Statin Adverse Effects FAQ: ELDERLY AND STATINS

(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. )

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

In Canada:

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

PharmaWatch:
http://www.pharmawatch.net/

Thank you

ELDERLY AND STATINS

References (updated as of  January 7, 2005):

Lack of a_ssociation between cholesterol and coronary heart disease
mortality
and morbidity and all-cause mortality in persons older than 70 years.
JAMA. 1994 Nov 2;272(17):1335-40.
Krumholz HM, Seeman TE, Merrill SS, Mendes de Leon CF, Vaccarino V,
Silverman DI, Tsukahara R, Ostfeld AM, Berkman LF.
Department of Internal Medicine, Yale University School of Medicine, New
Haven, CT 06520-8017.

"CONCLUSIONS--Our findings do not support the hypothesis that
hypercholesterolemia or low HDL-C are important risk factors for all-cause
mortality, coronary heart disease mortality, or hospitalization for
myocardial infarction or unstable angina in this cohort of persons older
than 70 years."

Another study showing people over 65 do not benefit from cholesterol
reduction:

Long-Term Prognostic Importance of Total Cholesterol in Elderly Survivors of
an Acute Myocardial Infarction: The Cooperative Cardiovascular Pilot
Project.
Foody JM, Wang Y, Kiefe CI, Ellerbeck EF, Gold J, Radford MJ, Krumholz HM.
Section of Cardiovascular Medicine, Department of Medicine, and Section of
Chronic Disease Epidemiology, Department of Epidemiology and Public Health,
Yale School of Medicine, New Haven, Connecticut; Qualidigm, Middletown,
Connecticut; Yale-New Haven Hospital Center for Outcomes Research and
Evaluation, New Haven, Connecticut; Center for Outcome and Effectiveness
Research and Education, University ofAlabama at Birmingham and Birmingham
Veterans Affairs Medical Center, Birmingham, Alabama; Department of
Preventive Medicine, University of Kansas School of Medicine, Kansas City,
Kansas; and Metastar, Madison, Wisconsin.
J Am Geriatr Soc. 2003 Jul;51(7):930-936.   PMID: 12834512

"PARTICIPANTS: Four thousand nine hundred twenty-three Medicare
beneficiaries from four states aged 65 and older"

"CONCLUSION: Among elderly survivors of AMI, elevated total serum
cholesterol measured postinfarction is not a_ssociated with an increased
risk
of all-cause mortality in the 6 years after discharge. Furthermore, this
study found no evidence of an increased risk of all-cause mortality in
patients with low total cholesterol. Further studies are needed to determine
the relationship of postinfarction lipid subfractions and mortality in older
patients with coronary artery disease (CAD)."

Patients with Alzheimer's disease may be particularly susceptible to adverse
effects of statins.
Algotsson A, Winblad B.
Dement Geriatr Cogn Disord. 2004;17(3):109-16. Epub 2004 Jan 20.
Department of Clinical Neuroscience, Occupational Therapy and Elderly Care
Research, Division of Geriatric Medicine, Karolinska Institute, Huddinge
University Hospital, Huddinge, Sweden.

In epidemiological, cross-sectional studies, treatment with
3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins)
prevented to a large extent the development of Alzheimer's disease (AD), but
the results of randomized, placebo-controlled studies, focused on statin
therapy in patients with ischemic heart disease (IHD), are at variance.
Nonetheless, data from epidemiological, longitudinal studies in humans as
well as studies on transgenic mouse models and cultured neuronal cell lines
indicate that cholesterol may contribute to the pathogenesis of AD. Statins
have proven therapeutic and preventive effects in IHD and other vascular
diseases in man. They generally are well tolerated, but some adverse
effects, probably due to antiproliferative and proapoptotic properties of
the statins, are matters of concern. AD patients may be extrasusceptible to
adverse effects of statins due to preexisting aberrations in signal
transduction and energy metabolism in the neurons and a perturbed
cholesterol metabolism in the brain. This problem might be addressed in
randomized, double-blind studies with statins in AD. The statins differ from
each other in several aspects, and they are not considered to be
therapeutically interchangeable. It could be fruitful to use both a placebo
and two different types of statins, i.e. an essentially hydrophilic statin
and a lipophilic statin, in a double-blinded fashion, and to compare the
effects on the cognitive decline in AD. Copyright 2004 S. Karger AG, Basel
Publication Types:

?         Review

?         Review, Tutorial

PMID: 14739530 [PubMed - indexed for MEDLINE]

Lipid-lowering agents and the risk of hip fracture in a Medicaid population.
Ray WA, Daugherty JR, Griffin MR.
Inj Prev. 2002 Dec;8(4):276-9.
Department of Preventive Medicine, Vanderbilt University School of Medicine
and the Geriatric Research, Education and Clinical Center, Nashville VAMC,
Nashville, Tennessee 37232, USA. wayne.ray@mcmail.vanderbilt.edu
"CONTEXT: Three recent nested case-control studies conducted in automated
databases suggest that users of 3-hydroxy-3-methylglutaryl coenzyme A
reductase inhibitors (statins) have a risk of hip and other osteoporotic
fractures half that of non-users of any lipid-lowering drug. However, this
comparison may be biased by unmeasured factors a_ssociated with treated
hyperlipidemias. OBJECTIVE: To compare the risk of hip fracture among users
of statins and other lipid-lowering agents, which is less susceptible to
bias than the comparisons performed in the previous studies. DESIGN AND
SETTING: Retrospective cohort study conducted in the Tennessee Medicaid
program between 1 January 1989 through 31 December 1998. SUBJECTS: New users
of all lipid-lowering drugs and randomly selected non-user controls who at
baseline were at least 50 years of age and did not have life threatening
illness, nursing home residence, or diagnosed dementia or osteoporosis.
There were 12506 persons with new use of statins, 4798 with new use of other
lipid lowering drugs, and 17280 non-user controls. MAIN OUTCOME MEASURE:
Fracture of the proximal femur (hip), excluding pathological fractures or
those resulting from severe trauma. RESULTS: During 66690 person years of
follow up, there were 186 hip fractures (2.8 per 1000). Relative to
non-users, the adjusted incidence rate ratios (95% confidence interval) were
0.62 (0.45 to 0.85) for statin users and 0.44 (0.26 to 0.95) for other
lipid-lowering drugs. When compared directly with the other drugs, the
adjusted incidence rate ratio for statins was 1.42 (0.83-2.43). CONCLUSION:
These data provide evidence that the previously observed protective effect
of statins may be explained by unmeasured confounding factors.
PMID: 12460961 [PubMed - indexed for MEDLINE]"

Age and gender bias in statin trials.
Bandyopadhyay S, Bayer AJ, O'Mahony MS.
QJM. 2001 Mar;94(3):127-32.
University Department of Geriatric Medicine, Llandough Hospital, Penarth,
UK.
Cardiovascular disease is strongly age-related, and is the leading cause of
death in older people. Several well-publicized trials have recently reported
that statin drugs (HMG CoA reductase inhibitors) are effective in lowering
cholesterol and in reducing the risk of myocardial infarction and stroke. In
order to determine whether the results of these trials are relevant to our
ageing population, we examined the representation of older people and women
in randomized controlled trials of statin drugs. A systematic search of the
medical literature from 1990 to 1999 was done to identify randomized
placebo-controlled trials of statin drugs which evaluated clinical
end-points-myocardial infarction, stroke or death. We identified 19 trials:
15 secondary prevention and four primary prevention. The mean age, age range
and gender of the participants in these trials were determined. In the
secondary prevention trials, the total number of patients randomized was
31683, with a combined mean age of 58.1 years. No trial enrolled people
beyond the age of 75 years, and only 23% of the trial population was female.
The four primary prevention trials randomized a combined total of 14 557
subjects with a mean age of 56.9 years. Only 10% of study participants were
female. Statin drug trials have suffered from age and gender bias, having
been mainly conducted in middle-aged male populations. The extrapolation of
evidence from these trials to older people and women needs further
evaluation.
Publication Types: Review

PMID: 11259687 [PubMed - indexed for MEDLINE]

High-density vs low-density lipoprotein cholesterol as the risk factor for
coronary artery disease and stroke in old age.
Weverling-Rijnsburger AW, Jonkers IJ, van Exel E, Gussekloo J, Westendorp
RG.
Section of Gerontology and Geriatrics, Department of General Internal
Medicine, Leiden University Medical Center, Leiden, The Netherlands.
a.w.e.weverling-rijnsburger@lumc.edu

Arch Intern Med. 2003 Jul 14;163(13):1549-54.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1
2860577&dopt=Abstract

"In contrast to high LDL cholesterol level, low HDL cholesterol level is a
risk factor for mortality from coronary artery disease and stroke in old
age."

Total cholesterol and risk of mortality in the oldest old.
Weverling-Rijnsburger AW, Blauw GJ, Lagaay AM, Knook DL, Meinders AE,
Westendorp RG.
Department of General Internal Medicine, Leiden University Medical Center,
The Netherlands.

Lancet. 1997 Oct 18;350(9085):1119-23.

" In people older than 85 years, high total cholesterol concentrations are
a_ssociated with longevity owing to lower mortality from cancer and
infection. The effects of cholesterol-lowering therapy have yet to be
a_ssessed."

Golomb BA, Criqui MH, White HL, Dimsdale JE.

The UCSD Statin Study: a randomized controlled trial a_ssessing the impact
of statins on selected noncardiac outcomes.

Control Clin Trials. 2004 Apr;25(2):178-202.

PMID: 15020036 [PubMed - indexed for MEDLINE]

Dermatomyositis-like syndrome and HMG-CoA reductase inhibitor (statin)
intake.
Muscle Nerve. 2004 Dec;30(6):803-7.
Vasconcelos OM, Campbell WW.
Department of Neurology, Uniformed Services University of the Health
Sciences, Bethesda, Maryland, USA.
A patient developed an adult-onset dermatomyositis-like syndrome
characterized by skin rash and progressive proximal muscle weakness
concurrent with the intake of simvastatin. Despite discontinuation of the
statin, symptoms progressed and required conventional steroid therapy for
remission. The a_ssociation between statins and the development of a
musculocutaneous syndrome closely resembling dermatomyositis in susceptible
subjects is poorly understood and has been reported rarely. The purpose of
this report is to provide additional support for this pathological
a_ssociation. Since the population receiving statins is large and rapidly
growing, caregivers are urged to be alert regarding the early recognition
and proper care of the spectrum of neuromuscular complications linked to
statin intake.
Publication Types:  Case Reports
PMID: 15389654 [PubMed - indexed for MEDLINE]