Over Dose: Jay Cohen on statins and marketing hype

From: Zee (zwalanga_at_yahoo.com)
Date: 07/09/04 

Date: 9 Jul 2004 12:13:58 -0700

"Pharmaceutical companies are waging aggressive campaigns to change
prescribers' habits and to distinguish their products from competing
ones, even when products are virtually indistinguishable. Victory in
these therapeutic-class wars can mean millions [billions today] of
dollars for a drug company. But for patients and providers it can mean
misleading promotions, conflicts of interest, increased costs for
health care, and ultimately, inappropriate prescribing.18"

From: http://www.medicationsense.com/index.html

THE TRUTH ABOUT CRESTOR: IS CRESTOR DANGEROUS AND, IF SO, WHY? The
Intensive Marketing of This New, Super-Strong, Cholesterol-Lowering
Statin Drug Raises Questions and Concerns. Are Crestor Users in
Jeopardy? Is Crestor Especially Dangerous for Asians? Who Should Take
Crestor and When? A Lower, Safer Approach That Most Doctors and
Patients Don't Know About.

What is Crestor and What Is the Problem?

Crestor is the newest statin and the strongest statin yet. Statins are
the highly touted drugs for reducing cholesterol. Studies clearly show
that statins improve cholesterol numbers (by lowering LDL and raising
HDL) and may reduce C-reactive protein. Statins impede
atherosclerosis, reduce heart attacks and strokes, and cardiac death.
Thus, the statins Lipitor and Zocor are not only the #1 and #2
top-selling drugs in America, but also household names.

Other statins include Pravachol, Mevacor, and Lescol -- and now
ultra-potent Crestor. Until 2001, there was another statin: Baycol. It
was then the newest statin and a potent statin -- until it was
withdrawn because of dozens of deaths. Is Crestor another Lipitor or
another Baycol? Although Crestor has been on the market only a year,
it has already been linked to numerous cases of severe muscle
breakdown, kidney toxicity, and deaths. Public Citizen recently
petitioned the FDA to ban Crestor.

The Marketing of Super-Strong Crestor
Crestor's introduction in August 2003 provides a textbook example of
how marketing strategies can supersede medical science and common
sense. Taking a page from Lipitor's highly successful marketing
campaign in 1997, Crestor is now being aggressively marketed as the
strongest statin of all.

The manufacturer's recommended initial dose of Crestor is 10 mg/day
(except for people with kidney problems). This dosage is so strong
that Crestor's advertising can boast it is stronger than equivalent
doses of any other statin. This is quite a claim, because Lipitor and
Zocor are pretty strong themselves. Indeed, their top-selling status
has been built on their own advertising about their power to reduce
cholesterol and LDL-cholesterol (LDL-C) levels.

But more isn't necessarily better with most medications, including
statins. As I've written in medical journal articles and in my
upcoming book (What You Need To Know About Statin Drugs And Their
Natural Alternatives),1 the standard starting doses of Lipitor and
Zocor are often double or quadruple the amounts that millions of
people actually need, triggering many avoidable side effects. So what
can we say about super-strong Crestor, which is even stronger? We can
say that the drug company-recommended, super-strong initial 10-mg dose
of Crestor has already been linked to severe toxicities.1A This should
not surprise anyone.

Excessive Doses = More Side Effects
One of my basic principles is: The best dose of any medication is the
least amount that works. Medical science agrees. Most people with
elevated cholesterol or LDL-C have mild-to-moderate elevations. For
many, dietary interventions are enough. For others, modest statin
doses are often plenty. But the recommended initial doses of Lipitor,
Zocor, and Pravachol are strong, yet that's what doctors prescribe to
most people, even to people who don't need such strong statin therapy.
This is the crux of the problem of statin side effects such as muscle
aches, joint pains, abdominal discomfort, memory and cognitive
impairment.2-6 Side effects are a major reason that 60%-75% of people
started on statins quit treatment.7,8 The average time until they
discontinue treatment: 8 months. Many people quit within a few months.

Liver injury, liver toxicity, and death are also concerns with
statins. Like other statin side effects, these reactions are
dose-related: the greater the dose, the greater the risk. Dr. W.C.
Roberts, the editor-in-chief of the American Journal of Cardiology,
warns: "With each doubling of the [statin] dose, the frequency of
liver enzyme elevations [indicating liver irritation or injury] also
doubles.9"

Nerve injuries have now been documented in people taking statins
long-term.10, 11 The incidence is low, perhaps 1 in 2000 to 5,000, but
with millions taking statins, this adverse effect will afflict
thousands of people each year. These injuries can be severe and
permanent, and even mild nerve injuries can take months to fade away.

Doctors cannot anticipate who will develop a long-term side effect
with statins, but doctors should (but usually don't) anticipate that
they will occur in some people. The only defense: using the least
amount of medication you need.

Do We Need a Stronger Statin?
The standard starting dose of Crestor is 10 mg, which reduces LDL-C a
whopping 46%-52%.12 Some people, especially those with serious
coronary disease, require this degree of LDL-C reduction, but most
people with elevated cholesterol require only 20%-30% reductions --
and therefore much less medication.

Crestor's manufacturer does recommend a lower 5-mg dose for people
requiring "less aggressive LDL-C reductions.12" Yet, 5-mg Crestor
reduces LDL-C 42%, still far more than most people with elevated
cholesterol need.

And remember, this 42% LDL-C reduction represents the average among
study subjects. Many people get even greater reductions with this
dosage. In one study, 5 mg of Crestor reduced LDL-C as much as 71% in
subjects.13 This is an impressive number, but reducing cholesterol too
aggressively is believed to be a trigger for cognitive, memory, and
mood problems with statins. And too low cholesterol levels aren't good
either, because cholesterol is a necessary building block in human
cells and a substrate of many of our hormones.

So contrary to Crestor's marketing, we shouldn't be overly impressed
with which statin is strongest. You don't want the strongest statin.
You want the mildest statin that works for you.

Lower, Safer Doses of Crestor Work --
But Your Doctor Doesn't Know About Them
The lowest marketed dose of Crestor is 5 mg. Yet, studies show that
2.5 mg of Crestor reduces LDL-C 40%, and just 1 mg reduces LDL-C 34%,
on average.13, 14 These doses are still stronger than the standard
initial doses of Pravachol, Mevacor, Zocor, and Lescol, and they would
certainly be strong enough for most people with elevated cholesterol.
Indeed, the lead author of one Crestor study stated: "Even at 1
mg/day, rosuvastatin [Crestor] reduced LDL-C by 35%, the same
percentage reduction seen with simvastatin [Zocor] 20 and 40 mg.14"

Yet, you won't find any information about this in the Crestor package
insert,12 pharmacy slips, or the Physicians' Desk Reference.2
Crestor's manufacturer isn't going to inform you or your doctor about
lower Crestor doses that aren't available, even if they are effective
-- and safer. This goes right to the heart of the issue of informed
consent. Your right of informed consent is denied if you aren't given
enough information to make an intelligent choice.15 You aren't alone:
one study showed that only 9% of office patients receive enough
information to fulfill their right of informed consent .16 No wonder
medication side effects continue to be one of the leading causes of
death in America.

The Marketing of Crestor
Why isn't Crestor marketed at lower, safer doses? Drug companies like
to keep dosing simple, because simple dosing makes doctors' job
easier. The fact is, doctors are inadequately trained about
medications. Their one pharmacology course covers hundreds upon
hundreds of drugs, but not deeply. Doctors assume that drug companies
and the FDA are providing complete information with the best doses,
when in fact they aren't. That's why doctors rarely question
irrational drug company guidelines even when the guidelines tell
doctors to prescribe the same strong doses to young and old, big and
small, healthy and frail.

I could list hundreds of quotes about problems with drug research and
marketing, but the following two will suffice. The first is from Dr.
Andrew Herxheimer, the highly respected expert at Britain's renowned
Cochrane Coalition:

"Drugs are often introduced at a dose that will be effective in around
90% of the target population, because this helps market penetration.
The 25% of patients who are most sensitive to the drug get much more
than they need.17"

Actually, with statins, the number is probably much higher. Dr. David
Kessler, when he was FDA commissioner, wrote this about marketing
strategies vs. medical science:

"Pharmaceutical companies are waging aggressive campaigns to change
prescribers' habits and to distinguish their products from competing
ones, even when products are virtually indistinguishable. Victory in
these therapeutic-class wars can mean millions [billions today] of
dollars for a drug company. But for patients and providers it can mean
misleading promotions, conflicts of interest, increased costs for
health care, and ultimately, inappropriate prescribing.18"

My articles and books contain dozens of examples of excessively dosed
drugs. Crestor is another. In October 2003, Dr. Richard Horton, editor
of the British Medical Journal, published a scathing critique of
Crestor's marketing, stating that the manufacturer's tactics "raise
disturbing questions about how drugs enter clinical practice and what
measures exist to protect patients from inadequately investigated
medicines...." Yet, Horton added, the manufacturer will "do whatever
it takes to persuade doctors to prescribe rosuvastatin, including
launching an estimated $1 billion first-year promotional campaign.19"

So, even though the FDA has repeatedly cautioned doctors about using
new drugs when older, better known drugs are available, the onslaught
of drug reps and intensive advertising pushing Crestor has worked. By
early 2004, 27% of all new prescriptions for statin drugs was for
Crestor. The Wall Street Journal reported:

"AstraZeneca sales force (Crestor) was making more calls to doctors
than any of its competitors. Beginning in late February, reflecting
the sales calls, new prescriptions of Crestor began to rise and
overtook Lipitor by the beginning of March.20"

Once again, intensive marketing trumps medical science -- and patient
safety. Is this how we want our health care system to run?

Is Crestor Risky for Asians?
In studies, blood levels of Crestor rose twice as high in Chinese and
Japanese subjects as in other groups. Higher blood levels mean
stronger effects and greater risks of side effects. The only place in
the lengthy Crestor package insert that specifically describes this
problem is the "Clinical Pharmacology, Special Populations" section,
which many doctors won't notice. Yet, the all-important "Dosage and
Administration" section, which most doctors do read, makes no mention
of Asian patients. It does make a vague statement about patients "who
have predisposing factors" to side effects, but many doctors will miss
the implication and prescribe the same strong standard doses of
Crestor to Asian patients. If you are of Asian heritage, it is better
to use other statins that don't pose particular risks to Asians.

Who Needs Crestor? Crestor vs. Lipitor, Zocor, Pravachol, Mevacor, and
Lescol
How does Crestor compare with other statins? Who should get Crestor?
As it is, many doctors are already prescribing overly strong doses of
statins to people who don't need such intensive treatment. Stories
abound about doctors prescribing excessively strong doses and ignoring
obvious, serious side effects.

It is important to remember that in most instances, elevated
cholesterol is not an emergency. There's time to use caution, to use
the "Start Low, Go Slow" method that allows you and your doctor to
gauge the exact amount of medication you need. Different people get
widely differing responses to statins. Some people get large LDL-C
reductions with tiny doses. Others require stronger doses. The only
way to know your response is to start low and, if needed, increase
gradually. Of all the statins, this is least possible with Crestor.

Who actually needs Crestor? Hardly anyone. Other statins have much
longer track records and should be used first. The respected Medical
Letter on Drugs and Therapeutics agrees, recommending Crestor only for
"non-Asian patients who have not responded adequately to statins with
a longer record.21"

The fact is, milder statins such as Mevacor, Lescol, and Pravachol are
strong enough for most people. Lipitor and Zocor are strong enough for
almost all of the rest. There are very few people who actually require
super-strong Crestor. Moreover, Mevacor is now available as generic
lovastatin and much cheaper at pharmacies such as Costco.

What You Should Do?
A favorite tactic of drug companies is to provide free samples. Drug
companies know that once you are started on a medication, you won't
want to switch. So sales reps shower doctors with samples, and doctors
think they are doing you a favor by giving you a free sample when
starting a medication. But they aren't doing you a favor at all.

So if your doctor offers you free samples of Crestor, respectfully
decline. Drug companies don't provide samples because of their
altruism, but as hooks to boost sales of new drugs against established
competitors. Unless a new drug really offers something important,
resist the pitch.

When Baycol was withdrawn because of dozens of deaths, Newsweek asked
me what I thought. My response: "I think it's frightening that 800,000
people were taking Baycol. Baycol was the newest and least known
statin, and it offered nothing superior to other statins. No one
should have been exposed to Baycol unless the other five statins had
been tried first unsuccessfully, and that is very few people.22" My
opinion remains exactly the same about Crestor.

The marketing of Crestor is an outrage. The frequent prescribing of
super-strong Crestor by doctors is symptomatic of how dominant the
drug industry is in influencing the knowledge and decisions of
doctors. We must change this. If your doctor suggests Crestor, ask
why. Unless there's a very good reason, tell your doctor you would
prefer a statin with a longer track record. If your doctor dismisses
your opinion, you can quote the top drug experts at the FDA, as they
recently wrote in the Journal of the American Medical Association:

"Clearly, physicians and patients should be aware that recently
marketed drugs are at risk of being found to cause unsuspected serious
adverse effects.... A physician considering prescribing a new drug
should consider carefully the reason for the choice, particularly when
an equally effective alternative is available, as there is always some
risk of an undiscovered adverse drug reaction.23"

If you are feeling bold, ask your doctor why he/she is suggesting the
least-known, most-powerful statin that already has been linked to
multiple toxicities, rather than better known, apparently safer other
statins. Until we hold our own doctors accountable for their
thoughtless decisions, nothing will change and our children will be
subjected to the same drug-company controlled health care system.

You may also want to tell your doctor that you would rather start with
a low-dose statin. Many people get good results with low doses. If you
don't, the dosage can be easily, gradually increased so that you get
the right amount of statin for you and not a milligram more. Remember,
the best dose of any medication is the lowest dose that works. If the
medical community applied this principle consistently, we would not
have a side-effect epidemic today.

REFERENCES
1. Cohen, JS. What You Need to Know about Statin Drugs and Their
Natural Alternatives. Square One Publishing, New York: September 2004.
1A. More Crestor Safety Concern; Call for Ban Renewed. Dickinson's FDA
Webview, 5/17/2004.
2. Physicians' Desk Reference, 57th Edition, Montvale, N.J.: Medical
Economics Company, 2003.
3. Wierzbicki, AS, Lumb, PJ, Semra, et al. Atorvastatin compared with
simvastatin-based therapies in the management of severe familial
hyperlipidaemias. Qjm 1999;92(7):387-94.
4. Nawrocki, JW, Weiss, SR, Davidson, MH, et al. Reduction of LDL
cholesterol by 25% to 60% in patients with primary
hypercholesterolemia by atorvastatin, a new HMG-CoA reductase
inhibitor. Arteriosclerosis, Thrombosis, and Vascular Biology
1995;15(5):678-82.
5. Bertolini, S, Bon, GB, Campbell, LM, et al. Efficacy and safety of
atorvastatin compared to pravastatin in patients with
hypercholesterolemia. Atherosclerosis 1997;130(1-2):191-7.
6. Marz W, Wollschlager H, Klein G, et al. Safety of low-density
lipoprotein cholestrol reduction with atorvastatin versus simvastatin
in a coronary heart disease population (the TARGET TANGIBLE trial).
American Journal of Cardiology 1999;84(1):7-13.
7. Jackevicius, CA, Mamdani, M, Tu, JV. Adherence with statin therapy
in elderly patients with and without acute coronary syndromes. JAMA
2002;288:462-467.
8. Benner, JS, Glynn, RJ, Mogun, H, et al. Long-term persistence in
use of statin therapy in elderly patients. JAMA 2002;288:455-461.
9. Roberts, WC. The rule of 5 and the rule of 7 in lipid-lowering by
statin drugs. American Journal of Cardiology 1997;80:106-7.
10. Gaist, D, Jeppesen, U, Andersen, M, et al. Statins and the risk of
polyneuropathy: a case-control study. Neurology 2002;58:1333-1337.
11. Peripheral neuropathy due to statins: a rare but potentially
incapacitating adverse effect. Prescribe International 2000;9:115.
12. Crestor Package Insert. AstrZeneca Pharmaceuticals LP, Wilmington
DE:2003.
13. Olsson, AG, Pears, J, McKellar, J, et al. Effect of rosuvastatin
on low-density lipoprotein cholesterol in patients with
hypercholesterolemia. American Journal of Cardiology 2001;88:504-508.
14. Olsson, AG. A new statin: a new standard. The American Journal of
Managed Care 2001;7:S152.
15. American Medical Association Council on Ethical and Judicial
Affairs. Code of Medical Ethics, 1998-1999 Edition. American Medical
Association, Chicago, IL.
16. Braddock, CH, Edwards, KA, Hasenberg, NM, et al. Informed Decision
Making in Outpatient Practice: Time to Get Back to Basics. JAMA
1999;282:2313-20.
17. Herxheimer, A. How much drug in the tablet? Lancet 1991;337:346-8.
18. Kessler, DA, Rose, JL, Temple, RJ, Schapiro, R, Griffin, JP.
Therapeutic-class wars--drug promotion in a competitive marketplace.
New England Journal of Medicine 1994;331(20):1350-3.
19. Horton, R. The statin wars: why AstraZeneca must retreat
[editorial]. Lancet 2003 (Oct. 25);362:1341.
20. Winslow, R. Lipitor prescriptions surge in wake of big study. Wall
Street Journal, Mar. 18, 2004:D4.
21. Rosuvastatin -- a new lipid-lowering drug. The Medical Letter on
Drugs and Therapeutics, Oct. 2003;45:81-83.
22. Cohen, JS. Too Much of a Good Thing? Baycol: A Cholesterol Drug Is
Pulled after 31 People Died -- What Happened? Newsweek.MSNBC.com, Aug.
10, 2001:www.msnbc.com/news/612443.asp.
23. Temple, RJ, Himmel, MH. Safety of Newly Approved Drugs. JAMA, May
1, 2002;287:2273-2275.

Copyright 2004, Jay S. Cohen, M.D. All rights reserved. Readers have
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
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doctors.

--------------------------------------------------------------------------------

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