What are the implications as doctors place millions of patients on this
powerful, cholesterol-lowering statin drug?
By Jay S. Cohen, MD
1337 Camino Del Mar, Suite C
Del Mar, CA 92014
This article is reprinted from
Medication side effects are the #4 leading cause of death in the U.S. annually
(JAMA 1998). Yet, few people receive adequate information when medication
is prescribed. This website is dedicated to providing information to help
you and your doctor make informed, intelligent choices about medications
and natural alternatives to maximize the benefits and minimize the risks
of treatment. Note: MedicationSense.com is free of drug company or government
If 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.
Of 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
The 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 below).
Crestor 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.
Here 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.
The 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.
Why 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.
One 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
Serious 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.
A far 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 instead.
When 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.
Should 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 cholesterol levels.4.5
“Forward-thinking 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
Despite 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.
A CRP level below 1 is low-risk; 1-3 moderate-risk; above 3 high-risk.
Should 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 life-long statins.”7
An 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.
If 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
Is Crestor the Only Treatment for Elevated CRP?
No. There are many choices, pharmaceutical and natural. This section will
discuss statin therapy.
We have known for a decade that the effects of all statins are similar.
This means that all statins can reduce elevated CRP.
In 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.
Just 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 on LDL-cholesterol.”9
If 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.
Women taking hormone replacement therapy should be aware that the therapy
can increase CRP levels.10 Check with your doctor.
There 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 effect.
Vitamin 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.
Vitamin E, with its natural anti-inflammatory effects, might also help
reduce elevated CRP.
Omega-3 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.
A natural 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.
Jay S. Cohen M.D. is a nationally recognized expert on medications and
side effects. He is an adjunct associate professor of preventive medicine
and author of
What You Need to Know about Statin Drugs and Their Natural Alternatives (Square One Publishers 2005). Dr. Cohen provides consultations to people
across America who are interested in statin drugs or natural alternatives
for reducing elevated CRP or cholesterol, or who are interested in cardiovascular
health and methods of prevention.
“The purpose of this E-Letter is solely informational and educational.
The information herein should not be considered to be a substitute for
the direct medical advice of your doctor, nor is it meant to encourage
the diagnosis or treatment of any illness, disease, or other medical problem
by laypersons. If you are under a physician’s care for any condition,
he or she can advise you whether the information in this E-Letter is suitable
for you. Readers should not make any changes in drugs, doses, or any other
aspects of their medical treatment unless specifically directed to do
so by their own doctors.”
3. 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.
4. Ridker, PM, Rifai, N, Rose, L, et al. R. Comparison of C-reactive protein
and low-density lipoprotein cholesterol levels in the prediction of first
New England Journal of Medicine 2002;347:1557-1565.
5. Albert, MA, Glynn, RJ, Ridker, PM. Plasma concentration of C-reactive
protein and the calculated.
Framingham Coronary Heart Disease Risk Score. Circulation 2003;108(2):161?5.
6. Sinatra, S. Statins: grossly overprescribed for cholesterol and underprescribed
for internal inflammation.
The Sinatra Health Report, Sept. 2002;8:1.
7. West A. JUPITER: separating the solid clinical matter from the hot gas.
Holistic Primary Care, Winter 2008;9(4):1-2.
8. Crestor costs. Costco pharmacy, Dec. 20, 2008:www.costco.com.
9. Ravnskov, U. Is atherosclerosis caused by high cholesterol? QJM (Quarterly
Journal of Medicine) 2002;95:397-403.
10. 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.
11. Block, G, Jensen, C, Dietrich, M, et al. Plasma C-reactive protein
concentrations in active and passive smokers: influence of antioxidant
supplementation. Journal of the American College of Nutrition 2004;23:141-147.
12. Simopoulos, AP. Essential Fatty Acids in Health and Chronic Disease.
American Journal of Clinical Nutrition 1999;70(suppl):560S-569S.
13. Simopoulos, AP. The Mediterranean diets: What is so special about the
diet of Greece?
Journal of Nutrition 2001;131:3065S-3073S.