Statin Drugs
My LDL cholesterol is 111. My doctor offers a statin drug because the
Cholesterol Assessment and Treatment guidelines
say that LDL-cholesterol should be treated aggressively in diabetics, even
though they acknowledge that AModification of blood pressure and lipids in people with
diabetes, however, does not reduce CHD risk.@ (p. II -15). My cholesterol is 165, my triglycerides are
63, my ratios are good, my pulse barely gets off the peg on the treadmill ... but
I should be on a statin drug?
I have questions: what=s the possible benefit? And, what=s the risk?
Statins Work by Lowering C-Reactive Protein, Not By Lowering Cholesterol
The answer to the first question is
that statins reduce C-reactive protein, a marker for inflammation which is an Aemerging risk factor@ for CHD. Two studies in the New England Journal of
Medicine suggest the benefit of statins must come from this effect:
APatients who have low CRP levels after statin therapy have better clinical outcomes than those with higher CRP levels, regardless of the resultant level of LDL cholesterol. Strategies to lower cardiovascular risk with statins should include monitoring CRP as well as cholesterol.@ (Ridker PM et al, NEJM 2005 352(1):20‑28)
AFor patients with coronary artery
disease, the reduced rate of progression of atherosclerosis associated with
intensive statin treatment, as compared with moderate statin treatment, is significantly
related to greater reductions in the levels of both atherogenic lipoproteins
and CRP.@ (Nissen SE, NEJM 2005 352(1):29‑38)
So in the studies showing a
protective effect, such effect kicks in long before the cholesterol and
LDL-cholesterol levels change; and those in whom LDL-cholesterol is not a risk
factor also benefit. It’s plain that statin drugs protective effect cannot stem
from their effect on cholesterol or LDL-cholesterol, and must therefore come
from lowered C-reactive protein. But my C-reactive protein level is already
below the limits of measurement, so statins are unlikely to help me!
And the magnitude of the possible benefit?
Somewhere between 0.12% and 3.5% less absolute risk of death,
depending on which of 5 statin drug trials you put your faith in. This is usually quoted as 21% to 41% less relative
risk of death, which sounds so much more encouraging but is actually profoundly
misleading.
Lies, damned lies and statistics
Benjamin Disraeli
It works like this. In the Scandinavian Simvastatin
Survival Study, there were about 2,222 CHD patients with high cholesterol in
each of the experimental and control groups.
In the experimental group there were 111 deaths, compared with 189
deaths in the control group, which is 5% and 8.5% respectively, and the
difference between these figures can be said to be 41% (the relative
risk) or 3.5% (the absolute risk).
lex non curat de minimis
the law doesn=t
care about trifles
This is a trifling improvement. Consider that initially healthy women in the
Nurses Health Study who took vitamin E 200IU for two years had 41% less
relative risk of coronary disease (and 13% less relative risk of all cause
mortality than those with low intakes), which
is directly comparable with the statin drug figure. (Stampfer MJ et al, Vitamin E
consumption and the risk of coronary disease in women. NEJM 1993 328:1444-9).
And what=s the risk of side effects?
In Statin Drugs ‑ A Critical Review of
the Risk/Benefit Clinical Research, Dr Joel Kauffman writes:
Besides
cancer, the other side effects of statins listed were incomplete, and should
have included constipation, myalgia, myopathy, polyneuropathy, liver and kidney damage, congestive heart
failure and amnesia. Side‑effects are usually said to affect 2‑6%
of patients. In fact, a recent meta‑analysis noted side‑effects in
20% of patients above the placebo rate (65% vs. 45%), and no change whatever in
the all‑cause death rate for atorvastatin.
[Newman CB et al, Safety of Atorvastatin Derived from
Analysis of 44 Completed Trials in 9,416 Patients. Am J Cardiol 2003;92:670‑6.]
The PROSPER trial on pravastatin showed no change in
the all‑cause death rate, and increased cancer and stroke rates.
(Kauffman, JM, DrugIntel.com,
The meta-analysis Dr Kauffman refers
to is by a doctor who works for Pfizer Global Pharmaceuticals, and it=s wildly entertaining that the
study’s abstract
claims only 3 or 4% suffered side-effects, yet in a Table in the body of the
paper we find the incidence of one or more side‑effect was 67%
among statin-treated patients, compared to 45% in the Placebo group:
TABLE 3. All Completed Studies Data Grouping:
Overview of Safety, Comparing Atorvastatin With Other Statins and Placebo
Newman
CB (of Pfizer) et al, Am
J Cardiol 2003,
92(6):670-6
Usually, the incidence of
side-effects in the placebo group (45%) is subtracted from the incidence in the
drug group (67%) to arrive at the incidence of side effects of the drug
(22%). But the investigator arbitrarily
reclassified so many side-effects as Anot treatment-related@ so that the
incidence of side-effects magically became 3% for atorvastatin,
and 4% for other statin drugs. The true rate of the side-effects of statins
may approach 22% per year.
What are the side-effects of statin
drugs? Baycol
(cerivastatin) was pulled from the market in August,
2001, because of 31 deaths from rhabdomyolisis, which is kidney failure cause by massive
release of myoglobin from damaged muscles. However, individual doctors have reported the
incidence of myalgia
(muscle pain), cardiomyopathy
(a failing, enlarged heart), liver dysfunction
and memory
problems in up to 30% of those who take statins. The side-effects are likely caused by the
drug inhibiting HMG coenzyme A, which inhibits both cholesterol synthesis and coenzyme Q10 production. Less of this enzyme, which is required for
energy production within cells, probably causes the myalgia and
cardiomyopathy. A 22% incidence of side-effects in the first year is consistent with
prescribing doctors observations, and is profoundly disquieting because these
side-effects will likely increase with length of treatment.
So, let us reflect. In the West of Scotland primary prevention
trial, in which men with high cholesterol were given Pravastatin, the conclusion
was that:
… treating 1000 middle-aged men with hypercholesterolemia and no evidence of a previous myocardial infarction with pravastatin for five years will result in 14 fewer coronary angiograms, 8 fewer revascularization procedures, 20 fewer nonfatal myocardial infarctions, 7 fewer deaths from cardiovascular causes, and 2 fewer deaths from other causes than would be expected in the absence of treatment. (the WOSCOPS primary prevention trial)
This speaks of 51 fewer bad outcomes
over five years of treatment of 1000 men, an absolute risk reduction of 5.1%,
or 1% per year which was reported as a 31% reduction in relative risk. This introduces a new and fascinating number,
the Number
Needed to Treat, which supposedly helps make the discussion of risk more
understandable. In this case, the number
is 1/0.01, or 100 people. This means if I and 100 fellow citizens take
this stuff for a year, one of our lives will be saved!
In the 5-year Cholesterol and Recurrent
Events secondary prevention trial, “The frequency of … [a fatal coronary event
or a nonfatal myocardial infarction] was 10.2 percent in the Pravastatin group
and 13.2 percent in the placebo group, an absolute difference of 3 percentage
points and a 24 percent reduction in risk” (CARE trial) so that the Number Needed to Treat
is 1/0.06, or 154 people.
The world is flat
If 154 people must be treated to save
one life, it is the drug manufacturer who enjoys the house percentage! A Table of Numbers
Needed to Treat for various drugs indicates how woefully ineffective
statins actually are. In treating
arthritis with glucosamine, for example, the number
needed to treat is only 5, meaning one in five people experience benefit in 3
to 8 weeks, which is pretty good odds.
The magic number for treatment with nutrition is only 1.3 people! If I take the statin for the rest of my life,
twenty years, say, my risk of death is only reduced by 13%, but my risk of side
effects becomes 20 times 22%, or 440%, a statistical certainty! By now I’m thinking that cholesterol
treatment by statin drugs belongs in the book Extraordinary Popular
Delusions and the Madness of Crowds (Three Rivers Press, 1995):
Why do otherwise intelligent individuals form seething masses of idiocy when they engage in collective action? Why do financially sensible people jump lemming-like into hare-brained speculative frenzies – only to jump broker-like out of windows when their fantasies dissolve? We may think that the Great Crash of 1929, junk bonds of the '80s, and over-valued high-tech stocks of the '90s are peculiarly 20th century aberrations, but Mackay's classic – first published in 1841 – shows that the madness and confusion of crowds knows no limits, and has no temporal bounds. These are extraordinarily illuminating, and, unfortunately, entertaining tales of chicanery, greed and naivete. (from a review at Amazon.com)