Benefits and Serious Risks of the Statin Crestor
Jay S. Cohen, M.D
you read a newspaper or watched television news on December 10,
2008, you would have thought that Crestor, a cholesterol-lowering
statin medication, was a wonder drug.
course, a few years ago you would have thought the same thing after
the heavy news coverage for another powerful statin, Lipitor. Yet,
my analyses at MedicationSense (2005, 2006) revealed that the Lipitor
studies demonstrated limited benefits and worrisome adverse effects.
new Crestor study, which involved more than 17,000 subjects, examined
the drug's effectiveness in reducing elevated blood levels of C-reactive
protein (CRP), a marker for cardiovascular inflammation.1 It is
currently believed that increased levels of inflammation are associated
with a higher incidence of heart attacks and strokes (more on CRP
Study Results -- and What They Really Mean
The authors of the Crestor-CRP study reported that over the 1.9
years of the study, there was a 44% reduction in cardiac events
(defined as heart attack, stroke, severe angina, or cardiac death)
among the subjects taking Crestor versus those taking a placebo.
A 44% reduction sounds very impressive, but it is misleading.
on the actual numbers from the study. Over 2 years, 1.36% of subjects
in the placebo group experienced a cardiac event; 0.77% of subjects
in the Crestor group experienced an event. The difference was 0.59%.
That is, less than 1%, a tiny difference.
difference was so tiny that it will require 120 individuals with
elevated CRP to take Crestor every day for two years for just one
person to obtain benefit.2 Meanwhile, the other 119 individuals
taking and paying for Crestor for two years will obtain no protection
from a cardiovascular event.
would the results of the Crestor-CRP study be proclaimed so loudly
nationwide despite being so tiny? The Crestor-CRP study was underwritten
by AstraZeneca, the manufacturer of Crestor. We have seen previously
that the marketing departments of drug companies are masters at
obtaining maximum media coverage for their studies even if the results
are unimpressive. Wide exposure means increased sales and big profits.
media outlet took a critical stance. ABCNEWS.com boldly offered
a dissenting opinion. In "Doctor Urges Caution in Interpreting
New Findings on Cholesterol Drug," Dr. Nortin Hadler wrote,
"The benefit shown in this study is tiny, and if [the Crestor-CRP
study] were repeated, there might be no benefit at all. I never
leap to act on the basis of such small effects."3
Side Effects Downplayed
In Crestor-CRP, the drug displayed many of the common adverse effects
of other statin medications (Lipitor, Zocor, Pravachol, Mevacor,
Lescol). Typical side effects include abdominal pain, muscle pain,
serious muscle breakdown (rhabdomyolysis), renal disorders, and
liver disorders. More subjects in the Crestor group experienced
these side effects than subjects in the placebo group.
more serious adverse effect occurred with Crestor: 270 cases of
newly diagnosed diabetes were reported among Crestor users, and
216 cases were reported among placebo users. The 54 more cases of
diabetes in the Crestor group was a significant and worrisome finding.
Diabetes is one of the most destructive, life-shortening disorders
of our time. It also is a leading cause of heart attacks and strokes.
Imagine, taking Crestor to prevent a heart attack and getting diabetes
the FDA decides whether to approve a new drug, it makes it decision
based on whether the drug will produce significantly more benefit
than risk. If Crestor were being evaluated today for approval by
the FDA, I believe Crestor would not be approved because its use
in the Crestor-CRP study was associated with many new cases of diabetes.
I Be Tested for Elevated CRP?
Half of all cardiac deaths occur in people with normal cholesterol
levels, so other factors cleary are involved in the development
of cardiovascular disease. New studies suggest that an elevated
level of CRP may be as important an indicator of cardiac risk as
cardiologists suspect that internal inflammation is the root cause
of many diseases including those of the heart and blood vessels,"
states cardiologist Stephen Sinatra. "Studies have shown that
people with elevated CRP run two times the risk of dying from a
cardiovascular-related problem compared with those who have high
cholesterol levels. Combine a cholesterol burden with a markedly
elevated CRP and your risk of heart attack and stroke increases
by a factor of nine."6
this, experts still disagree on whether the entire population should
be tested for elevated CRP. I believe that anyone who has cardiovascular
disease or is at risk for it should be tested for elevated CRP.
Furthermore, I also encourage anyone interested in prevention to
have a CRP test.
level below 1 is low-risk; 1-3 moderate-risk; above 3 high-risk.
My Elevated CRP Be Treated?
If your CRP level is elevated, it should not be ignored. Yet this
does not mean that your doctor should immediately prescribe you
a statin. As Dr. James Ehrlich, a pioneer in cardiovascular disease
screening, said, an elevated CRP "is a call for more information,
not an invitation to take an automation-like approach to prescribing
elevated CRP indicates a higher than normal level of inflammation
in the body. Many medical conditions can produce inflammation. Your
doctor should examine you for signs of infection: teeth, sinuses,
bladder, ovaries or prostate. A recent cold or bout of the flu can
also elevate CRP. Inflammatory disorders such as rheumatoid arthritis
may cause an elevated CRP.
no other causes of infection are found, the elevated CRP likely
reflects cardiovascular inflammation. Should it be treated? Experts
differ on this, but in general I recommend treatment.
Crestor the Only Treatment for Elevated CRP?
No. There are many choices, pharmaceutical and natural. This section
will discuss statin therapy.
have known for a decade that the effects of all statins are similar.
This means that all statins can reduce elevated CRP.
the Crestor-CRP study, 20 mg of Crestor was used. This is a powerful
dose, and because Crestor is only available as a brand-need drug,
it is expensive. At a nationwide discount pharmacy, 100 pills of
20-mg Crestor costs $340. The cost over one year is approximately
$1360. Over 20 years, the cost of Crestor 20 mg per day is approximately
$27,000.8 An equally powerful dose, 80 mg, of Zocor is available
as a generic (simvastatin), and it costs about 90% less.
because the Crestor-CRP study used a powerful dose of Crestor does
not mean that only a powerful dose will reduce elevated CRP. Some
experts believe that it is not necessary to use the same strong
statin doses that doctors frequently prescribe to reduce cholesterol
levels. Elevated levels of CRP may not require such strong treatment.
According to Dr. Uve Ravnskov, "It may be wiser to search for
the lowest effective dose instead of the dose with maximal effect
you are prone to getting side effects with medications, or if you
simply want to reduce your risk of side effects, ask your doctor
about starting with the lowest dose of simvastatin. If this does
not adequately reduce your elevated CRP level, ask your doctor to
increase the dose gradually until you arrive at the amount that
works. With Zocor (simvastatin), the lowest dose is 10 mg.
Integrative doctors recommend a variety of natural approaches to
reduce elevated CRP. Because smoking increases CRP, the first step
for any smoker is to stop smoking. Being overweight increases CRP,
so weight loss is also important. Healthy eating and exercise can
also reduce CRP levels.
taking hormone replacement therapy should be aware that the therapy
can increase CRP levels.10 Check with your doctor.
are several natural supplements that have anti-inflammatory qualities.
Alternative doctors often include one, such as curcumin or ginger,
in their combination treatment for elevated CRP. Some alternative
doctors include aspirin because of its proven anti-inflammatory
C might also be included in the treatment of elevated CRP. A study
in the Journal of the American College of Nutrition demonstrated
that 515 mg/day of vitamin C reduced CRP 24%.11 In comparison, in
the Crestor-CRP study, Crestor reduced CRP levels by an average
up 37%. Vitamin C plus other therapies mentioned in this section
might rival or exceed this result.
E, with its natural anti-inflammatory effects, might also help reduce
fatty acids (fish oils) have proven anti-inflammatory effects. Studies
have shown that daily intake of omega-3 fatty acids reduce the risk
of cardiac death and also reduce the pain of rheumatoid arthritis.12,13
Fish oils should be a standard part of the treatment of elevated
CRP. Because fish oils and aspirin taken together can increase the
body's tendency for bleeding, check with your doctor before taking
these therapies together.
supplement with properties similar to prescription statins is red
yeast rice. This fermentation product contains small amounts of
several statin-like compounds. It works like a mild statin and,
like prescription statins, reduces vascular inflammation and elevated
CRP. Red yeast rice can also reduce cholesterol levels. Like prescription
statins, red yeast rice can cause adverse effects, but the risk
is low and, if side effects occur, they are usually milder than
with prescription statins.
2008, Jay S. Cohen, M.D. All rights reserved.
Ridker PM, Danielson E, Fonseca FAH, et al (for the JUPITER Study
Group). Rosuvastatin to prevent vascular events in men and women
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Hadler NM. Crestor, by Jove... or Not. Doctor urges caution in interpreting
new findings on cholesterol drug. ABC News, Nov. 10, 2008:http://abcnews.go.com.
Ridker, PM, Rifai, N, Rose, L, et al. R. Comparison of C-reactive
protein and low-density lipoprotein cholesterol levels in the prediction
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Albert, MA, Glynn, RJ, Ridker, PM. Plasma concentration of C-reactive
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Sinatra, S. Statins: grossly overprescribed for cholesterol and
underprescribed for internal inflammation. The Sinatra Health Report,
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Crestor costs. Costco pharmacy, Dec. 20, 2008:www.costco.com.
Ravnskov, U. Is atherosclerosis caused by high cholesterol? QJM
(Quarterly Journal of Medicine) 2002;95:397-403.
Walsh, BW, Paul, S, Wild RA, et al. The Effects of Hormone Replacement
Therapy and Raloxifene on C?Reactive Protein and Homocysteine in
Healthy Postmenopausal Women: A Randomized, Controlled Trial. Journal
of Clinical Endocrinology and Metabolism 2004;85:214?218.
Block, G, Jensen, C, Dietrich, M, et al. Plasma C-reactive protein
concentrations in active and passive smokers: influence of antioxidant
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Simopoulos, AP. Essential Fatty Acids in Health and Chronic Disease.
American Journal of Clinical Nutrition 1999;70(suppl):560S-569S.
Simopoulos, AP. The Mediterranean diets: What is so special about
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have my permission to copy and disseminate all or part of these
articles if it is clearly identified as the work of: Jay S. Cohen,
M.D., The Free Underground MedicationSense E-Newsletter, www.MedicationSense.com.
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