Jay S. Cohen M.D.   http://medicationsense.com 1337 Camino Del Mar   Suite C   Del Mar, CA 92014   Phone: 858.345.1760   Fax: 858.509.8944


Pushing High-Dose Lipitor: Medical Science or Slick Marketing?Marketining?

Thousands of Drug Sales Reps Are Influencing Doctors to Prescribe High-Dose Lipitor despite Ongoing Concerns about Efficacy and Safety.  Does the Pharmaceutical Industry Place Sales over Safety?

In 2005 and 2006, large studies were published on the use of maximum-dose 80-mg Lipitor, the top-selling cholesterol-lowering statin drug, to prevent heart attacks and strokes.1,2  The 2005 study showed a reduction in deaths from heart attacks with high-dose Lipitor (atorvastatin).  This was a positive result, but not positive was the finding that more people taking high-dose Lipitor died from other causes.  In the 2006 study, high-dose Lipitor was barely better than placebo in preventing recurrent strokes, and just as many people died with high-dose Lipitor as with placebo.  In both studies, liver injuries occurred nearly 5 to 7 times more often in high-dose Lipitor patients.  Taken together, these findings raise serious questions about the efficacy and safety of high-dose Lipitor.

If doctors read these studies carefully, it should cause them to use high-dose Lipitor sparingly, except perhaps for people who have advanced cardiovascular disease or who do not respond to lower doses.  In contrast, the studies, which were funded by Lipitor's manufacturer, Pfizer, called for the widespread use of high-dose Lipitor for all people at risk for heart attacks or strokes.  This would mean millions of people.

The Marketing of High-Dose Lipitor
The indiscriminate use of the most powerful dose of a very powerful statin drug may benefit people who really need intensive treatment.  However, it will also cause the overmedication of many others, perhaps numbering in the millions.  People will be beset with side effects, which can be very serious.  Muscle weakness, joint pains, and memory problems can impair normal functioning.  Muscle degeneration from statins has caused kidney failure and death.  Liver injuries have progressed to liver failure and death.  These side effects are all dose-related: the higher the dose, the greater the risk.  This is why I am against the indiscriminate use of high-dose Lipitor: it places too many people at extra risk.

Side effects will also force many people to discontinue treatment.  Others will be burdened by the high cost of Lipitor, an expensive, brand-name drug.  But these are patients' problems, not Pfizer's, which profits every time a prescription for high-dose Lipitor is filled.

When Pfizer or any drug company undertakes large, expensive studies, it should be understood that the company has an agenda.  Drug companies have learned that publishing major studies in medical journals can attract a great deal of media attention.  Both studies of high-dose Lipitor received major coverage from the media.  Pfizer dispatched thousands of sales reps to doctors' offices to tout high-dose Lipitor.  The campaign to push doctors to prescribe more high-dose Lipitor was on.

If you think I am exaggerating, consider this.  According to an August 2006 report in Bloomberg News,

    "Pfizer said Wednesday that it had increased second-quarter revenue from its Lipitor cholesterol pill by persuading doctors to prescribe more expensive doses of the drug, the best-selling prescription medicine....  Pfizer, the world's biggest drug maker, said it sent thousands of sales people to doctors' offices to tout studies showing that higher doses cut the risks of heart attack, stroke and death better than do other cholesterol drugs.3"

I would guess that the sales reps did not mention the increased incidence of liver injuries or the failure to reduce overall deaths with high-dose Lipitor.

Maximizing Profits Instead of Safety
Why is Pfizer pushing high-dose Lipitor so hard now?  The answers lie in the marketplace.  First, a 80-mg pill of Lipitor costs about $3.33, about 36 percent more than the 10 mg pill, which costs only $2.44.  That's an extra $27 dollars in sales for every 1-month prescription of 80-mg Lipitor -- or $325 dollars per year per patient – in comparison to 10-mg Lipitor.  Multiply this by about 5 million people, and an additional $1.6 billion dollars in sales are generated each year.

Another reason for the high-dose Lipitor onslaught is that Pfizer is responding to new challenges in the marketplace.  Zocor (simvastatin), a major competitor of Lipitor for a decade, is now available as a generic drug.  Other popular statins such as Mevacor (lovastatin) and Pravachol (pravastatin) are also available as lower priced generics.  This has placed Lipitor, which generated 40% of Pfizer's profits in 2005, at a huge cost disadvantage.3  In response, Pfizer is using the studies of high-dose Lipitor to convince doctors and patients to rely only on brand-name Lipitor.  If this was Pfizer's plan, it is working.

You have to give Pfizer credit for its marketing prowess, but there are medical concerns and ethical problems with pushing high-dose Lipitor this way.  Why should patients have to shoulder the cost and run the extra risks of high-dose Lipitor when lower doses of Lipitor and other statins are often effective and safer?  Pfizer's actions may also be short sighted.  Many drugs have been withdrawn or fallen into disfavor because of overly aggressive dosing that provoked serious side effects.  It doesn't take many reports of serious injury or death to give a good drug a bad name.  Lipitor is a useful drug, but any drug will cause harm if the doses are too strong and patients are overmedicated.

Should You Use High-Dose Lipitor?
If you have cardiovascular disease or are at high risk for it, higher doses of a statin drug may be warranted.  However, high-dose statins such as Lipitor are not usually warranted for people who are healthy and who merely have elevated cholesterol.

Even if you have coronary artery disease and warrant high-dose statin therapy, you may find that 80-mg Lipitor is too strong for you.  Studies have shown that some people are sensitive to the effects of statin drugs, and these people often obtain good responses with lower doses.  The drug companies claim that statin side effects are infrequent, but practicing physicians say otherwise.  Side effects are one of the reasons that the great majority of people prescribed statins ultimately discontinue treatment.  It is better to start with a lower, safer dose of statin medication and stay in treatment than to get overmedicated, develop side effects, and quit.

If you require vigorous lowering of your LDL cholesterol, consider using a combination approach: a heart-healthy diet, a low or moderate dose statin, and other drugs that block cholesterol absorption from the gut or lower cholesterol by other mechanisms.  Indeed, a good diet by itself can lower cholesterol as much as a moderate-dose statin drug.

Low-dose statins can also be quite effective for lowering LDL cholesterol. In the 2005 high-dose Lipitor study, low-dose 10-mg Lipitor was also studied.  Low-dose Lipitor lowered the average LDL level to 101 mg/d, and side effects and patients discontinuing treatment were fewer.  This was a very good result, and many patients attained even lower LDL levels.  Although Pfizer is trying to convince us that only high-dose Lipitor will do, lower doses of Lipitor (2.5, 5, 10, 20, 40 mg) and other statins are not only effective for many people, but also safer and less expensive.

Interestingly, in an expert editorial that accompanied the 2005 high-dose Lipitor study, Dr. Bertram Pitt expressed concerns about the safety of high-dose Lipitor.  He noted that high-dose Lipitor showed no benefit on overall mortality, and he described this finding as "a matter of concern."  Dr. Pitt advised against using high-dose Lipitor: "We need further reassurance as to the safety of this approach...."  Instead, Dr. Pitt recommended a combination approach (as I have described above) to reducing LDL cholesterol to low levels.4

Do you think that when the Pfizer drug reps give promotional materials on high-dose Lipitor to doctors, they include Dr. Pitt's editorial?  Not likely.  The goal is sales, not safety.  The drug companies learned long ago that slick marketing can convince doctors to prescribe almost anything.  This has been proven again and again with Propulsid, Redux, Rezulin, Vioxx, and Bextra, to name a few of the drugs made bestsellers by doctors--until yanked because of toxicity.

High-dose Lipitor is a powerful drug.  When used cautiously, it can do a lot of good.  If used indiscriminately, it can do considerable harm.  If your doctor recommends high-dose Lipitor, ask why.  Read the studies.  Inform yourself and make up your own mind.  If you have doubts, ask about starting with a low dose of Lipitor or with another, less expensive statin.

February 2007

References
1.  LaRosa JC, Grundy SM, Waters DD, et al.  Intensive lipid lowering with atorvastatin in patients with stable coronary disease.  New England Journal of Medicine 2005;352:1425-35.
2.  Stroke prevention by aggressive reduction in cholesterol levels investigators.  High-dose atorvastatin after stroke or transient ischemic hepatic.  New England Journal of Medicine 2006;355:549-559.
3.  Pettypiece S.  Pfizer lifts Lipitor profit by promoting  larger, pricier dose.  Bloomberg News, Thurs., Aug. 24, 2006:  www.bloomberg.com/apps/news?pid=20601086&sid=aU0FKY3RaHIM&refer=news.  Accessed 8/25/06.
4.  Pitt B.  Low-density lipoprotein cholesterol in patients with stable coronary heart disease -- is it time to shift our goals?  New England Journal of Medicine 2005;352(14):1483-1484.





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