What type of stroke?

And the other?

One in 50...  And how many MILLIONS are taking statins?

I am one who has had life-altering, disabling side effects from
statins. Now, four years after BAYCOL recall I have yet to recover well
enough to work at my former profession (journalist: reporter, news
photograher) or work with any predicability more than about 15 hours a
MONTH. I also cannot command the very good hourly wage my exceptional
skills drew. I have lost language function; and my vision is very bad.
I have lived on my cashed in savings and pension, sold everything I own
but for a bed, 2 chairs, a computer, and an 18 year old car. I on about
$800 a month, of my own money, until I am eligible for a somewhat
smaller sum at 65. It takes ingenuity to live well on this.
Fortunately, I have that. I regularly take goods including food, from
dumpsters in my neighbourhood. What I can't use I sell to consignment
shops.

Here is a partial list of my ADVERSE EFFECTS on STATINS:

Pancreatitis, gall bladder disease, helicobactor pylori ulcer, myopathy
and rhabdomyolysis, tendon and ligament damage, worsening of a
pre-existing back condition (2 instrumented fusions), cognitive
damage--many people with similar have been MRId with lesions and
atrophy, aphasia, short term memory loss, working memory difficulty,
transient global amnesia, permanent vision damage. This is a list
compiled from known statin adverse effects. I've probably forgotten
something.

Dr. Golomb is the P.I. of the 5 year NIH funded Statin Study. She and
her team of researchers are investagating the ADVERSE EFFECTS of
statins. Dr. Golomb has had other very demanding considerations of
late. But we statin-injured know she will soon return with renewed
vigour to continue her work.

This is Dr. Golomb's website. Her researchers would love to hear from
you with your experience of statins. They have questionnaires they will
mail to you; and packages of information on how to deal with statin
side effects. They will, at your request, contact your doctors on your
behalf if they do not acknowledge your symptoms might be coming from
your statin. Golomb et al have done this for thousands of people from
all over the world, apart from her study participants. Including me.

STATIN STUDY website
contact information within
http://medicine.ucsd.edu/SES/index.htm

Dr. Beatrice Golomb's cv:
http://medicine.ucsd.edu/faculty/golomb/

   Statin Adverse Effects: Implications for the Elderly
   by Beatrice A. Golomb, M.D., Ph.D.

   Geriatric Times         May/June 2004         Vol. V         Issue 3

   Statins, or 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors
(e.g., atorvastatin [Lipitor], simvastatin [Zocor]), are among the
best-selling prescription drugs in the world and are widely viewed as
very safe and effective. Their benefits to coronary artery disease have
been copiously documented and are incontrovertible. In addition,
statins have been shown to benefit survival in a large study of
middle-aged men with, or at high risk for, heart disease (Scandinavian
Simvastatin Survival Study Group, 1994). Nonetheless, all drugs have
potential adverse reactions despite their potential benefits.
Understanding these risks is vitally important, particularly in elderly
patients in whom both risks and benefits differ relative to younger
patients.

   Evidence suggests the balance of benefits to risks may be less
favorable in the elderly: Cholesterol becomes a less potent predictor
of cardiovascular problems, and adverse reactions from drugs, including
statins, may become more prominent. While patients at high risk for
cardiovascular disease receive mortality benefit from statins in
studies predominating in middle-aged men (Scandinavian Simvastatin
Survival Study Group, 1994), no trend toward survival benefit is seen
in elderly patients at high risk for cardiovascular disease (Shepherd
et al., 2002). A less favorable risk-benefit profile may particularly
hold for patients older than 85, in whom benefits may be more
attenuated and risks more amplified (Weverling-Rijnsburger et al.,
1997). In fact, in this older group, higher cholesterol has been linked
observationally to improved survival. This paper will review a
selection of the risks and adverse effects of statins that have special
implications for elderly patients.

   Muscle Problems

   Muscle problems are the most common reported adverse effects of
statins, according to an observational database maintained by the
University of California at San Diego Statin Study group. Perhaps the
most feared adverse effect of statins is rhabdomyolysis--a condition in
which there is severe breakdown of muscle tissue that may be toxic to
the kidneys and result in kidney failure or death. The muscle breakdown
commonly leads to a strong elevation in blood levels of muscle enzyme
creatine kinase (CK). Creatine kinase levels often exceed 10 times the
upper limit of normal in cases of frank rhabdomyolysis. Fatal
rhabdomyolysis occurred with increased frequency with cerivastatin
(Baycol) when used at higher doses or in combination with gemfibrozil
(Lopid); cerivastatin was removed from the U.S. market in 2001.
Rhabdomyolysis occurs with all statins, although the actual frequency
of occurrence is quite low.

   Physicians are most familiar with rhabdomyolysis, and many suppose
that for muscle pain to be statin-associated, it must induce muscle
symptoms throughout the body coupled with elevation of CK levels.
However, this reflects only one manifestation of statin-associated
muscle symptoms. Some patients have only new focal pain or new fatigue,
and may have mild or no elevation in CK levels. In some instances these
symptoms progress to rhabdomyolysis--one reason to take these symptoms
seriously--but many times they do not.

   An important double-blind, crossover biopsy study showed that some
patients receiving statin therapy with non-CK-elevating muscle pain
have objectively documentable, partially reversible mitochondrial
myopathy (Phillips et al., 2002). Even in the absence of rhabdomyolysis
or CK elevation, major effects on function and quality of life may
occur (Golomb et al., 2003). It is important to note that in both our
experience and that of others, muscle symptoms precipitated by statins
may not in all cases completely recover; this is consistent with the
finding that, pathologically, the myopathy may not completely reverse.

   Adverse muscle problems from statins, in addition to
rhabdomyolysis, take a variety of forms (Table). Shortness of breath
sometimes accompanies statin-associated muscle problems. The
"respiratory exchange ratio"--the ratio of carbon dioxide exhaled per
oxygen inhaled--is altered in people with statin myotoxicity (Phillips
et al., 2004). Occasionally, shortness of breath is the predominant
symptom. Patients may experience marked shortness of breath that occurs
following initiation of statin therapy and is sustained while statins
are continued for which no etiology is identified on extensive
cardiopulmonary workup. These symptoms resolve completely with statin
discontinuation.

   Muscle problems associated with statins may be more common among
the elderly. In the 2002 American College of Cardiology/American Heart
Association/National Heart, Lung, and Blood Institute Clinical Advisory
on the Use and Safety of Statins, Pasternak et al. noted the following
factors that may increase the risk for statin-associated myopathy:

       * advanced age (especially >80 years, women > men);
       * small body frame and frailty;
       * multisystem disease;
       * multiple medications;
       * perioperative periods; and
       * concurrent use of certain medications.

   These factors are especially common among the elderly, which places
them at increased risk for development of muscle problems with statins.

   Muscle problems associated with statins may be more debilitating
among the elderly. When muscle problems occur, they may have more
impact on the elderly. Elderly patients more commonly have already
declined in muscle strength and function; and are often already on, or
perched near, the steep part of the curve relating muscle strength to
physical function, independence and the ability to perform activities
of daily living. Thus, the same amount or proportion of compromise in
muscle function may have a substantially more profound impact on
quality of life in elderly patients. In addition, reductions in
physical function, indexed by reductions in lower extremity function,
are linked to self-reported disability, hospitalizations, admissions to
nursing homes and mortality from all causes (Guralnik et al., 2000,
1995, 1994; Penninx et al., 2000). Reductions in lower extremity
function are associated with reduced physical activity (McDermott et
al., 2002), so that such patients may lose the protection that exercise
is reported to afford against a host of conditions.

   Cognitive Loss

   Cognitive problems also occur with statins and may also have more
impact in elderly patients. Two randomized trials that were designed to
assess cognitive effects of statins have shown worsening in cognitive
function (Muldoon et al., 2002, 2000). In addition, several case
reports (King et al., 2003, 2001; Orsi et al., 2001) and one large case
series (involving 60 patients) (Wagstaff et al., 2003) have reported
deleterious cognitive effects of statins on memory and cognitive
function.

   Although not expressly designed to assess cognition, results from
the Heart Protection Study (HPS) (Heart Protection Study Collaborative
Group, 2002) and PROSPER trial (Shepherd et al., 2002) did not show
that statin therapy had favorable or deleterious effects on cognitive
measures that were tested. Several factors may help to explain the
discrepancy between findings from these large and smaller trials
targeted at testing cognition. First, different measures of cognition
were used that may not have tapped the areas in which problems occur.
The telephone survey measure in the HPS, for instance, would not have
captured visuomotor coordination and processing speed, which the other
trials suggested may be particularly affected.

   Second, the large trials enrolled people at high risk for
cardiovascular disease who experience benefit from statins to nonfatal
stroke, which may lead to improvements in cognition that may help to
balance out harms to cognition from other mechanisms. Although there
are trends toward increases in fatal stroke with statins in most of the
large statin trials, those who have died cannot complete cognitive
surveys. The impact on total number of strokes was unaffected in the
PROSPER trial with its sole focus on the elderly population. In the
PROSPER trial, the number of reduced transient ischemic attacks and
nonfatal strokes was actually matched by a similar number of increased
fatal strokes.

   Finally, the HPS used what is termed an "active run-in." For six
weeks, participants considered for enrollment were placed on
simvastatin, and those who were not fully compliant were dropped from
the study. Participants who perceived problems on the drug, including
cognitive problems, may have dropped the study themselves or skipped
pills intentionally. In addition, participants who developed memory
problems may have had trouble remembering to take the pills even if
they did not recognize deterioration in cognitive function. This run-in
process may have excluded participants who developed cognitive problems
on the drug, selecting only those who did not experience problems. Over
one-third of those who were interested in enrolling were excluded
following this compliance run-in.

   Because statins reduce nonfatal stroke (and cognition is obviously
not measured in people who have experienced fatal stroke), benefits by
statins for cognitive function in those in whom a stroke was averted
might be expected. It must be emphasized that the randomized trial
evidence has, to date, uniformly failed to show cognitive benefits by
statins and has supported no effect or frank and significant harm to
cognitive function.

   Analogous to the case for muscle adverse effects, the impact of
cognitive adverse effects from statins, when they occur, may be more
profound in the elderly. Elderly patients have more commonly already
experienced some decline in cognitive function, and more commonly are
in a vulnerable range in which additional impairment can have an impact
on independence and safety. Indeed, a number of studies show that even
modest reductions in cognition in the elderly are linked to increased
mortality, even when the reductions remain within the nondemented
range, and even when other health factors have been controlled for
(Bassuk et al., 2000; Frisoni et al., 1999; Korten et al., 1999; Smits
et al., 1999). In this context, adverse cognitive effects must be taken
seriously not only for their intrinsic impact on quality of life, but
for their potentially weighty implications for mortality.

   Other Adverse Effects

   A large variety of other adverse effects have been reported with
statins, including (but not limited to) gastrointestinal and
neurological effects, psychiatric problems, immune effects (e.g.,
lupus-like syndrome), erectile dysfunction and gynecomastia (breast
enlargement in men), rash and skin problems, and sleep problems.

   Of particular note for the elderly population, the PROSPER trial
found a significant 25% increase in incident cancer in participants
over age 70 randomized to statin therapy versus placebo (Shepherd et
al., 2002). Because statins have been reported to cause cancer in
animals, the significant increase in cancer cannot be dismissed as
necessarily a fluke. While a similar increase has not been seen in
studies of statins in younger participants, older people have poorer
stores of the cancer-protecting antioxidant nutrients that low-density
lipoprotein cholesterol helps to transport to tissue (so that the
increase in risk may occur selectively in elderly). Even if the
fractional change in risk were similar, the elderly have a higher risk
of cancer, increasing the number of cancer events that would manifest.

   Low cholesterol is also linked to infection, including development
of postoperative infection (Leardi et al., 2000) and predicts mortality
and adverse outcomes in hospitalized patients (Crook et al., 1999).
While some of this could be due to illness causing lower cholesterol,
it may also be that low cholesterol contributes to illness; indeed,
animal studies suggest lipoproteins may serve to protect against
bacterial endotoxin-induced death (Read et al., 1993).

   Statins may produce irritability or short temper in some people, a
problem that occurs with statin therapy and resolves with its
discontinuation (Golomb et al., 2004). For elderly patients who depend
on others for assistance, irritability and its impact on the
relationship with caregivers may have special implications.

   Heart failure may also occur in patients taking statin therapy. In
some people, the myopathic effects of statins may impair heart pumping
function (Silver et al., 2003). However, in patients with reduced
pumping function due to coronary artery blockages, statins may help
heart pumping by improving blood flow to the heart (Node et al., 2003).
It depends on the person whether benefit or harm dominates with statin
therapy.

   Discussion

   Observational studies show that as age increases within the elderly
age range, high cholesterol flattens then reverses as a risk factor for
mortality (Weverling-Rijnsburger et al., 1997). Although it remains to
be fully clarified whether these findings have relevance to
cholesterol-lowering treatment, the exclusive major randomized trial of
statins conducted in the elderly does nothing to dispel a possible
causal association, as it did not show benefit of statins to survival.
The impact was completely neutral on mortality despite selecting for an
elderly population at only moderately older age and selecting for
particularly high risk of heart disease--the elderly group in whom
greater benefits and lower risks would be expected (Shepherd et al.,
2002). There are reasons for concern that still older people--those
elderly not selecting for high cardiac risk and those who are frailer
than clinical trials generally select--might fare less well. Caution
should be exercised in provision of statins as with all treatments in
elderly patients. Any time a patient develops a new problem or
worsening of an existing problem, the medication list should be
reviewed and a possible contribution by medications should be
considered. This principle is by no means confined to statins. It is
particularly true in elderly patients who may be on many medications
with interacting effects, and in whom ability to withstand adverse drug
reactions may be attenuated.

   Acknowledgement

   Dr. Golomb would like to thank Tram Dang for research assistance
and Janis Ritchie, R.N., for administrative assistance.

   Dr. Golomb is on the faculty of the department of medicine and
family and preventive medicine at the University of California, San
Diego. Her research focuses on the risks and benefits of medical
interventions.

   References

   Bassuk SS, Wypij D, Berkman LF (2000), Cognitive impairment and
mortality in the community-dwelling elderly. Am J Epidemiol
151(7):676-688.

   Crook MA, Velauthar U, Moran L, Griffiths W (1999),
Hypocholesterolaemia in a hospital population. Ann Clin Biochem 36(pt
5):613-616.

   Frisoni GB, Fratiglioni L, Fastbom J et al. (1999), Mortality in
nondemented subjects with cognitive impairment: the influence of
health-related factors. Am J Epidemiol 150(10):1031-1044.

   Golomb BA, Kane T, Dimsdale JA (2004), Severe irritability
associated with statin cholesterol-lowering drugs. QJM 97(4):229-235.

   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.

   Guralnik JM, Ferrucci L, Pieper CF et al. (2000), Lower extremity
function and subsequent disability: consistency across studies,
predictive models, and value of gait speed alone compared with the
short physical performance battery. J Gerontol A Biol Sci Med Sci
55(4):M221-M231.

   Guralnik JM, Ferrucci L, Simonsick EM et al. (1995),
Lower-extremity function in persons over the age of 70 years as a
predictor of subsequent disability. N Engl J Med 332(9):556-561 [see
comment].

   Guralnik JM, Simonsick EM, Ferrucci L et al. (1994), A short
physical performance battery assessing lower extremity function:
association with self-reported disability and prediction of mortality
and nursing home admission. J Gerontol 49(2):M85-M94.

   Heart Protection Study Collaborative Group (2002), MRC/BHF Heart
Protection Study of cholesterol lowering with simvastatin in 20,536
high-risk individuals: a randomised placebo-controlled trial. Lancet
360(9326):7-22 [see comments].

   King DS, Jones DW, Wofford MR et al. (2001), Cognitive impairment
associated with atorvastatin. Presented at the American College of
Clinical Pharmacy Spring Practice and Research Forum. Salt Lake City;
April 22-25.

   King DS, Wilburn AJ, Wofford MR et al. (2003), Cognitive impairment
associated with atorvastatin and simvastatin. Pharmacotherapy
23(12):1663-1667.

   Korten AE, Jorm AF, Jiao Z et al. (1999), Health, cognitive, and
psychosocial factors as predictors of mortality in an elderly community
sample. J Epidemiol Community Health 53(2):83-88.

   Leardi S, Altilia F, Delmonaco S et al. (2000), [Blood levels of
cholesterol and postoperative septic complications.] Ann Ital Chir
71(2):233-237.

   McDermott MM, Greenland P, Ferrucci L et al. (2002), Lower
extremity performance is associated with daily life physical activity
in individuals with and without peripheral arterial disease. J Am
Geriatr Soc 50(2):247-255.

   Muldoon MF, Barger SD, Ryan CM et al. (2000), Effects of lovastatin
on cognitive function and psychological well-being. Am J Med
108(7):538-546.

   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.

   Node K, Fujita M, Kitakaze M et al. (2003), Short-term statin
therapy improves cardiac function and symptoms in patients with
idiopathic dilated cardiomyopathy. [Published erratum Circulation
108(17):2170.] Circulation 108(7):839-843.

   Orsi A, Sherman O, Woldeselassie Z (2001), Simvastatin-associated
memory loss. Pharmacotherapy 21(6):767-769.

   Pasternak RC, Smith SC, Bairey-Merz CN et al. (2002), ACC/AHA/NHLBI
Clinical Advisory on the Use and Safety of Statins. Stroke
33(9):2337-2341 [see comment].

   Penninx BW, Ferrucci L, Leveille SG et al. (2000), Lower extremity
performance in nondisabled older persons as a predictor of subsequent
hospitalization. J Gerontol A Biol Sci Med Sci 55(11):M691-M697.

   Phillips PS, Haas RH, Bannykh S et al. (2002), Statin-associated
myopathy with normal creatine kinase levels. Ann Intern Med
137(7):581-585 [see comments].

   Phillips CT, Gray NL, Puhek LM et al. (2004), Basal respiratory
exchange ratio is altered with statin use in normals. J Am Cardio
43(suppl A):233a.

   Read TE, Harris HW, Grunfeld C et al. (1993), The protective effect
of serum lipoproteins against bacterial lipopolysaccharide. Eur Heart J
14(suppl K):125-129.

   Scandinavian Simvastatin Survival Study Group (1994), Randomised
trial of cholesterol lowering in 4444 patients with coronary heart
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344(8934):1383-1389.

   Shepherd J, Blauw GJ, Murphy MB et al. (2002), Pravastatin in
elderly individuals at risk of vascular disease (PROSPER): a randomised
controlled trial. Lancet 360(9346):1623-1630 [see comments].

   Silver MA, Langsjoen PH, Szabo S et al. (2003), Statin
cardiomyopathy? A potential role for coenzyme Q10 therapy for
statin-induced changes in diastolic LV performance: description of a
clinical protocol. Biofactors 18(1-4):125-127.

   Smits CH, Deeg DJ, Kriegsman DM, Schmand B (1999), Cognitive
functioning and health as determinants of mortality in an older
population. Am J Epidemiol 150(9):978-986.

   Wagstaff LR, Mitton MW, Arvik BM, Doraiswamy PM (2003),
Statin-associated memory loss: analysis of 60 case reports and review
of the literature. Pharmacotherapy 23(7):871-880.

   Weverling-Rijnsburger AW, Blauw GJ, Lagaay AM et al. (1997), Total
cholesterol and risk of mortality in the oldest old. [Published erratum
Lancet 351(9095):70.] Lancet 350(9085):1119-1123 [see comment].

the 33% figure you quote--is that relative risk benefit or absolute
risk benefit?  thanks

Per (PeteCresswell):

I should add that some time ago, I naively went on my own version of a
vegetarian diet - with no supervision.   I enjoyed the food and my HDL and LDL
numbers didn't change much - but my trigs went through the roof - as in from 169
to 452.

So competent supervision is definitely important.

Pete,
You mentioned having your gall bladder removed.

Were you having any muscle pain since starting on the Zocor?  Have you had
regular blood tests checking CK?

There are many reasons, I suppose, for having a gall bladder removed, but
the concern that spurred my question is this:

Of the people who suffered rhabdomyolysis, a potentially deadly adverse
effect of statins, their medical records all followed a progression of
adverse effects:
- Muscle pain, then
- gout, then
- gall bladder removal, then
- kidney and liver problems, then
- rhabdomyolysis.

For a Frequently Asked Questions (FAQ) on Statin Adverse Effects, see:

http://www.freewebs.com/stopped_our_statins/StatinFAQ_031305wTOCv4.pdf

Did I miss where you posted your numbers Pete? If you haven't will you
consider doing that please.
Zee

They are not inconsistent. I suspect you do believe that statins have serious
side effects and these are not being made public enough. I suspect the writer
of the original artical believes that people are not being sufficiently warned
about the dangers of stopping statins.

Bill