Advertising Passed Off As Research
Confuses the Public
Study Published in
New England
Journal of Medicine
Expands the Indications for Statins—and the Public Suffers
Today’s (November 10,
2008) front page headlines worldwide announced a simple test called
“highly sensitive C-reactive protein” (HS-CRP) and the most powerful
cholesterol-lowering statin currently on the market, Crestor (rosuvastatin),
used together, could cut the risk of heart attacks, strokes, and death
from cardiovascular disease in half.1 For the casual reader,
Crestor appears to be a miracle treatment with few risks and reasonable
costs. Today’s publication adds to the belief of a growing number of
experts that “statins are so wonderful that they should be added to our
drinking water” (like fluoride).
For this study nearly
90,000 people were examined, and most of them were identified as being
at increased risk for a heart attack, stroke, and/or premature death.
Rather than choosing professionalism and treating the underlying causes
of their health problems: their diet and lifestyle; these researchers
chose commercialism; creating the most effective pharmaceutical
advertising campaign ever devised. And they have succeeded.
The study was funded
by the maker of the drug, AstraZeneca, and the lead author, Paul M
Ridker MD, is listed as a co-inventor on patents held by Brigham and
Women's Hospital related to the use of HS-CRP for the evaluation of a
patient’s risk of heart disease.
Profits Are
Determining Medical Care
The cost of Crestor (rosuvastatin)
is about $3.45 per day—much higher than that of generic statins. That
amounts to $1259 a year just for this drug. Doing the math, this means
to prevent one event in one “apparently healthy patient” would cost
about $300,000 just for the Crestor. These figures do not include the
cost of doctors’ visits, the lab tests and the treatment of side effects
from the medications, including the serious adverse events caused by
Crestor.(Calculations: Absolute benefit of 1 event for 120 treated
patients for 1.9 years at $1259 = 120 x 1.9 x $1259 = $287,052.)
Heart attacks,
strokes, and the need for surgery and drugs are caused primarily by
eating the Western diet, and secondarily by “bad habits,” including
cigarette smoking and lack of exercise. The underlying disease,
atherosclerosis, is reversible. There are no side effects or added
costs with diet-therapy—therein lies the problem (no profit).
How Did They Get
Those Results?
1)
They stacked the deck with sick people, but passed them off as
“healthy” to the press and public. Previous studies of statins have
found that people at high risk for a heart attack or stroke will
benefit, but healthy people will not.2 The deception in this
study began by choosing high-risk test subjects and identifying them as
“apparently healthy men and women.”
The nearly 18,000
people selected for the study out of the original 89,890 screened had
very high HS-CRP levels of over 4.2 mg/L. Simply based on the HS-CRP
these were not “apparently healthy,” but rather, people at high risk for
cardiovascular disease. The cutoff value for high “bad” LDL-cholesterol
level was 130 mg/dL. This allowed the inclusion of many high-risk
people—“good health” is associated with a LDL below 100 mg/dL. In
addition, the average blood pressure (134/80 mmHg) and total cholesterol
(186 mg/dL) numbers were too high for these people to be considered
“apparently healthy.”
The baseline median
body mass index (BMI) was 28.3 (normal 18.5-24.9), indicating most of
these people were overweight or obese. At the beginning of the study 41%
were reported to have “metabolic syndrome.” (Metabolic syndrome is a
combination of medical disorders, such as abdominal obesity, elevated
blood sugar, triglycerides, and blood pressure, which considered
together indicate an increased risk of cardiovascular disease.)
2)
They Emphasized Relative, Not Absolute Benefits
Reporting the “relative benefit” of a drug is the most common method
used by drug companies to deceive patients and their doctors. In this
case relative risk reduction was determined by dividing the number of
designated events (heart attacks, stroke, and deaths from cardiovascular
disease) for the treated (Crestor) group by the events for the placebo
group: 83 vs. 157. This mean the treated group had half (53%) the chance
of an event compared to placebo. This figure is impressive.
However, the “absolute
benefit”—the real life benefit a person can expect from treatment—is a
very different story. Consider the numbers: nearly 18,000 people were
treated for almost 2 years. In absolute numbers this means 83/8901 or
0.9% of those people taking Crestor had a serious event, as opposed to
157/8901 or 1.8% of those in the placebo group. This is an absolute
event reduction of less than 1%. In other words, 120 patients had to be
treated with Crestor for 1.9 years to prevent one designated event:
heart attacks, strokes, and death from cardiovascular disease.
3)
Early Termination of the Study Is Impressive but Suggests Dishonesty.
The study was supposed to go on for 4 years, but was stopped at 1.9
years for “ethical reasons.” It was considered unethical to continue the
study because continuation would mean depriving the people in the
placebo group of the advantage of the treatment—Crestor in this case.
“Early termination” of research is a powerful technique used by
pharmaceutical companies to enhance the perceived value of the treatment
in the minds of the medical profession, the press, and the public. But
it has been shown that studies that are stopped early are biased and
prone to exaggeration.3 According to a recent review in the
Journal of the American Medical Association, “RCTs (Randomized
Controlled Trials) stopped early for benefit are becoming
more common, often fail to adequately report relevant information
about the decision to stop early, and show implausibly large
treatment effects, particularly when the number of events is
small. These findings suggest clinicians should view the results
of
such trials with skepticism.”4
No mention was made in
this report about two other recent studies (CORONA and GISSI-HF) where
Crestor did not result in any improvement in survival.5,6
4) Researchers
Underemphasized Serious Adverse Events from Crestor
One of the most
important findings from this study (found in table 4) is the similar
number of serious adverse events in both the Crestor-treated and placebo
groups—1352 (15.2%) vs. 1377 (15.5%). How can that be? Wasn’t the
number of events about half (83 vs. 157) for those taking Crestor? The
study focused on events (heart attacks, strokes, and deaths from
cardiovascular disease) that are expected to respond favorably to
treatment. The study, and the media that followed, did not give
appropriate attention to all adverse events that occurred. Clearly,
there was an increase in non-cardiac serious adverse events in the
Crestor group. Obviously, it is not in the best interest of the sponsor
of the study to give attention to this finding.
The article did
mention an increase in risk of diabetes in those treated with Crestor
(270 reports of diabetes, vs. 216 in the placebo group). But there must
be more. Amazingly, this study reported only one case of serious muscle
damage (rhabdomyolysis). The expected rate is 3.16 fatal cases per
million prescriptions written for Crestor.7 This is 16 to 80
times higher than that reported for other statins. Almost four years ago
Dr. David Graham, FDA's associate director for science and medicine,
named Crestor as one of five drugs that pose serious safety concerns and
the FDA told AstraZeneca to pull its ads for Crestor because they do not
mention its risks of causing acute kidney failure or rhabdomyolysis.
There is no long-term
information on the safety of using these high doses of Crestor to lower
“bad” LDL-cholesterol to 55 mg/dL (as they did in this study). This
study was stopped after less than 2 years, but patients prescribed
statins can expect to take them for 20 years and longer.
One More
Deregulated System That Must Be Fixed
Neither the patient
nor our over-burdened health care system can thrive with this kind of
deception from the pharmaceutical companies and the medical journals.
Fortunately, health care professionals are
beginning to recognize that what is happening in medical care
is just like the tragedies we have recently witnessed in the stock
market and the housing industries. Unregulated business practices lead
to a few very rich people becoming even richer, and severe suffering for
the rest of us. The time has come for change. Researchers and
publishers must be held accountable like stockbrokers and bankers.
Regulation enacted to protect the public is long overdue.
What is
HS-CRP?
C-reactive
protein (CRP) is a molecule produced in response to
inflammation. It is non-specific, in other words, it does
not identify the source of the inflammation, which could be
due to an infection of a toe, arthritis, or a bad cold. The
connection to cardiovascular disease (heart attacks and
strokes) is that the sores (like pustules) on the artery
walls cause the CRP to rise. This festering artery disease
(atherosclerosis) is the underlying cause of heart attacks
and strokes. The elevated CRP is simply one sign of the
trouble—other signs are elevated blood pressure, blood
sugar, cholesterol and triglycerides.
Highly
sensitive (HS) refers to laboratory methodology used to
increase accuracy. A level of less than 1mg/L indicates low
risk, a level between 1 and 3mg/L indicates moderate risk,
and a level greater than 3mg/L indicates high risk of active
artery disease.
The people in this study were on average
in the high-risk group, in need of immediate and intensive
dietary intervention.
Statins,
like Crestor, are believed to be anti-inflammatory, reducing
HS-CRP levels. Even without the postulated benefit of
reduced inflammation, the cholesterol lowering effects of
statins have been shown to reduce the risk of serious
cardiovascular events in people at high risk.2 A
low-fat diet also cuts CRP in half in 4 weeks.8
This reflects less inflammation, which means healing the
arteries as a result of following a healthier diet. |
References:
1) Ridker,P Danielson, E Fonseca F, Genest J, Gotto A,
Kastelein J, Koenig W, Libby P, Lorenzatti A, MacFadyen J, Nordestgaard
B, Shepherd J, Willerson J, Glynn R, the JUPITER Study Group.
Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated
C-Reactive Protein. N Engl J Med. 2008; 359:2195-2207
2) Abramson J, Wright JM. Are lipid-lowering guidelines
evidence-based? Lancet. 2007 Jan 20;369(9557):168-9.
3) Hopewell S, Clarke M, Moher D, Wager E, Middleton P,
et al.
PLoS Medicine
Vol. 5, No. 1, e20 doi:10.1371/journal.pmed.0050020
4) Montori VM, Devereaux PJ, Adhikari NK, Burns KE,
Eggert CH, Briel M, Lacchetti C, Leung TW, Darling E, Bryant DM, Bucher
HC, Schünemann HJ, Meade MO, Cook DJ, Erwin PJ, Sood A, Sood R, Lo B,
Thompson CA, Zhou Q, Mills E, Guyatt GH. Randomized trials stopped early
for benefit: a systematic review. JAMA. 2005 Nov
2;294(17):2203-9.
5) Kjekshus J, Apetrei E, Barrios V, Böhm M, Cleland JG,
Cornel JH, Dunselman P, Fonseca C, Goudev A, Grande P, Gullestad L,
Hjalmarson A, Hradec J, Jánosi A, Kamensk? G, Komajda M, Korewicki J,
Kuusi T, Mach F, Mareev V, McMurray JJ, Ranjith N, Schaufelberger M,
Vanhaecke J, van Veldhuisen DJ, Waagstein F, Wedel H, Wikstrand J;
CORONA Group. Rosuvastatin in older patients with systolic heart
failure. N Engl J Med. 2007 Nov 29;357(22):2248-61.
6) Gissi-Hf Investigators. Effect of rosuvastatin in
patients with chronic heart failure (the GISSI-HF trial): a randomised,
double-blind, placebo-controlled trial. Lancet. 2008 Aug 29.
7) Bruce J, Rabkin E., Martin V. Rhabdomyolysis
associated with current us of simvastatin and Nefazodone: Case report
and current review of the literature. Advanced Studies in Medicine
2003; 3: 168-172.
8)Rankin JW, Turpyn AD. Low carbohydrate, high fat diet
increases C-reactive protein during weight loss. J Am Coll Nutr.
2007 Apr;26(2):163-9. |