):515-9. Review. No abstract available.  PMID: 15018231 [PubMed -indexed for MEDLINE]26: Dreier JP, Endres M.  Statin-associated rhabdomyolysis triggered by grapefruit consumption.Neurology. 2004 Feb 24;62(4):670. No abstract available.  PMID: 14981197[PubMed - in process]27: Schaefer WH, Lawrence JW, Loughlin AF, Stoffregen DA, Mixson LA, DeanDC, Raab CE, Yu NX, Lankas GR, Frederick CB.  Evaluation of ubiquinone concentration and mitochondrial function relativeto cerivastatin-induced skeletal myopathy in rats. Toxicol Appl Pharmacol.2004 Jan 1;194(1):10-23.  PMID: 14728975 [PubMed - indexed for MEDLINE]28: Andreou ER, Ledger S.  Potential drug interaction between simvastatin and danazol causingrhabdomyolysis. Can J Clin Pharmacol. 2003 Winter;10(4):172-4. PMID:14712320 [PubMed - indexed for MEDLINE]29: Ehrhardt M, Lindenmaier H, Burhenne J, Haefeli WE, Weiss J.  Influence of lipid lowering fibrates on P-glycoprotein activity in vitro.Biochem Pharmacol. 2004 Jan 15;67(2):285-92.  PMID: 14698041 [PubMed -indexed for MEDLINE]30: Jamil S, Iqbal P.  Rhabdomyolysis induced by a single dose of a statin. Heart. 2004Jan;90(1):e3. PMID: 14676266 [PubMed - indexed for MEDLINE]31: Zeman M, Zak A, Vecka M, Romaniv S.  [Long-term hypolipidemic treatment of mixed hyperlipidemia with acombination of statins and fibrates] Cas Lek Cesk. 2003 Aug;142(8):500-4.Czech. PMID: 14626567 [PubMed - indexed for MEDLINE]32: Foody JM, Krumholz HM.  Are statins indicated for the primary prevention of CAD in octogenarians?antagonist viewpoint. Am J Geriatr Cardiol. 2003 Nov-Dec;12(6):357-60.Review.  PMID: 14610384 [PubMed - indexed for MEDLINE]. 33: Shammas NW, Kapalis MJ, Deckert J, Harris M, Dippel EJ, Labroo A,McKinney. D.  Effectiveness of statin-gemfibrozil combination therapy in patients withmixed hyperlipidemia: experience of a community lipid clinic and safetyreview from the literature. Prev Cardiol. 2003 Fall;6(4):189-94.  PMID:14605512 [PubMed - indexed for MEDLINE]34: Corsini A.  The safety of HMG-CoA reductase inhibitors in special populations at highcardiovascular risk. Cardiovasc Drugs Ther. 2003 May;17(3):265-85. Review.PMID: 14574085 [PubMed - indexed for MEDLINE]35: Klotz U.  Pharmacological comparison of the statins. Arzneimittelforschung.2003;53(9):605-11. Review.  PMID: 14558433 [PubMed - indexed for MEDLINE]36: Newman CB, Palmer G, Silbershatz H, Szarek M.  Safety of atorvastatin derived from analysis of 44 completed trials in9,416 patients. Am J Cardiol. 2003 Sep 15;92(6):670-6.  PMID: 12972104[PubMed - indexed for MEDLINE]37: Kajinami K, Takekoshi N, Saito Y.  Pitavastatin: efficacy and safety profiles of a novel synthetic HMG-CoAreductase inhibitor. Cardiovasc Drug Rev. 2003 Fall;21(3):199-215. Review.PMID: 12931254 [PubMed - indexed for MEDLINE]38: Luh JY, Karnath BM.  Issues in statin-associated myopathy. JAMA. 2003 Aug 20;290(7):888; authorreply 888-9. No abstract available.  PMID: 12928463 [PubMed - indexed forMEDLINE]39: [No authors listed]  Statins: new data in secondary prevention and diabetes. Pravastatin andsimvastatin are the best-assessed statins. Prescrire Int. 2003Aug;12(66):143-8. PMID: 12908497 [PubMed - indexed for MEDLINE]40: Muller T.  [Statin-induced Parkinson's-syndrome. Reader's letter on the article by J.Finsterer in "Der Nervenarzt" (2003) 74:115-122]Nervenarzt. 2003 Aug;74(8):726-7. Epub 2003 May 10.  German. No abstractavailable.PMID: 12904874 [PubMed - indexed for MEDLINE]41: Chuck SK, Penzak SR.  Risk-benefit of HMG-CoA reductase inhibitors in the treatment of HIVprotease inhibitor-related hyperlipidaemia. Expert Opin Drug Saf. 2002May;1(1):5-17. Review.  PMID: 12904155 [PubMed - indexed for MEDLINE]42: Davidson MH. Controversy surrounding the safety of cerivastatin. Expert Opin Drug Saf.2002 Sep;1(3):207-12. Review.  PMID: 12904136 [PubMed - indexed for MEDLINE]43: Jacobson TA.  Combination lipid-lowering therapy with statins: safety issues in thepostcerivastatin era. Expert Opin Drug Saf. 2003 May;2(3):269-86. Review.PMID: 12904106 [PubMed - indexed for MEDLINE]44: Ito MK.  Advances in the understanding and management of dyslipidemia: usingniacin-based therapies. Am J Health Syst Pharm. 2003 Jul 1;60(13 Suppl2):S15-21; quiz S25.  PMID: 12901026 [PubMed - indexed for MEDLINE]45: Parker RA, Huang Q, Tesfamariam B.  Influence of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitorson endothelial nitric oxide synthase and the formation of oxidants in thevasculature. Atherosclerosis. 2003 Jul;169(1):19-29. PMID: 12860247[PubMed - indexed for MEDLINE]46: Andrejak M, Gras V, Massy ZA, Caron J. [Adverse effects of statins] Therapie. 2003 Jan-Feb;58(1):77-83. Review.French. PMID: 12822204 [PubMed - indexed for MEDLINE]47: Wierzbicki AS, Mikhailidis DP, Wray R, Schacter M, Cramb R, Simpson WG,Byrne CB.  Statin-fibrate combination: therapy for hyperlipidemia: a review. Curr MedRes Opin. 2003;19(3):155-68. Review. PMID: 12814127 [PubMed - indexed forMEDLINE]48: Schmitz G, Drobnik W.  Pharmacogenomics and pharmacogenetics of cholesterol-lowering therapy.Clin Chem Lab Med. 2003 Apr;41(4):581-9. Review.  PMID: 12747606 [PubMed -indexed for MEDLINE]49: Bays H, Dujovne C.  Colesevelam HCl: a non-systemic lipid-altering drug. Expert OpinPharmacother. 2003 May;4(5):779-90. Review.  PMID: 12740000 [PubMed -indexed for MEDLINE]50: Paragh G, Balogh Z, Romics L.  [Antilipemic therapy and rhabdomyolysis] Orv Hetil. 2003 Mar16;144(11):515-20. Review.  Hungarian.  PMID: 12731338 [PubMed - indexed forMEDLINE]51: Gotto AM Jr.  Risks and benefits of continued aggressive statin therapy. Clin Cardiol.2003 Apr;26(4 Suppl 3):III3-12. Review. PMID: 12708633 [PubMed - indexed forMEDLINE]52: Thompson PD, Clarkson P, Karas RH.  Statin-associated myopathy. JAMA. 2003 Apr 2;289(13):1681-90. Review.PMID: 12672737 [PubMed - indexed for MEDLINE]53: Clark LT.  Treating dyslipidemia with statins: the risk-benefit profile. Am Heart J.2003 Mar;145(3):387-96. Review.  PMID: 12660659 [PubMed - indexed forMEDLINE]54: Braun RN, Halhuber MJ, Hitzenberger G.  [Information regarding adverse drug effects and treatment indications("package inserts") exemplified by cervistatin (Lipobay)] Wien MedWochenschr. 2003;153(3-4):80-2.  German.  PMID: 12658968 [PubMed - indexedfor MEDLINE]55: [No authors listed]  How a statin might destroy a drug company. Lancet. 2003 Mar8;361(9360):793. No abstract available.  PMID: 12642039 [PubMed - indexedfor MEDLINE]56: Gotto AM Jr.  Safety and statin therapy: reconsidering the risks and benefits. ArchIntern Med. 2003 Mar 24;163(6):657-9. No abstract available.  PMID: 12639194[PubMed - indexed for MEDLINE]57: Ballantyne CM, Corsini A, Davidson MH, Holdaas H, Jacobson TA,Leitersdorf E, Marz W, Reckless JP, Stein EA.  Risk for myopathy with statin therapy in high-risk patients. Arch InternMed. 2003 Mar 10;163(5):553-64. Review.  PMID: 12622602 [PubMed - indexedfor MEDLINE]58: Farmer JA. Statins and myotoxicity. Curr Atheroscler Rep. 2003 Mar;5(2):96-100.Review. PMID: 12573193 [PubMed - indexed for MEDLINE]59: Black C, Jick H.  Etiology and frequency of rhabdomyolysis. Pharmacotherapy. 2002Dec;22(12):1524-6.  PMID: 12495162 [PubMed - indexed for MEDLINE]60: Bolego C, Baetta R, Bellosta S, Corsini A, Paoletti R.  Safety considerations for statins. Curr Opin Lipidol. 2002Dec;13(6):637-44. Review. PMID: 12441888 [PubMed - indexed for MEDLINE]61: Prasad GV, Wong T, Meliton G, Bhaloo S.  Rhabdomyolysis due to red yeast rice (Monascus purpureus) in a renaltransplant recipient. Transplantation. 2002 Oct 27;74(8):1200-1. PMID:12438974 [PubMed - indexed for MEDLINE]62: Lawrence JM, Reckless JP. Fluvastatin. Expert Opin Pharmacother. 2002 Nov;3(11):1631-41. Review.PMID: 12437496 [PubMed - indexed for MEDLINE]63: Mehra MR, Uber PA, Vivekananthan K, Solis S, Scott RL, Park MH, MilaniRV, Lavie CJ.  Comparative beneficial effects of simvastatin and pravastatin on cardiacallograft rejection and survival. J Am Coll Cardiol. 2002 Nov6;40(9):1609-14.  PMID: 12427413 [PubMed - indexed for MEDLINE]64: Kind AH, Zakowski LJ, McBride PE.  Rhabdomyolysis from the combination of a statin and gemfibrozil: anuncommon but serious adverse reaction. WMJ. 2002;101(7):53-6. PMID: 12426921[PubMed - indexed for MEDLINE]65:   Schuff-Werner P, Kohlschein P.  [Current therapy ofhypercholesterolemia. How much statin does your patientneed?]MMW Fortschr Med. 2002 Aug 8;144(31-32):24-6.  German.PMID: 12422725 [PubMed - indexed for MEDLINE]66: Hare CB, Vu MP, Grunfeld C, Lampiris HW.  Simvastatin-nelfinavir interaction implicated in rhabdomyolysis and death.Clin Infect Dis. 2002 Nov 15;35(10):e111-2. Epub 2002 Oct 25.  PMID:12410494 [PubMed - indexed for MEDLINE]67: Talpur R, Ward S, Apisarnthanarax N, Breuer-Mcham J, Duvic M.  Optimizing bexarotene therapy for cutaneous T-cell lymphoma. J Am AcadDermatol. 2002 Nov;47(5):672-84.  PMID: 12399758 [PubMed - indexed forMEDLINE]68: McLaughlin T, Abbasi F, Lamendola C, Leary E, Reaven GM.  Comparison in patients with type 2 diabetes of fibric acid versus hepatichydroxymethyl glutaryl-coenzyme a reductase inhibitor treatment of combineddyslipidemia. Metabolism. 2002 Oct;51(10):1355-9.  PMID: 12370858 [PubMed -indexed for MEDLINE]69: Lewin JJ 3rd, Nappi JM, Taylor MH.  Rhabdomyolysis with concurrent atorvastatin and diltiazem. AnnPharmacother. 2002 Oct;36(10):1546-9.  PMID: 12243603 [PubMed - indexed forMEDLINE]70: Sinzinger H, Chehne F, Lupattelli G.  Oxidation injury in patients receiving HMG-CoA reductase inhibitors:occurrence in patients without enzyme elevation or myopathy. Drug Saf.2002;25(12):877-83.  PMID: 12241128 [PubMed - indexed for MEDLINE]71: Aboulafia DM, Johnston R.  Simvastatin-induced rhabdomyolysis in an HIV-infected patient withcoronary artery disease. AIDS Patient Care STDS. 2000 Jan;14(1):13-8. PMID:12240878 [PubMed - indexed for MEDLINE]72: Evans M, Rees A.  The myotoxicity of statins. Curr Opin Lipidol. 2002 Aug;13(4):415-20.Review. PMID: 12151857 [PubMed - indexed for MEDLINE]73: Evans M, Rees A.  Effects of HMG-CoA reductase inhibitors on skeletal muscle: are allstatins the same?Drug Saf. 2002;25(9):649-63. Review.PMID: 12137559 [PubMed - indexed for MEDLINE]74: Bae J, Jarcho JA, Denton MD, Magee CC.  Statin specific toxicity in organ transplant recipients: case report andreview of the literature. J Nephrol. 2002 May-Jun;15(3):317-9. Review. PMID:12113605 [PubMed - indexed for MEDLINE]75: Williams D, Feely J.  Pharmacokinetic-pharmacodynamic drug interactions with HMG-CoA reductaseinhibitors. Clin Pharmacokinet. 2002;41(5):343-70. Review.  PMID: 12036392[PubMed - indexed for MEDLINE]76: [No authors listed]  Statin stories. Diabetes Obes Metab. 2002 Mar;4(2):138. No abstractavailable.  PMID: 11993442 [PubMed - indexed for MEDLINE]77: Martinez-Castelao A, Ramos R, Gonzalez MT, Castineiras MJ.  [Dyslipidemia and cardiovascular risk in type 2 diabetes mellitus patientswith associated diabetic nephropathy] Nefrologia. 2002;22 Suppl 1:51-8.Spanish.  PMID: 11987671 [PubMed - indexed for MEDLINE]78: Maxa JL, Melton LB, Ogu CC, Sills MN, Limanni A.  Rhabdomyolysis after concomitant use of cyclosporine, simvastatin,gemfibrozil, and itraconazole. Ann Pharmacother. 2002 May;36(5):820-3.PMID: 11978159 [PubMed - indexed for MEDLINE]79: Foxton J. Statin safety. Nurs Stand. 2001 Sep 19-25;16(1):20. No abstract available.PMID: 11977679 [PubMed - indexed for MEDLINE]80: Ambrosi P, Gayet JL, Andrejak M.  [The best of 2001. Clinical pharmacology] Arch Mal Coeur Vaiss. 2002Jan;95 Spec No 1(5 Spec 1):33-8. Review.  French. PMID: 11901897 [PubMed -indexed for MEDLINE]81: Gensini GF, Conti AA, Conti A, Panti A.  [From prevention to cardiovascular rehabilitation: statins andevidence-based medicine] Ital Heart J Suppl. 2002 Jan;3(1):91-4. Review.Italian.PMID: 11899580 [PubMed - indexed for MEDLINE]82: Sica DA, Gehr TW.  3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors andrhabdomyolysis: considerations in the renal failure patient. Curr OpinNephrol Hypertens. 2002 Mar;11(2):123-33. Review.  PMID: 11856903 [PubMed -indexed for MEDLINE]83: Omar MA, Wilson JP.  FDA adverse event reports on statin-associated rhabdomyolysis. AnnPharmacother. 2002 Feb;36(2):288-95. Review.  PMID: 11847951 [PubMed -indexed for MEDLINE]84: Prieto JC. [Safety profile of statins] Rev Med Chil. 2001 Nov;129(11):1237-40.Spanish. PMID: 11836874 [PubMed - indexed for MEDLINE]85: Patel DN, Pagani FD, Koelling TM, Dyke DB, Baliga RR, Cody RJ, Lake KD,Aaronson KD.  Safety and efficacy of atorvastatin in heart transplant recipients. JHeart Lung Transplant. 2002 Feb;21(2):204-10. PMID: 11834348 [PubMed -indexed for MEDLINE]86: Sica DA, Gehr TW.  Rhabdomyolysis and statin therapy: relevance to the elderly. Am J GeriatrCardiol. 2002 Jan-Feb;11(1):48-55. Review.  PMID: 11773716 [PubMed - indexedfor MEDLINE]87: Banga JD.  [Myotoxicity and rhabdomyolisis due to statins] Ned Tijdschr Geneeskd.2001 Dec 8;145(49):2371-6. Review.  Dutch. PMID: 11770264 [PubMed - indexedfor MEDLINE]88: Hamilton-Craig I.  Statin-associated myopathy. Med J Aust. 2001 Nov 5;175(9):486-9. Review.PMID: 11758079 [PubMed - indexed for MEDLINE]89: Bernini F, Poli A, Paoletti R.  Safety of HMG-CoA reductase inhibitors: focus on atorvastatin. CardiovascDrugs Ther. 2001;15(3):211-8. Review.  PMID: 11713888 [PubMed - indexed forMEDLINE]90:   Chazerain P, Hayem G, Hamza S, Best C, Ziza JM.   Four cases oftendinopathy in patients on statin therapy.Joint Bone Spine. 2001 Oct;68(5):430-3.PMID: 11707010 [PubMed - indexed for MEDLINE]91: Holdaas H, Jardine AG, Wheeler DC, Brekke IB, Conlon PJ, Fellstrom B,Hammad A, Holme I, Isoniemi H, Moore R, Rowe PA, Sweny P, Talbot DA,WadstromJ,Ostraat O.  Effect of fluvastatin on acute renal allograft rejection: a randomizedmulticenter trial.Kidney Int. 2001 Nov;60(5):1990-7.PMID: 11703619 [PubMed - indexed for MEDLINE]92: Federman DG, Hussain F, Walters AB.  Fatal rhabdomyolysis caused by lipid-lowering therapy.South Med J. 2001 Oct;94(10):1023-6.PMID: 11702815 [PubMed - indexed for MEDLINE]93: Igel M, Sudhop T, von Bergmann K.  Metabolism and drug interactions of 3-hydroxy-3-methylglutaryl coenzymeA-reductase inhibitors (statins).Eur J Clin Pharmacol. 2001 Aug;57(5):357-64. Review.PMID: 11599653 [PubMed - indexed for MEDLINE]94: Bangratz S.  [Complications in heart transplantation: diagnosis and treatment]Presse Med. 2001 Sep 1;30(24 Pt 2):8-12. Review.  French.PMID: 11577591 [PubMed - indexed for MEDLINE]95: Omar MA, Wilson JP, Cox TS.  Rhabdomyolysis and HMG-CoA reductase inhibitors.Ann Pharmacother. 2001 Sep;35(9):1096-107. Review. Erratum in: AnnPharmacother2001 Oct;35(10):1296.PMID: 11573861 [PubMed - indexed for MEDLINE]96: Boger RH.  Drug interactions of the statins and consequences for drug selection.Int J Clin Pharmacol Ther. 2001 Sep;39(9):369-82. Review.PMID: 11563683 [PubMed - indexed for MEDLINE]97: Comarow A.  Rest easy, statin users. Benefits dwarf risks for these cholesterol drugs.US News World Rep. 2001 Sep 3;131(8):45. No abstract available.PMID: 11550394 [PubMed - indexed for MEDLINE]98:   Shek A, Ferrill MJ. Statin-fibrate combination therapy.Ann Pharmacother. 2001 Jul-Aug;35(7-8):908-17. Review.  PMID: 11485144[PubMed - indexed for MEDLINE]99: Moghadasian MH, Mancini GB, Frohlich JJ.  Pharmacotherapy of hypercholesterolaemia: statins in clinical practice.Expert Opin Pharmacother. 2000 May;1(4):683-95. Review.  PMID: 11249510[PubMed - indexed for MEDLINE]100: Oldemeyer JB, Lund RJ, Koch M, Meares AJ, Dunlay R.  Rhabdomyolysis and acute renal failure after changing statin-fibratecombinations. Cardiology. 2000;94(2):127-8. PMID: 11173785 [PubMed - indexedfor MEDLINE]101: Guyton JR.  Combination drug therapy for combined hyperlipidemia. Curr Cardiol Rep.1999 Sep;1(3):244-50. Review. PMID: 10980849 [PubMed - indexed for MEDLINE]102: Ozdemir O, Boran M, Gokce V, Uzun Y, Kocak B, Korkmaz S.  A case with severe rhabdomyolysis and renal failure associated withcerivastatin-gemfibrozil combination therapy--a case report. Angiology. 2000Aug;51(8):695-7. PMID: 10959522 [PubMed - indexed for MEDLINE]103: Keogh A, Macdonald P, Kaan A, Aboyoun C, Spratt P, Mundy J.  Efficacy and safety of pravastatin vs simvastatin after cardiactransplantation. J Heart Lung Transplant. 2000 Jun;19(6):529-37. PMID:10867332 [PubMed - indexed for MEDLINE]104: Scheen AJ.  [Treatment of combined hyperlipidemia: fibrate and/or statin?] Rev MedLiege. 1999 Jul;54(7):583-7. French. PMID: 10495679 [PubMed - indexed forMEDLINE]105: Guyton JR, Capuzzi DM.  Treatment of hyperlipidemia with combined niacin-statin regimens. Am JCardiol. 1998 Dec 17;82(12A):82U-84U;  discussion 85-86U. Review. PMID:9915667 [PubMed - indexed for MEDLINE]106: Athyros VG, Papageorgiou AA, Hatzikonstandinou HA, Didangelos TP,Carina MV, Kranitsas DF, Kontopoulos AG.  Safety and efficacy of long-term statin-fibrate combinations in patientswith refractory familial combined hyperlipidemia. Am J Cardiol. 1997 Sep1;80(5):608-13.PMID: 9294990 [PubMed - indexed for MEDLINE]107: Laaksonen R, Jokelainen K, Laakso J, Sahi T, Harkonen M, Tikkanen MJ,Himberg JJ.  The effect of simvastatin treatment on natural antioxidants in low-densitylipoproteins and high-energy phosphates and ubiquinone in skeletal muscle.Am J Cardiol. 1996 Apr 15;77(10):851-4.  PMID: 8623738 [PubMed - indexed forMEDLINE]108: Shviro I, Leitersdorf E.  The patient at risk: who should we be treating? Br J Clin Pract Suppl.1996 Jan;77A:24-7. Review. PMID: 8729587 [PubMed - indexed for MEDLINE]109: Peters TK. Safety profile of fluvastatin. Br J Clin Pract Suppl. 1996 Jan;77A:20-3.Review. PMID: 8729586 [PubMed - indexed for MEDLINE]110: Dromer C, Vedrenne C, Billey T, Pages M, Fournie B, Fournie A.  [Rhabdomyolysis due to simvastin. Apropos of a case with review of theliterature] Rev Rhum Mal Osteoartic. 1992 Apr;59(4):281-3. Review.  French.PMID: 1496277 [PubMed - indexed for MEDLINE]STATINS AND LIVER OR KIDNEY DAMAGEFrequently Asked Question: Do statins damage liver or kidneys?Kaplowitz N.  Statin-induced hepatotoxicity. Gastroenterology. 2004 Oct;127(4):1278;author reply 1278-9. No abstract available.  PMID: 15481021 [PubMed -indexed for MEDLINE]Kubota T, Fujisaki K, Itoh Y, Yano T, Sendo T, Oishi R.  Apoptotic injury in cultured human hepatocytes induced by HMG-CoAreductase inhibitors. Biochem Pharmacol. 2004 Jun 15;67(12):2175-86.  PMID:15163549 [PubMed - indexed for MEDLINE]de Denus S, Spinler SA, Miller K, Peterson AM.  Statins and liver toxicity: a meta-analysis. Pharmacotherapy. 2004May;24(5):584-91. Review.  PMID: 15162892 [PubMed - indexed for MEDLINE]   Lado Lado FL, Rodriguez Moreno C, Cinza Sajurjo S, Duran Parrondo C, PazoNunez M, Lois Pernas A, Masa Vazquez L.  [Statin-induced rhabdomyolysis and renal failure: also with fluvastatine]An Med Interna. 2004 May;21(5):235-7. Spanish. PMID: 15176926 [PubMed -indexed for MEDLINE]Jacobson TA.  Combination lipid-lowering therapy with statins: safety issues in thepostcerivastatin era. Expert Opin Drug Saf. 2003 May;2(3):269-86. Review.PMID: 12904106 [PubMed - indexed for MEDLINE]Braun RN, Halhuber MJ, Hitzenberger G.  [Information regarding adverse drug effects and treatment indications("package inserts") exemplified by cervistatin (Lipobay)] Wien MedWochenschr. 2003;153(3-4):80-2. German.  PMID: 12658968 [PubMed - indexedfor MEDLINE]Lewin JJ 3rd, Nappi JM, Taylor MH.  Rhabdomyolysis with concurrent atorvastatin and diltiazem. AnnPharmacother. 2002 Oct;36(10):1546-9.  PMID: 12243603 [PubMed - indexed forMEDLINE]Bae J, Jarcho JA, Denton MD, Magee CC.  Statin specific toxicity in organ transplant recipients: case report andreview of the literature. J Nephrol. 2002 May-Jun;15(3):317-9. Review. PMID:12113605 [PubMed - indexed for MEDLINE]Omar MA, Wilson JP, Cox TS.  Rhabdomyolysis and HMG-CoA reductase inhibitors. Ann Pharmacother. 2001Sep;35(9):1096-107. Review. Erratum in: Ann Pharmacother 2001Oct;35(10):1296. PMID: 11573861 [PubMed - indexed for MEDLINE]Oldemeyer JB, Lund RJ, Koch M, Meares AJ, Dunlay R.  Rhabdomyolysis and acute renal failure after changing statin-fibratecombinations. Cardiology. 2000;94(2):127-8. PMID: 11173785 [PubMed - indexedfor MEDLINE]Ozdemir O, Boran M, Gokce V, Uzun Y, Kocak B, Korkmaz S.  A case with severe rhabdomyolysis and renal failure associated withcerivastatingemfibrozil combination therapy--a case report. Angiology. 2000Aug;51(8):695-7. PMID: 10959522 [PubMed - indexed for MEDLINE]ELDERLY AND STATINSFrequently Asked Question: Should people over 70 take statins?Lack of association between cholesterol and coronary heart disease mortalityand morbidity and all-cause mortality in persons older than 70 years.JAMA. 1994 Nov 2;272(17):1335-40.Krumholz HM, Seeman TE, Merrill SS, Mendes de Leon CF, Vaccarino V,Silverman DI, Tsukahara R, Ostfeld AM, Berkman LF.Department of Internal Medicine, Yale University School of Medicine, NewHaven, CT 06520-8017."CONCLUSIONS--Our findings do not support the hypothesis thathypercholesterolemia or low HDL-C are important risk factors for all-causemortality, coronary heart disease mortality, or hospitalization formyocardial infarction or unstable angina in this cohort of persons olderthan 70 years."Another study showing people over 65 do not benefit from cholesterolreduction:Long-Term Prognostic Importance of Total Cholesterol in Elderly Survivors ofan Acute Myocardial Infarction: The Cooperative Cardiovascular PilotProject.Foody JM, Wang Y, Kiefe CI, Ellerbeck EF, Gold J, Radford MJ, Krumholz HM.Section of Cardiovascular Medicine, Department of Medicine, and Section ofChronic Disease Epidemiology, Department of Epidemiology and Public Health,Yale School of Medicine, New Haven, Connecticut; Qualidigm, Middletown,Connecticut; Yale-New Haven Hospital Center for Outcomes Research andEvaluation, New Haven, Connecticut; Center for Outcome and EffectivenessResearch and Education, University ofAlabama at Birmingham and BirminghamVeterans Affairs Medical Center, Birmingham, Alabama; Department ofPreventive Medicine, University of Kansas School of Medicine, Kansas City,Kansas; and Metastar, Madison, Wisconsin.J Am Geriatr Soc. 2003 Jul;51(7):930-936.  PMID: 12834512"PARTICIPANTS: Four thousand nine hundred twenty-three Medicarebeneficiaries from four states aged 65 and older""CONCLUSION: Among elderly survivors of AMI, elevated total serumcholesterol measured postinfarction is not associated with an increased riskof all-cause mortality in the 6 years after discharge. Furthermore, thisstudy found no evidence of an increased risk of all-cause mortality inpatients with low total cholesterol. Further studies are needed to determinethe relationship of postinfarction lipid subfractions and mortality in olderpatients with coronary artery disease (CAD)."High-density vs low-density lipoprotein cholesterol as the risk factor forcoronary arterydisease and stroke in old age.Weverling-Rijnsburger AW, Jonkers IJ, van Exel E, Gussekloo J, WestendorpRG.Section of Gerontology and Geriatrics, Department of General InternalMedicine, LeidenUniversity Medical Center, Leiden, The Netherlands. a.w.e.weverling-rijnsburger@lumc.eduArch Intern Med. 2003 Jul 14;163(13):1549-54.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1
2860577&dopt=Abstract"In contrast to high LDL cholesterol level, low HDL cholesterol level is arisk factor formortality from coronary artery disease and stroke in old age."Total cholesterol and risk of mortality in the oldest old.Weverling-Rijnsburger AW, Blauw GJ, Lagaay AM, Knook DL, Meinders AE,Westendorp RG.Department of General Internal Medicine, Leiden University Medical Center,TheNetherlands.Lancet. 1997 Oct 18;350(9085):1119-23." In people older than 85 years, high total cholesterol concentrations areassociated withlongevity owing to lower mortality from cancer and infection. The effects ofcholesterol-lowering therapy have yet to be assessed."Golomb BA, Criqui MH, White HL, Dimsdale JE.  The UCSD Statin Study: a randomized controlled trial assessing the impactof statins onselected noncardiac outcomes.Control Clin Trials. 2004 Apr;25(2):178-202.PMID: 15020036 [PubMed - indexed for MEDLINE]Algotsson A, Winblad B.  Patients with Alzheimer's disease may be particularly susceptible toadverse effects ofstatins.Dement Geriatr Cogn Disord. 2004;17(3):109-16. Epub 2004 Jan 20. Review.PMID: 14739530 [PubMed - indexed for MEDLINE]IS THERE AN INDUSTRY BIAS IN STATIN PUBLICATIONS?Why are most studies so positive about statins, and why are there relativelyso few published that show problems?  Do Medical Journals agree that thereis bias in drug-industry funded medical studies?Yes, as does an observational study.Association of Funding and Conclusions in Randomized Drug TrialsA Reflection of Treatment Effect or Adverse Events?http://jama.ama-assn.org/cgi/content/abstract/290/7/921Bodil Als-Nielsen, MD; Wendong Chen, MD; Christian Gluud, MD, DMSc; Lise L.Kjaergard, MDJAMA. 2003;290:921-928 Vol 290 No 7, August 20, 2003"The experimental drug was recommended as treatment of choice in 16% oftrials funded by nonprofit organizations, 30% of trials not reportingfunding, 35% of trials funded by both nonprofit and for-profitorganizations, and 51% of trials funded by for-profit organizations (P<.001;2 test). Logistic regression analyses indicated that funding, treatmenteffect, and double blinding were the only significant predictors ofconclusions. Adjusted analyses showed that trials funded by for-profitorganizations were significantly more likely to recommend the experimentaldrug as treatment of choice (odds ratio, 5.3; 95% confidence interval,2.0-14.4) compared with trials funded by nonprofit organizations. Thisassociation did not appear to reflect treatment effect or adverse events. ""Conclusions Conclusions in trials funded by for-profit organizations maybe more positive due to biased interpretation of trial results. Readersshould carefully evaluate whether conclusions in randomized trials aresupported by data. ""Author Affiliations: The Copenhagen Trial Unit, Center for ClinicalIntervention Research, Copenhagen University Hospital, Copenhagen, Denmark."Clearly JAMA came to the conclusion that funding biases the findings in2002, whenthey quite publicly changed their editorial policy to require fundinginformation forstudies they publish.Further, you are invited to view the British Journal of Medicine, May 31,2003 (Volume326, Issue 7400), which has focused attention on bias and spin inindustry-sponsoredstudies. They carried the following articles athttp://bmj.com/content/vol326/issue7400/#TWIB :Research sponsored by drug companies is biasedhttp://bmj.com/content/vol326/issue7400/twib.shtml#326/7400/0No more free lunchesKamran Abbasi and Richard SmithBMJ 2003; 326: 1155-1156.http://bmj.com/cgi/content/full/326/7400/1155 texthttp://bmj.com/cgi/reprint/326/7400/1155 pdfDrug company sponsorship of education could be replaced at a fraction of itscost  http://bmj.com/cgi/content/full/326/7400/1163 texthttp://bmj.com/cgi/reprint/326/7400/1163 pdfDrug companies advised to publish unfavourable trial resultshttp://bmj.com/cgi/content/full/326/7400/1163-a texthttp://bmj.com/cgi/reprint/326/7400/1163-a pdfWorld body reviews doctors' links to drug industryhttp://bmj.com/cgi/content/abridged/326/7400/1165-a  abridged texthttp://bmj.com/cgi/reprint_abr/326/7400/1165-a abridged pdfhttp://bmj.com/cgi/content/full/326/7400/1165-a  full textPharmaceutical industry sponsorship and research outcome and quality:systematic reviewJoel Lexchin, Lisa A Bero, Benjamin Djulbegovic, and Otavio Clark BMJ 2003;326: 1167-1170. http://bmj.com/cgi/content/full/326/7400/1167  full texthttp://bmj.com/cgi/reprint/326/7400/1167 pdfEvidence b(i)ased medicine-selective reporting from studies sponsored bypharmaceutical industry: review of studies in new drug applicationsHans Melander, Jane Ahlqvist-Rastad, Gertie Meijer, and Bj?rn Beermann BMJ2003; 326: 1171-1173. http://bmj.com/cgi/content/full/326/7400/1171 fulltext http://bmj.com/cgi/reprint/326/7400/1171 pdfCharacteristics of general practitioners who frequently see drug industryrepresentatives: national cross sectional studyChris Watkins, Laurence Moore, Ian Harvey, Patricia Carthy, ElizabethRobinson, and Richard Brawn BMJ 2003; 326: 1178-1179.http://bmj.com/cgi/content/full/326/7400/1178 full texthttp://bmj.com/cgi/reprint/326/7400/1178 pdfWho pays for the pizza? Redefining the relationships between doctors anddrug companies. 1: EntanglementRay Moynihan BMJ 2003; 326: 1189-1192.http://bmj.com/cgi/content/full/326/7400/1189 full texthttp://bmj.com/cgi/reprint/326/7400/1189 pdfWho pays for the pizza? Redefining the relationships between doctors anddrug companies. 2: DisentanglementRay Moynihan BMJ 2003; 326: 1193-1196.http://bmj.com/cgi/content/full/326/7400/1193 full texthttp://bmj.com/cgi/reprint/326/7400/1193 pdfHow to dance with porcupines: rules and guidelines on doctors' relationswith drug companiesElizabeth Wager BMJ 2003; 326: 1196-1198.http://bmj.com/cgi/content/full/326/7400/1196  full texthttp://bmj.com/cgi/reprint/326/7400/1196 pdfHow can research ethics committees protect patients better?Silvio Garattini, Vittorio Bertele, and Luca Li Bassi BMJ 2003; 326:1199-1201. http://bmj.com/cgi/content/full/326/7400/1199 full texthttp://bmj.com/cgi/reprint/326/7400/1199 pdfMedical journals and pharmaceutical companies: uneasy bedfellowsRichard Smith BMJ 2003; 326: 1202-1205.http://bmj.com/cgi/content/full/326/7400/1202 texthttp://bmj.com/cgi/reprint/326/7400/1202 pdfUnhealthy spinBob Burton and Andy Rowell BMJ 2003; 326: 1205-1207.http://bmj.com/cgi/content/full/326/7400/1205 texthttp://bmj.com/cgi/reprint/326/7400/1205 pdfRelationships between the pharmaceutical industry and patients'organisationsAndrew Herxheimer BMJ 2003; 326: 1208-1210.http://bmj.com/cgi/content/full/326/7400/1208 texthttp://bmj.com/cgi/reprint/326/7400/1208 pdfJournals should select drug advertisements more carefullyJames J Oliver and Simon R Maxwell BMJ 2003; 326: 1211.http://bmj.com/cgi/content/full/326/7400/1211Charities and patient groups should declare interestsJenny Hirst BMJ 2003; 326: 1211.http://bmj.com/cgi/content/full/326/7400/1211-aBioethics are difficult to balanceAsad J Raja BMJ 2003; 326: 1215.http://bmj.com/cgi/content/full/326/7400/1215-cThen check out the astonishing articles on medical ghostwriting, starting athttp://www.cbc.ca/consumers/market/files/health/ghostwriting/index.htmlIt may inspire you to earn extra income, because it points out that aMedical Ghostwriter can make $100,000 per year writing favorable drugreports!  YMMVDifficult to question if there is bias in drug-industry studies afterreading the above.Two recent examples of bias in the presentation of pivotal findings are:1) Dr. Gaist's study that proves statins cause polyneuropathyhttp://213.4.18.135/87.pdf.If you read the entire research article, you will note the vast differencebetween hisfindings and the tone of the descriptive abstract, which tends to water downthe findings.Further, the journal ran an editorial that provided further pro-statin spinas damagecontrol.2) The ALLHAT study, published in JAMA, was the largest to date. It ran foryears andencompassed 10,000 people. Their study websitehttp://allhat.sph.uth.tmc.edu/default.htmThese folks were funded by NIH, and they have published what the drugcompanies donot want to hear: that statins do not prevent deaths. Again, there was apro-statin damagecontrol editorial in the same issue, and the news carriers did not highlightthe findings. Infact, CNN buried it inside an article on the other finding: that diureticsworked better thanother blood-pressure medications, where no reader looking for cholesteroldrug resultswould find it.======Glossary of some search terms & equivalents:Lipitor = atorvastatinCoenzyme Q10 = CoQ10 = Ubiquinone = UbidecarenoneStatins = hydroxymethylglutaryl coenzyme A reductase inhibitors = HMG-CoAReductase InhibitorsLipitor, Mevacor, Pravachol, Zocor, Lescol, and Baycol = atorvastatin,cerivastatin,fluvastatin, lovastatin, pravastatin, and simvastatin