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Jason
medicine forum Guru
Joined: 29 Apr 2005
Posts: 1120
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 Posted: Wed May 31, 2006 11:24 pm Post subject:
Statins and Low-Grade Myopathy
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Statins and Low-Grade Myopathy
Statins (hydroxymethyl glutaryl coenzyme A reductase
inhibitors) are highly effective drugs for reducing serum
cholesterol and low-density lipoprotein cholesterol levels.
Clinical trials have shown that they also reduce risk for
coronary heart disease events, coronary procedures, and
stroke by about one third (1). Millions of people in the
United States and worldwide are being treated with statins.
In clinical trials and in clinical practice, statins have proved
to be remarkably safe.
The one notable side effect of statin therapy is myopathy.
A small fraction of patients who are treated with
statins will develop severe myopathy (2). In the worst cases,
severe myoglobinuria, acute renal failure, and even death
can occur. The incidence of severe myopathy is low, perhaps
1 in 1000 patients (2). Predisposing factors for severe
myopathy appear to include advanced age, relatively low
body weight, female sex, certain medications, use of multiple
medications, multisystem disease, and acute illnesses
or major surgery (3). If statins were avoided or used in low
doses in these circumstances, it is likely that the incidence
of severe myopathy could be greatly reduced.
Less severe forms of myopathy undoubtedly occur. In
some patients, fatigue and muscle pain and weakness develop
with moderately high serum creatine kinase levels
but not acute renal failure. In these cases, the myopathy
resolves when statin therapy is discontinued.
Still more patients report various muscle symptoms‹
fatigue, pain, and muscle weakness‹but have normal creatine
kinase levels. These symptoms probably are unrelated
to statin therapy in many patients. In middle-aged and
older people, muscle, joint, and tendon symptoms are very
common. Naturally, if a patient takes a medication that is
believed to produce muscle problems, symptoms are often
attributed to the medication. On the other hand, the major
controlled clinical trials have not detected a higher prevalence
of muscle symptoms during statin therapy versus placebo
(1). This failure of detection has generally led clinical
trialists to conclude that statin-associated myopathy with
normal creatine kinase levels essentially does not exist or
that, if it does exist, it cannot be detected above the ³background
noise² of muscle symptoms in the general clinical-trial
population.
Many physicians in clinical practice nonetheless believe
that they can identify a subset of statin-treated patients
who have a unique set of statin-related muscle symptoms.
Some patients clearly relate the onset of muscle
symptoms to initiation of statin therapy. These symptoms
may abate after discontinuation of therapy, only to reappear
when statin therapy is restarted. The number of such
patients is not large, and thus it may have been impossible
to identify them in large clinical trials.
In this issue, Phillips and colleagues (4) report on a set
of studies in four patients who had muscle symptoms during-
statin therapy that resolved during placebo use. Quantitatively
measured muscle weakness also resolved during
placebo use. Muscle biopsies were performed in three patients
during statin therapy and then during placebo use.
Several pathologic changes were seen on biopsy specimens
obtained during statin therapy: increased lipid content of
mitochondria, fibers that did not stain for cytochrome oxidase
activity, and ragged red fibers. The authors suggest
that these patients had statin-associated myopathy with
normal serum creatine kinase levels.
Despite the study¹s small size, we cannot dismiss these
observations as random variation in muscle structure.
However, these highly suggestive results are clearly preliminary.
The number of patients was small, and all appropriate
controls were not used. Nonetheless, this study is novel
because it used quantitative measures of muscle strength
and muscle biopsy to address the question of myopathy
with normal creatine kinase levels during statin therapy.
To be confirmed, the current data would have to be
extended to many more patients in whom muscle symptoms
are closely correlated with statin use. Reproducibility
of symptoms during therapy and symptom resolution after
discontinuation of statin therapy would be necessary. A
definitive study would have to be carefully designed and
executed. It would need to be double-blinded and placebo-controlled
and include sufficient numbers of patients to
provide a valid statistical comparison. In addition, investigators
would have to carefully consider the appropriate
selection of patients. The development of a registry of candidate
patients at multiple sites could facilitate a multi-center
study.
Is a carefully controlled, sizable study of this type
worth the investment of time and effort? To date, no evidence
indicates that prolonged statin therapy leads to permanent
muscle damage or progressive myopathy in patients
with normal creatine kinase levels. Controlled
clinical trials attest to the general safety of statins, and
symptomatic side effects appear to be limited to a relatively
small proportion of treated patients. In addition, no therapy
prevents or treats statin-induced myopathy, short of
withholding the drug. On the other hand, statins are being
prescribed to millions of people, and are usually continued
throughout the patient¹s lifetime. It is certain that statins
cause myopathy in some patients. For these reasons, a valid
argument can be made for a more extensive study of low-grade
myopathy in patients treated with statins.
In the meantime, physicians should recognize the great
benefit of statin therapy in high-risk patients and their
documented safety for most patients. For high-risk persons,
the proven efficacy for preventing cardiovascular disease
outweighs the unlikely possibility of permanent muscle
damage. Phillips and colleagues¹ preliminary results
certainly do not provide adequate information on the spec-
spectrum, scope, or prognosis of myopathy with normal creatine
kinase levels during statin therapy. For these reasons,
prescription of statins for eligible patients should continue
despite the current results. Moreover, before discontinuing
therapy, physicians should carefully evaluate any patient
receiving statins who reports muscle symptoms. In most
cases, the symptoms will be found not to be consistent
with chronic myopathy, and often they will not be related
temporally to statin treatment. High-risk patients in particular
should not be deprived of major cardiovascular risk
reduction just because they display symptoms not clearly
documented to be closely related to statin therapy.
Despite these comments, the actions of statin on muscle
metabolism and structure deserve further investigation
to clarify the confusing area of low-grade myopathy apparently
associated with statin use in a few patients.
Scott M. Grundy, MD, PhD
University of Texas Southwestern Medical Center at Dallas
Dallas, TX 75390-9052
Current Author Address: Scott M. Grundy, MD, PhD, Center for
Human Nutrition and the Departments of Clinical Nutrition and Inter-
Internal Medicine, University of Texas Southwestern Medical Center at Dallas,
5323 Harry Hines Boulevard, Y3.206, Dallas, TX 75390-9052.
Potential Financial Conflicts of Interest: Honoraria (from Merck &
Co.; Pfizer, Inc.; Bristol-Myers Squibb; and Bayer); Grants (from Merck
& Co. and Pfizer, Inc.)
Ann Intern Med. 2002;137:617-618.
References
1. Executive Summary of The Third Report of The National Cholesterol Education
Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment
of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;
285:2486-97. [PMID: 11368702]
2. Staffa JA, Chang J, Green L. Cerivastatin and reports of fatal rhabdomyolysis
[Letter]. N Engl J Med. 2002;346:539-40. [PMID: 11844864]
3. Pasternak RC, Smith SC, Bairey-Merz CN, Grundy SM, Cleeman JI, Len-fant
C. ACC/AHA/NHLBI clinical advisory on the use and safety of statins (1)
(2). J Am Coll Cardiol. 2002;40:567-72. [PMID: 12142128]
4. Phillips PS, Haas RH, Bannykh S, Hathaway S, Gray NL, Kimura BJ, et al.
Statin-associated myopathy with normal creatine kinase levels. The Scripps Mercy
Clinical Research Center. Ann Intern Med. 2002;137:581-5.
© 2002 American College of PhysiciansAmerican Society of Internal
Medicine
Statins and Low-Grade Myopathy
618 1 October 2002 Annals of Internal Medicine Volume 137 € Number 7
www.annals.org |
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eml
medicine forum Guru Wannabe
Joined: 12 Jun 2005
Posts: 135
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| Posted: Thu Jun 01, 2006 3:29 pm Post subject:
Re: Statins and Low-Grade Myopathy
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Jason Johnson wrote:
| Quote: | Statins and Low-Grade Myopathy
In clinical trials and in clinical practice, statins have proved
to be remarkably safe.
The one notable side effect of statin therapy is myopathy.
A small fraction of patients who are treated with
statins will develop severe myopathy
|
eml wrote:
the following is from an unbiased clinician (has not made his
reputation on statins, does not research statins, nor is he funded by
the statin industry):
Underappreciated Statin-Induced Myopathic Weakness Causes Disability
Bruce H. Dobkin
University of California Los Angeles, Reed Neurologic Research Center,
bdobkin@mednet.ucla.edu
Introduction. Myopathic syndromes induced by 3-hydroxy-3-methylglutaryl
coenzyme A (HMG-CoA) reductase inhibitors (statins) include muscle
complaints, myalgia, myositis, and rhabdomyolysis. No prospective study
of statins, however, included tests of strength, so the incidence of
weakness, with or without muscle symptoms and elevated enzymes, is
unknown, and perhaps overlooked. Methods. From a convenience sample of
patients referred to an outpatient neurorehabilitation clinic over the
course of 1 year, 8 patients with hemiparetic stroke and 10 patients
with other presumed neurologic diseases presented with new difficulty
walking by 3 to 12 months after starting one of 3 statins. They
reported no myalgias, exercise-induced aches, or weakness. Examination
revealed proximal paresis graded 4/5 on the unaffected side in the
hemiparetic patients and symmetrical bilateral proximal limb and neck
flexor weakness graded 4/5 in the others. They stood up with difficulty
and walked with bilateral hip drop and imbalance on turns. Results.
Laboratory tests did not reveal myositis or other causes for paresis.
No improvement in strength or mobility was found 6 weeks after
initiating resistance exercises. The statin agent was stopped. By 3
months off statin, all recovered 5/5 proximal strength. Walking
improved, and they arose from a chair without pushing off with their
arms. Discussion. Serial manual muscle testing after initiating a
statin may detect a reversible cause of disability. A genetic
predisposition to statin-induced myopathic proximal weakness with
normal creatine kinase is consistent with a continuum of previously
reported symptoms and signs but may be underappreciated.
(in the discussion, the author notes that while single-subject,
double-blinded statins vs placebo studies would make the causal
relationship between disabling myopathy more apparent, he notes
recurrences in his patients' symptoms when the investigator was unaware
that several of the subjects had been placed back on the statin by
their primary physicians. p. 261) |
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Jason
medicine forum Guru
Joined: 29 Apr 2005
Posts: 1120
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| Posted: Thu Jun 01, 2006 4:59 pm Post subject:
Re: Statins and Low-Grade Myopathy
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In article <1149175772.834853.94160@i39g2000cwa.googlegroups.com>, "eml"
<mmlevy46@hotmail.com> wrote:
Jason Johnson wrote:
| Quote: | Statins and Low-Grade Myopathy
In clinical trials and in clinical practice, statins have proved
to be remarkably safe.
The one notable side effect of statin therapy is myopathy.
A small fraction of patients who are treated with
statins will develop severe myopathy
|
eml wrote:
the following is from an unbiased clinician (has not made his
reputation on statins, does not research statins, nor is he funded by
the statin industry):
Underappreciated Statin-Induced Myopathic Weakness Causes Disability
Bruce H. Dobkin
University of California Los Angeles, Reed Neurologic Research Center,
bdobkin@mednet.ucla.edu
Introduction. Myopathic syndromes induced by 3-hydroxy-3-methylglutaryl
coenzyme A (HMG-CoA) reductase inhibitors (statins) include muscle
complaints, myalgia, myositis, and rhabdomyolysis. No prospective study
of statins, however, included tests of strength, so the incidence of
weakness, with or without muscle symptoms and elevated enzymes, is
unknown, and perhaps overlooked. Methods. From a convenience sample of
patients referred to an outpatient neurorehabilitation clinic over the
course of 1 year, 8 patients with hemiparetic stroke and 10 patients
with other presumed neurologic diseases presented with new difficulty
walking by 3 to 12 months after starting one of 3 statins. They
reported no myalgias, exercise-induced aches, or weakness. Examination
revealed proximal paresis graded 4/5 on the unaffected side in the
hemiparetic patients and symmetrical bilateral proximal limb and neck
flexor weakness graded 4/5 in the others. They stood up with difficulty
and walked with bilateral hip drop and imbalance on turns. Results.
Laboratory tests did not reveal myositis or other causes for paresis.
No improvement in strength or mobility was found 6 weeks after
initiating resistance exercises. The statin agent was stopped. By 3
months off statin, all recovered 5/5 proximal strength. Walking
improved, and they arose from a chair without pushing off with their
arms. Discussion. Serial manual muscle testing after initiating a
statin may detect a reversible cause of disability. A genetic
predisposition to statin-induced myopathic proximal weakness with
normal creatine kinase is consistent with a continuum of previously
reported symptoms and signs but may be underappreciated.
(in the discussion, the author notes that while single-subject,
double-blinded statins vs placebo studies would make the causal
relationship between disabling myopathy more apparent, he notes
recurrences in his patients' symptoms when the investigator was unaware
that several of the subjects had been placed back on the statin by
their primary physicians. p. 261)
Thanks for your post. If possible, try to find a research report related
to Rhabdomyolyis. I found several research reports related to
Statin-Induced Myopathic but could not find any research reports related to
Statin-Induced Rhabdomyolysis.
I found this information in a research report I found in the Journal
of the American College of Cardiology (Vol. 40, No. 3,2002)
"...It is rare that patients treated with a statin exhibit severe
myositis.... In this setting, failure to discontinue drug therapy
can lead to rhabdomyoysis and acute renal necrosis..."
JAMA 1990 264:71-95
In other words, if any statin patients develop severe myositis (severe
muscle pain), they should see their doctors ASAP.
Jason |
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William Wagner
medicine forum Guru
Joined: 29 Apr 2005
Posts: 809
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| Posted: Thu Jun 01, 2006 5:09 pm Post subject:
Re: Statins and Low-Grade Myopathy
|
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|
In article
<jason-0106060959230001@66-52-22-15.lsan.pw-dia.impulse.net>,
jason@nospam.com (Jason Johnson) wrote:
| Quote: | In article <1149175772.834853.94160@i39g2000cwa.googlegroups.com>, "eml"
mmlevy46@hotmail.com> wrote:
Jason Johnson wrote:
Statins and Low-Grade Myopathy
In clinical trials and in clinical practice, statins have proved
to be remarkably safe.
The one notable side effect of statin therapy is myopathy.
A small fraction of patients who are treated with
statins will develop severe myopathy
eml wrote:
the following is from an unbiased clinician (has not made his
reputation on statins, does not research statins, nor is he funded by
the statin industry):
Underappreciated Statin-Induced Myopathic Weakness Causes Disability
Bruce H. Dobkin
University of California Los Angeles, Reed Neurologic Research Center,
bdobkin@mednet.ucla.edu
Introduction. Myopathic syndromes induced by 3-hydroxy-3-methylglutaryl
coenzyme A (HMG-CoA) reductase inhibitors (statins) include muscle
complaints, myalgia, myositis, and rhabdomyolysis. No prospective study
of statins, however, included tests of strength, so the incidence of
weakness, with or without muscle symptoms and elevated enzymes, is
unknown, and perhaps overlooked. Methods. From a convenience sample of
patients referred to an outpatient neurorehabilitation clinic over the
course of 1 year, 8 patients with hemiparetic stroke and 10 patients
with other presumed neurologic diseases presented with new difficulty
walking by 3 to 12 months after starting one of 3 statins. They
reported no myalgias, exercise-induced aches, or weakness. Examination
revealed proximal paresis graded 4/5 on the unaffected side in the
hemiparetic patients and symmetrical bilateral proximal limb and neck
flexor weakness graded 4/5 in the others. They stood up with difficulty
and walked with bilateral hip drop and imbalance on turns. Results.
Laboratory tests did not reveal myositis or other causes for paresis.
No improvement in strength or mobility was found 6 weeks after
initiating resistance exercises. The statin agent was stopped. By 3
months off statin, all recovered 5/5 proximal strength. Walking
improved, and they arose from a chair without pushing off with their
arms. Discussion. Serial manual muscle testing after initiating a
statin may detect a reversible cause of disability. A genetic
predisposition to statin-induced myopathic proximal weakness with
normal creatine kinase is consistent with a continuum of previously
reported symptoms and signs but may be underappreciated.
(in the discussion, the author notes that while single-subject,
double-blinded statins vs placebo studies would make the causal
relationship between disabling myopathy more apparent, he notes
recurrences in his patients' symptoms when the investigator was unaware
that several of the subjects had been placed back on the statin by
their primary physicians. p. 261)
Thanks for your post. If possible, try to find a research report related
to Rhabdomyolyis. I found several research reports related to
Statin-Induced Myopathic but could not find any research reports related to
Statin-Induced Rhabdomyolysis.
I found this information in a research report I found in the Journal
of the American College of Cardiology (Vol. 40, No. 3,2002)
"...It is rare that patients treated with a statin exhibit severe
myositis.... In this setting, failure to discontinue drug therapy
can lead to rhabdomyoysis and acute renal necrosis..."
JAMA 1990 264:71-95
In other words, if any statin patients develop severe myositis (severe
muscle pain), they should see their doctors ASAP.
Jason
|
I did and my Cardio guy made a note of as did my PCP. A few times.
This for two years after being on lesser statins for about three.
Cardio guy increased my lipitor from 20 to 80 and it was not good for
me. Down hill real quick . Like I mention often measure your calfs!!
Bill who is off all Doc's and trying to get BP happy.
LDL 160 HDL 70 and throw in CABG.
--
S Jersey USA Zone 5 Shade
This article is posted under fair use rules in accordance with
Title 17 U.S.C. Section 107, and is strictly for the educational
and informative purposes. This material is distributed without profit. |
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marcia
medicine forum addict
Joined: 03 May 2006
Posts: 79
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| Posted: Thu Jun 01, 2006 6:04 pm Post subject:
Re: Statins and Low-Grade Myopathy
|
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|
Jason Johnson wrote:
| Quote: | Thanks for your post. If possible, try to find a research report related
to Rhabdomyolyis. I found several research reports related to
Statin-Induced Myopathic but could not find any research reports related to
Statin-Induced Rhabdomyolysis.
I found this information in a research report I found in the Journal
of the American College of Cardiology (Vol. 40, No. 3,2002)
"...It is rare that patients treated with a statin exhibit severe
myositis.... In this setting, failure to discontinue drug therapy
can lead to rhabdomyoysis and acute renal necrosis..."
JAMA 1990 264:71-95
In other words, if any statin patients develop severe myositis (severe
muscle pain), they should see their doctors ASAP.
Jason
|
Jason,
Pub Med pulls about 26 pages of articles on the search "rhabdomyolysis
statin" I've included links and abstracts to the ones that seemed most
relevent to your concerns.
If you have access to journal databases through your college or
community library, you might want to search there, also. They often
have full-text articles available at no cost to the consumer.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16716459&query_hl=2&itool=pubmed_docsum
Rev Med Interne. 2006 May 3; [Epub ahead of print]
Related Articles, Links
Â
[Rhabdomyolysis induced by fenofibrate monotherapy.]
[Article in French]
Archambeaud-Mouveroux F, Lopez S, Combes C, Lassandre S, Amaniou M,
Teissier MP, Galinat S.
Service de medecine interne B-d'endocrinologie, hopital du Cluzeau, 23,
avenue Dominique-Larrey, 87042 Limoges, France.
INTRODUCTION: Rhabdomyolysis with fibrate have been reported when
fibrate are associated with statin or during renal insufficiency or
hypothyroidism. CASE RECORD: We describe one patient with diabetes
mellitus treated by fenofibrate monotherapy since several years; 48 h
after gliclazide therapy was introduced, rhabdomyolysis occurred.
DISCUSSION: Responsibilities of deshydratation and / or drug
interaction with gliclazide. are discussed.
PMID: 16716459 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16671104&query_hl=2&itool=pubmed_docsum
1: Muscle Nerve. 2006 May 2; [Epub ahead of print]
Related Articles, Links
Â
Genetic risk factors associated with lipid-lowering drug-induced
myopathies.
Vladutiu GD, Simmons Z, Isackson PJ, Tarnopolsky M, Peltier WL, Barboi
AC, Sripathi N, Wortmann RL, Phillips PS.
Department of Pediatrics, School of Medicine and Biomedical Sciences,
State University of New York at Buffalo, 936 Delaware Avenue, Buffalo,
New York 14209, USA.
Lipid-lowering drugs produce myopathic side effects in up to 7% of
treated patients, with severe rhabdomyolysis occurring in as many as
0.5%. Underlying metabolic muscle diseases have not been evaluated
extensively. In a cross-sectional study of 136 patients with
drug-induced myopathies, we report a higher prevalence of underlying
metabolic muscle diseases than expected in the general population.
Control groups included 116 patients on therapy with no myopathic
symptoms, 100 asymptomatic individuals from the general population
never exposed to statins, and 106 patients with non-statin-induced
myopathies. Of 110 patients who underwent mutation testing, 10% were
heterozygous or homozygous for mutations causing three metabolic
myopathies, compared to 3% testing positive among asymptomatic patients
on therapy (P = 0.04). The actual number of mutant alleles found in the
test group patients was increased fourfold over the control group (P <
0.0001) due to an increased presence of mutation homozygotes. The
number of carriers for carnitine palmitoyltransferase II deficiency and
for McArdle disease was increased 13- and 20-fold, respectively, over
expected general population frequencies. Homozygotes for myoadenylate
deaminase deficiency were increased 3.25-fold with no increase in
carrier status. In 52% of muscle biopsies from patients, significant
biochemical abnormalities were found in mitochondrial or fatty acid
metabolism, with 31% having multiple defects. Variable persistent
symptoms occurred in 68% of patients despite cessation of therapy. The
effect of statins on energy metabolism combined with a genetic
susceptibility to triggering of muscle symptoms may account for
myopathic outcomes in certain high-risk groups. Muscle Nerve, 2006.
PMID: 16671104 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16651050&query_hl=2&itool=pubmed_docsum
1: Am J Med. 2006 May;119(5):400-9.
Related Articles, Links
Â
Clinical perspectives of statin-induced rhabdomyolysis.
Antons KA, Williams CD, Baker SK, Phillips PS.
Scripps Mercy Clinical Research Center, Scripps Mercy Hospital, San
Diego, Calif 92103, USA.
Fear of muscle toxicity remains a major reason that patients with
hyperlipidemia are undertreated. Recent evaluations of statin-induced
rhabdomyolysis offer new insights on the clinical management of both
muscle symptoms and hyperlipidemia after rhabdomyolysis. The incidence
of statin-induced rhabdomyolysis is higher in practice than in
controlled trials in which high-risk subjects are excluded. Accepted
risks include age; renal, hepatic, and thyroid dysfunction; and
hypertriglyceridemia. New findings suggest that exercise, Asian race,
and perioperative status also may increase the risk of statin muscle
toxicity. The proposed causes and the relationship of drug levels to
statin rhabdomyolysis are briefly reviewed along with the problems with
the pharmacokinetic theory. Data suggesting that patients with certain
metabolic abnormalities are predisposed to statin rhabdomyolysis are
presented. The evaluation and treatment of patients' muscle symptoms
and hyperlipidemia after statin rhabdomyolysis are presented. Patients
whose symptoms are related to other disorders need to be identified.
Lipid management of those whose symptoms are statin-related is reviewed
including treatment suggestions.
Publication Types:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16623120&query_hl=2&itool=pubmed_docsum
1: Przegl Lek. 2005;62 Suppl 2:51-4.
Related Articles, Links
[Statins in patients with renal failure--the current therapeutic
status]
[Article in Polish]
Filipiak KJ, Zawadzka-Bysko M.
I Katedra i Klinika Kardiologii Akademii Medycznej w Warszawie.
krzysztof.filipiak@amwaw.edu.pl
Statins are the most frequently used lipid-lowering drugs in all
cardiovascular disease. It has been postulated that also patients with
renal failure and end-stage renal disease (ESRD) may benefit from
statin therapy. Moreover, statins may exhibit additional inhibitory
effects on the atherogenesis, such as a modulation of the immune system
as triggered by oxidatively modified LDL and a reduction of the
inflammatory marker C-reactive protein (CRP). Statins reduce
inflammation, cell proliferation, which leads to a reduction in
cellular damage. Those effects are probably independent of cholesterol
levels. Limited data suggest that HMG-CoA reductase inhibitors
(statins) may slow loss of renal function in individuals with chronic
renal insufficiency. It is concluded on the basis of the CARE trial
that pravastatin may slow renal function loss in individuals with
moderate to severe kidney disease, especially those with proteinuria.
Similar data were obtained from recently published HPS trial with
simvastatin. These findings require confirmation by a large randomized
trial conducted specifically in people with chronic renal
insufficiency. Statins vary in their pharmacological profiles, leading
to distinct levels of systemic exposure and capacities to penetrate
skeletal myocytes. Pharmacokinetic interactions with certain agents
increase the likelihood of statin-induced myopathy and, in exceedingly
rare instances, potentially fatal rhabdomyolysis with myoglobinuria and
renal failure, therefore two statins have been suggested for renal
failure patients. These are the ones that are not metabolised by the
cytochrome P450 3A4 system--fluvastatin and pravastatin. The article
summarizes the current therapeutic status of statin use in renal
failure patients.
PMID: 16623120 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16581337&query_hl=2&itool=pubmed_docsum
1: Am J Cardiol. 2006 Apr 17;97(8A):95C-97C. Epub 2006 Jan 30.
Related Articles, Links
Â
Benefit versus risk in statin treatment.
Guyton JR.
Duke University Medical Center, Durham, North Carolina 27710, USA.
john.guyton@duke.edu
The Statin Safety Assessment Conference of the National Lipid
Association (NLA), reported in this supplement to The American Journal
of Cardiology, provides a comprehensive evaluation of old and new
experience on adverse events associated with the
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors,
or statins. To place these in context, one can express both the risk of
side effects and the benefits for cardiovascular disease in terms of
events per person-year of statin treatment. The mortality risk from
fatal rhabdomyolysis is approximately 0.3 per 100,000 person-years, and
the risks of nonfatal rhabdomyolysis and of putative
statin-attributable peripheral neuropathy are approximately 3 and 12
events, respectively, per 100,000 person-years. Reports of acute liver
failure and acute or chronic kidney disease give lower rate estimates
that, even when corrected for underreporting, are approximately equal
to the background rates of these conditions in the general population,
lending scant support for statin-attributable etiology. In contrast,
the benefit of statin use is to avert several hundred deaths and
several hundred cases each of heart and brain infarction per 100,000
person-years in appropriately treated high-risk patients. Although
population estimates such as these are useful, they must be translated
repeatedly to individual patient-provider encounters, where clinical
skill and art must combine with scientific evidence. The continued
publication of individual case reports and small randomized trials
among groups of patients with potential side effects should be
encouraged. Statins should not be used in situations where minimal
benefit is expected, as safety data and risk-benefit analysis must be
meshed with guidelines that help the clinician decide whom to treat and
how aggressively to treat.
PMID: 16581337 [PubMed - in process] |
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Jason
medicine forum Guru
Joined: 29 Apr 2005
Posts: 1120
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| Posted: Thu Jun 01, 2006 11:51 pm Post subject:
Re: Statins and Low-Grade Myopathy
|
|
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In article
<not-to-here-williamwag-745925.13092901062006@sn-indi.vsrv-sjc.supernews.net>,
William Wagner <not-to-here-williamwag@gmail.com> wrote:
In article
<jason-0106060959230001@66-52-22-15.lsan.pw-dia.impulse.net>,
jason@nospam.com (Jason Johnson) wrote:
| Quote: | In article <1149175772.834853.94160@i39g2000cwa.googlegroups.com>, "eml"
mmlevy46@hotmail.com> wrote:
Jason Johnson wrote:
Statins and Low-Grade Myopathy
In clinical trials and in clinical practice, statins have proved
to be remarkably safe.
The one notable side effect of statin therapy is myopathy.
A small fraction of patients who are treated with
statins will develop severe myopathy
eml wrote:
the following is from an unbiased clinician (has not made his
reputation on statins, does not research statins, nor is he funded by
the statin industry):
Underappreciated Statin-Induced Myopathic Weakness Causes Disability
Bruce H. Dobkin
University of California Los Angeles, Reed Neurologic Research Center,
bdobkin@mednet.ucla.edu
Introduction. Myopathic syndromes induced by 3-hydroxy-3-methylglutaryl
coenzyme A (HMG-CoA) reductase inhibitors (statins) include muscle
complaints, myalgia, myositis, and rhabdomyolysis. No prospective study
of statins, however, included tests of strength, so the incidence of
weakness, with or without muscle symptoms and elevated enzymes, is
unknown, and perhaps overlooked. Methods. From a convenience sample of
patients referred to an outpatient neurorehabilitation clinic over the
course of 1 year, 8 patients with hemiparetic stroke and 10 patients
with other presumed neurologic diseases presented with new difficulty
walking by 3 to 12 months after starting one of 3 statins. They
reported no myalgias, exercise-induced aches, or weakness. Examination
revealed proximal paresis graded 4/5 on the unaffected side in the
hemiparetic patients and symmetrical bilateral proximal limb and neck
flexor weakness graded 4/5 in the others. They stood up with difficulty
and walked with bilateral hip drop and imbalance on turns. Results.
Laboratory tests did not reveal myositis or other causes for paresis.
No improvement in strength or mobility was found 6 weeks after
initiating resistance exercises. The statin agent was stopped. By 3
months off statin, all recovered 5/5 proximal strength. Walking
improved, and they arose from a chair without pushing off with their
arms. Discussion. Serial manual muscle testing after initiating a
statin may detect a reversible cause of disability. A genetic
predisposition to statin-induced myopathic proximal weakness with
normal creatine kinase is consistent with a continuum of previously
reported symptoms and signs but may be underappreciated.
(in the discussion, the author notes that while single-subject,
double-blinded statins vs placebo studies would make the causal
relationship between disabling myopathy more apparent, he notes
recurrences in his patients' symptoms when the investigator was unaware
that several of the subjects had been placed back on the statin by
their primary physicians. p. 261)
Thanks for your post. If possible, try to find a research report related
to Rhabdomyolyis. I found several research reports related to
Statin-Induced Myopathic but could not find any research reports related to
Statin-Induced Rhabdomyolysis.
I found this information in a research report I found in the Journal
of the American College of Cardiology (Vol. 40, No. 3,2002)
"...It is rare that patients treated with a statin exhibit severe
myositis.... In this setting, failure to discontinue drug therapy
can lead to rhabdomyoysis and acute renal necrosis..."
JAMA 1990 264:71-95
In other words, if any statin patients develop severe myositis (severe
muscle pain), they should see their doctors ASAP.
Jason
|
I did and my Cardio guy made a note of as did my PCP. A few times.
This for two years after being on lesser statins for about three.
Cardio guy increased my lipitor from 20 to 80 and it was not good for
me. Down hill real quick . Like I mention often measure your calfs!!
Bill who is off all Doc's and trying to get BP happy.
LDL 160 HDL 70 and throw in CABG.
I hate to say bad things about doctors since I have a lot of respect for
the doctors that I have met in my life. However, I will make an exception
in this case--the doctor that increased your lipitor from 20 mg to 80 mg
was a fool. I read WHAT YOU MUST KOW ABOUT STATIN DRUGS AND THEIR NATURAL
ALTERNATIVES by
Jay S. Cohen, M.D. and he made it very clear in that book that it is a
risk any time a dose that high is prescribed. He said that low dose
statins are much safer. Believe it or not, some people can not even handle
a low dose (20 mg or below). |
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