There is a climate of elation in the world of pharma: A recent study seems to suggest that cholesterol lowering medication should perhaps be given to everyone, regardless of their level of cholesterol, to prevent future heart attacks. This is big money. At present, sales of cholesterol lowering medications are worth tens of billions of dollars, on a much more limited set of prescribing guidelines.

Yet, there are huge numbers of people suffering from the side effects of statins, which include severe muscle pains, cognitive trouble and even Amyotrophic Lateral Sclerosis and Alzheimer's disease.



Vera Hassner Sharav of the Alliance for Human Research Protection discusses the JUPITER study and its implications for our health in an article that looks at the study's limitations and inherent conflicts of interest, as well as the financial aspects of medicating healthy people to lower cholesterol.

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Pharma Marketing Tactics Threaten Public Health and Wealth
by Vera Hassner Sharav Amid much fanfare, on Sunday, November 9, AstraZeneca announced the results of its drug trial, Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER). The results were announced at the American Heart Association conference and simultaneously published in The New England Journal of Medicine (Nov. 9). The study was hailed as a watershed event in heart disease prevention: "In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels, rosuvastatin [Crestor] significantly reduced the incidence of major cardiovascular events."

Current treatment algorithms for the prevention of myocardial infarction, stroke, and death from cardiovascular causes recommend statin therapy for patients with established vascular disease, diabetes, and overt hyperlipidemia. Last year Statins commanded a $34 billion market share.

Not satisfied with selling pharmaceuticals to the sick, drug manufacturers seek to expand the market for prescription drugs to healthy people. They promote drugs as though they were toothpaste - disregarding the drugs' hazardous effects. Companies do this by persuading an unsuspecting public about the need to take drugs as a preventive measure against presumed risks of future illness. And, more importantly, drug companies set out to convince doctors - providing cash incentives - to prescribe drugs for healthy people despite documented, even life-threatening risks.

To their credit, the NEJM published an editorial by Mark A. Hlatky, M.D., who took a more critical view of the study design, its reliance on a single biomarker, CRP. He raises doubts whether the findings warrant expanded use of statins. Dr. Hlatky points to other flaws in the JUPITER study design:

"...the study provides only limited and indirect information about the role of high-sensitivity C-reactive protein testing in clinical management, since the trial did not compare subjects with and those without high-sensitivity C-reactive protein measurements, nor did it compare the use of high-sensitivity C-reactive protein with the use of other markers of cardiovascular risk."

"The relative risk reductions achieved with the use of statin therapy in JUPITER were clearly significant. However, absolute differences in risk are more clinically important than relative reductions in risk in deciding whether to recommend drug therapy, since the absolute benefits of treatment must be large enough to justify the associated risks and costs. The proportion of participants with hard cardiac events in JUPITER was reduced from 1.8% (157 of 8901 subjects) in the placebo group to 0.9% (83 of the 8901 subjects) in the rosuvastatin group; thus, 120 participants were treated for 1.9 years to prevent one event."

"On the other side of the balance, of concern are the significantly higher glycated hemoglobin levels and incidence of diabetes in the rosuvastatin group in JUPITER (3.0%, vs. 2.4% in the placebo group; P=0.01). There are also no data on the long-term safety of lowering LDL cholesterol to the level of 55 mg per deciliter (1.4 mmol per liter), as was attained with rosuvastatin in JUPITER, which is lower than in previously reported trials. Long-term safety is clearly important in considering committing low-risk subjects without clinical disease to 20 years or more of drug treatment. Finally, the cost of rosuvastatin (roughly $3.45 per day or $1,250 per year) is much higher than that of generic statins."

The cost-for the drug alone--of treating 120 people for 1.9 years to prevent one serious cardiac event would be $ 285,000.

Dr. Hlatky further notes: "Ridker et al. suggest, from their meta-regression analysis, that the risk reduction observed in JUPITER was greater than that expected on the basis of previous trials. Meta-regression is not a reliable technique, however, and the early termination of JUPITER owing to the efficacy data probably exaggerated the results to some degree."

Which brings us to the issue of conflicts of interest:

AstraZeneca funded the JUPITER study in order to justify prescribing its cholesterol-lowering statin, Crestor for people with normal cholesterol levels. Needless to say, a favorable result would exponentially increase the sales of the drug. The potential profit is in the trillions of dollars.

The research objective had a built-in bias, and the sponsor and principle investigator had a strong stake in a desired outcome. Furthermore, in light of the increased incidence of diabetes among the group prescribed Crestor (3.0%, vs. 2.4% in the placebo group), the trial's early suspension raises red flags about the extent of that (and other risks) that are known to occur mostly after extended exposure.

Not disclosed in the NEJM, is the discovery by Merrill Goozner: "the first thing you need to know about this trial is that its lead investigator, Paul Ridker of Brigham and Women's Hospital in Boston, owns a patent on the $20 test that measures CRP." (posted below)

The JUPITER trial screened nearly 90,000 people to find the 17,800 with elevated CRP measures who were eligible for the trial. If 10 million people are tested to find the estimated two million with elevated CRP levels, "it's $200 million in test sales, which, if the royalty is only 1 percent, amounts to a hefty $2 million a year in extra income for Dr. Ridker." If AstraZeneca can get two million more "apparently healthy men and women" on rosuvastatin, it's an additional $2 billion-plus in sales."

In light of AstraZeneca's record of corrupt practices[*], the following authors' statement should taken with a high degree of skepticism: "The trial was financially supported by AstraZeneca. The sponsor collected the trial data and monitored the study sites but played no role in the conduct of the analyses or drafting of the manuscript and had no access to the unblinded trial data until after the manuscript was submitted for publication."

American medicine has been derailed from its therapeutic focus and ethical principle, "first, do no harm," into a commercially driven enterprise since it aligned itself with the pharmaceutical industry. Industry's unconscionable marketing strategy - promoting the use of drugs for healthy people - is accomplished with assistance from professional medical societies and influential physicians at prestigious academic centers.

Doctors have adopted a specious corporate rationale to justify prescribing drugs for healthy people as "preventive therapy." All-too-often, doctors accept findings from company-controlled, biased studies, ignoring the indicators for potential serious hazards posed by drugs. In the case of the JUPITER study, there was "a higher incidence of physician-reported diabetes" in the group exposed to Crestor.

Doctors at the American Heart Association, lent legitimacy to prescribing statins for long-term use in healthy people, simply on the basis of a screening test that showed they had elevated levels of CRP, a biomarker for inflammation. They predicted that the JUPITER study might lead as many as 7 million more Americans to consider taking cholesterol-lowering statin drugs, such as: Crestor, Lipitor, Zocor,

Similarly, the prescribing practices of US psychiatrists are driven by industry's marketing agenda with no scientific medical evidence to support the widespread prescribing of psychotropic drugs. Dubious screening tests - such as DISC, TeenScreen, KiddieSADS, TRAYY - provide the basis for "diagnosing" mental disorders in millions of otherwise healthy American children who are then exposed to harmful toxic drugs that interfere with normal physiological and neurological development. Even as these drugs' labels now carry black box warnings, the most severe drug warnings mandated by the FDA-including the increased risk of suicide-prominent psychiatrists promote the use of these drugs in children. Financially compromised psychiatrists regularly pen their name (for hefty fees) to industry-generated clinical trial reports and clinical practice guidelines whose prescription drug recommendations have propelled the most toxic psychotropic drugs into blockbuster sellers.

*AstraZeneca in the news:

Nov. 6, 2008: Astra Zeneca Reps Told To Use Disney Characters In Seroquel Marketing
How is this for creative selling? The idea was conveyed at a national sales meeting and on field rides with sales reps, who were told to use Tigger as a bipolar patient and Eeyore - the down-in-the-mouth donkey - as a depressed patient. The reps were allegedly encouraged to use Tigger dolls as giveaways." See: http://www.pharmalot.com/2008/11/tiggergate-using-disney-icons-to-sell-seroquel/

June 19, 2008: Judge Price of the Montgomery County Circuit Court upheld the fraud verdict obtained by the State against AstraZeneca in the Medicaid drug pricing suit
Judge Price upheld the compensatory damage award of $40 million and, pursuant to the statutory cap on punitive damages, cut the punitive damages from $175 million to $120 million, making the total verdict $160 million. AstraZeneca has stated they will appeal, so the Alabama Supreme Court will be looking at it. For more information, follow the link to an article on Forbes: http://www.forbes.com/feeds/ap/2008/06/19/ap5134622.html

May 6, 2008: AstraZeneca released limited performance data for a trial using its antipsychotic, Seroquel for depression
The company released the data during a poster session at the American Psychiatric Association's convention. The data has not been published yet in a peer-reviewed journal, so we have no information on drop out rates or whatever statistical methodology may have been used. The expanded use of antipsychotics for depression would represent a "huge tectonic shift" in treating depression - and a huge influx of profits. AZ hadn't released any efficacy data for Seroquel XR's performance versus placebo in treating depression (or Major Depressive Disorder, as AZ has it). See Furious Seasons article: Astra Zeneca releases limited Seroquel data for depression

April 6, 2007: AstraZeneca, 'Bucket of Money'
Group of 7 Whistleblowers Allege Off-Label Campaign for cancer drug, Faslodex, "There is a big bucket of money sitting in every office. Every time you go in, you reach your hand in the bucket and grab a handful. The more times you are in, the more money goes in your pocket. Every time you make a call, you are looking to make more money." See: http://www.brandweeknrx.com/2007/04/az_bucket_of_mo_1.html and http://tinyurl.com/5sjuq7

June 21, 2003: AstraZeneca, the large pharmaceutical company, pleaded guilty today to a felony charge of health care fraud and agreed to pay $355 million to settle criminal and civil accusations that it engaged in a nationwide scheme to illegally market a prostate cancer drug. The government said the company's employees had given illegal financial inducements to as many as 400 doctors across the country to persuade them to prescribe the drug, Zoladex. Those inducements included thousands of free samples of Zoladex, worth hundreds of dollars each, which the physicians then billed to Medicare and other federal health care programs, prosecutors said. The company also gave doctors financial grants, paid them as consultants and provided free travel and entertainment, the government said. See: AstraZeneca Pleads Guilty In Cancer Medicine Scheme By MELODY PETERSEN, The New York Times

Contact: Vera Hassner Sharav
veracare@ahrp.org
212-595-8974

http://www.gooznews.com
November 09, 2008

CRP -- The Next Chapter in Medical Waste?

The latest study on statins and heart disease, which appeared in the New England Journal of Medicine website yesterday and in all the major papers this morning, is worth a second look, not because of what it says about heart disease, which is mildly interesting at best, but because of what it reveals about profit-driven medical research and how it contributes to making the U.S. health care system the most bloated and wasteful in the world.

Whole article at http://www.gooznews.com/archives/001243.html