Healthy Skepticism Library item: 4515

Warning: This library includes all items relevant to health product marketing that we are aware of regardless of quality. Often we do not agree with all or part of the contents.

Publication type: news

Armstrong D.
Critical Dose Aspirin Dispute Is Fueled by Funds Of Industry Rivals
The Wall Street Journal 2006 Apr 24
http://online.wsj.com/article/SB114583660487933679.html

Keywords:
aspirin Plavix

Notes:

Ralph Faggotter’s Comments:

“ Physician’s Weekly Managing Editor
Keith D’Oria says he knew of the ties, but didn’t disclose them. He said
the publication never discloses possible conflicts and instead uses the
information for other purposes, such as contacting drug companies listed
by doctors to see if they might place an ad near the doctor’s commentary. “

This form of value adding through a process of mass deception of the readership is common throughout the Media, but it is rare to see this blatantly unethical activity admitted to by such a frank disclosure.

What does this tell us about the editor’s opinion of his readership?

“There is a real issue of who you can get unbiased opinion from in
medicine,…”

This is the crux of much of the uncertainty and loss of confidence in Medicine today- and the problem will not go away until the ‘experts’ are weaned from industry funding and can therefore be seen to be more objective in their assessments.

Full text:

Critical Dose Aspirin Dispute Is Fueled by Funds Of Industry Rivals

http://online.wsj.com/article/SB114583660487933679.html

By DAVID ARMSTRONG, Wall Street Journal, April 24, 2006; Page A1
(copied as fair use)

Over the past four years, medical publications have become full of talk
about “aspirin resistance” — suggesting that millions who take an
aspirin a day to prevent heart attacks are wasting their effort. If that
is true, widespread testing might be needed to detect the condition and
doctors might have to turn to aspirin substitutes costing $4 a day.

But reports and commentary on the subject often fail to point out that
many of those raising alarms about aspirin resistance have financial
ties with drug and test makers who stand to profit from the idea’s
acceptance.

Last July, Harvard Medical School associate professor Daniel Simon
warned that aspirin resistance may afflict as many as 30% of the 25
million Americans taking aspirin for their hearts. He wrote in
Physician’s Weekly, a trade publication, that these people are at higher
risk for heart attacks and strokes and may need other anticlotting drugs.

The article didn’t mention that Dr. Simon receives research funding from
Accumetrics Inc., a privately held San Diego company that makes a test
to measure aspirin resistance, and from pharmaceuticals maker
Schering-Plough Corp., which sells a drug being tested as a potential
benefit for patients deemed aspirin-resistant. He is also a consultant
and paid speaker for Schering-Plough. Physician’s Weekly Managing Editor
Keith D’Oria says he knew of the ties, but didn’t disclose them. He said
the publication never discloses possible conflicts and instead uses the
information for other purposes, such as contacting drug companies listed
by doctors to see if they might place an ad near the doctor’s commentary.

The issue of aspirin resistance is a powerful example of how key
academic researchers with a financial interest can influence the care
Americans receive. Fears of aspirin resistance have boosted sales of the
anticlotting pill Plavix, the world’s second best-selling drug after
cholesterol fighter Lipitor. Even some doctors who are trying to debunk
aspirin resistance have financial ties — to aspirin maker Bayer AG.

“There is a real issue of who you can get unbiased opinion from in
medicine,” says John Eikelboom, a hematologist at McMaster University in
Hamilton, Ontario, who has consulted for both an aspirin manufacturer
and the maker of an alternative blood-thinner. “It is a terrible
problem…I try to be honest with myself, but I can’t pretend I will
always be as honest as necessary.”

Mark Feldman, chairman of internal medicine at Presbyterian Hospital of
Dallas, says much of the talk about aspirin resistance is generated by
“companies pushing these tests.” He recommends against testing and
worries that some doctors are upping the dosage of aspirin for patients
deemed resistant, which he says increases the risk of gastrointestinal
problems for those patients.

Harvard’s Dr. Simon, who will take up a new position in July as chief of
cardiology at Case Western Reserve University in Cleveland, says it’s a
mistake to tune out the views of those with some conflicts of interest
because industry is driving medical advances. Most unconflicted
researchers “are not truly expert,” he says.

Aspirin, which costs pennies a pill, inhibits sticky fragments in the
blood called platelets. They pool together to form clots that can block
arteries, causing heart attacks and strokes. The American Heart
Association recommends that those who have suffered a heart attack or
stroke take one aspirin a day, based on studies showing this regimen can
reduce heart attacks and strokes by around 25%. Many doctors also
prescribe aspirin for others at risk, such as overweight men over 40,
and recommend a baby dose (81 milligrams) to limit potential damage to
the stomach.

Aspirin resistance was little studied until 2002, when more than a dozen
research reports on it were published. Each successive year has seen an
increase in research work and publications on the topic.

Today, it’s widely agreed that aspirin fails to have an anticlotting
effect in at least a small number of patients. But critical questions
remain unresolved, including how many such patients there are and how
high their cardiovascular risk is. Perhaps most importantly, research
has yet to show whether any drug or treatment can help aspirin-resistant
people.

A 2002 study by Dr. Eikelboom and colleagues found that a high level of
aspirin resistance — as measured by a certain urine test — could more
than triple the risk of cardiovascular death. However, Dr. Eikelboom now
says the urine test is “the wrong marker” and shouldn’t be used to test
for aspirin resistance.

Amid the uncertainty, doctors are increasingly testing patients for
resistance and prescribing aspirin alternatives. Medicare, the federal
health insurer for the elderly, says it paid for 43,000 laboratory tests
used to measure aspirin resistance in 2004, which was double the number
of tests it paid for just two years earlier. Dade Behring Inc. of
Deerfield, Ill., reported last year that sales of its machine for
measuring aspirin resistance “continued to grow in double digits.”

Cardiologist Roger Acheatel of Escondido, Calif., began testing all of
his patients who take aspirin for resistance after reading about the
topic in the medical literature. He uses the Accumetrics test, which is
covered by Medicare and most insurers. The test costs doctors and
hospitals about $20 to $22. Medicare reimburses $30 for the test.

Dr. Acheatel often prescribes Plavix, which is sold by Bristol-Myers
Squibb Co. and Sanofi-Aventis SA, for patients found to be
aspirin-resistant. “Why deny people treatment?” he asks, adding that
patients who are not tested for aspirin resistance are “behind the curve.”

World-wide sales of Plavix reached $5.9 billion last year, according to
IMS Health Inc., up 59% from two years earlier. Plavix, also known by
the generic name clopidogrel, stops clotting via a mechanism that is
different from aspirin’s. Doctors often prescribe both aspirin and
Plavix for patients receiving cardiac stents, which increase clotting
risk. Online pharmacies quote a price of $4 to $4.50 for a daily dose of
Plavix.

“Before Plavix we rarely heard a mention of aspirin resistance,” says
Sanjay Kaul, director of cardiology training at Cedars-Sinai Medical
Center in Los Angeles. “One has to wonder if the commercial implications
of this phenomenon trump scientific reality.” Dr. Kaul says he doesn’t
test patients for aspirin resistance and accepts no industry funding or
consulting work.

A Bristol-Myers spokesman denied that the company is seeking to
undermine aspirin, saying there would be “no advantage” to doing so
because Plavix is often taken together with aspirin.

Adding Plavix to aspirin as a preventative measure, however, appears to
do little good and may also be harmful in some cases, according to a
recent study. Published in the New England Journal of Medicine, the
study said Plavix plus aspirin wasn’t any more effective than aspirin
alone in preventing heart attacks, strokes or deaths from cardiovascular
disease. In one group of patients — those who hadn’t already had a
heart attack or stroke — the addition of Plavix increased the risk of
death and bleeding complications. The study of more than 15,000 patients
was funded by Plavix’s makers.

The study does not mean Plavix is not effective in other situations.
Days after the study results were announced, the country’s two top
cardiology organizations advised heart patients not to stop their Plavix
treatment, especially if they had a drug-eluting stent implanted. Plavix
is approved for patients with a recent heart attack or unstable chest
pain, and for people treated with drug-eluting stents.

Among those lending credence to aspirin resistance has been Eric Topol,
who recently left his position as head of cardiology at the Cleveland
Clinic after clashing with Chief Executive Delos “Toby” Cosgrove. Dr.
Topol is one of the world’s most-cited authorities on the heart.

Dr. Topol co-authored an influential 2003 Cleveland Clinic study
published in the Journal of the American College of Cardiology. It
reported that among those taking aspirin, resistant people were three
times as likely to die or suffer a heart attack or stroke as those who
responded normally to aspirin.

The authors speculated that “future treatment of aspirin resistance with
additional antiplatelet agents such as clopidogrel [Plavix] may
significantly improve the poor prognosis.” Several hospitals have cited
the Cleveland Clinic study as backing for their decision to adopt the
Accumetrics test.

The study looked at 326 patients, 17 of whom were determined to be
aspirin resistant. Of those 17, four suffered either a death, a heart
attack or a stroke. If just one fewer patient had died or suffered a
stroke or heart attack, the result would have lacked statistical
significance, according to Steven Steinhubl, a University of Kentucky
cardiologist who conducts aspirin-resistance research and consults for
several companies making anticlotting drugs.

The Cleveland team also used another method for determining aspirin
resistance. Under that method, there was no statistically significant
difference between the aspirin-resistant group and the normal group. But
that result wasn’t published. Dr. Steinhubl says the decision to publish
only one result skewed the conclusion to a more alarmist one. “If you
see what you want to see, you publish it,” he says.

Dr. Topol says the test used in the published study is the “gold
standard.” He notes that even with the other test there was an
indication of risk from aspirin resistance although the data weren’t
statistically significant.

In June 2004, Dr. Topol was quoted in an Accumetrics press release as
saying that its aspirin test was “prototypic of the future of
individualized medicine” and would allow doctors to “improve outcomes
for a large number of patients.” Dr. Topol says he never authorized the
quote in the press release and it is inaccurate. Robert Hillman, chief
executive of Accumetrics, said in an email that “it’s impossible for me
to recall the exact circumstances” of the release.

Although the press release didn’t mention it, Dr. Topol at the time was
a consultant to Accumetrics and also advised another aspirin
resistance-testing firm, AspirinWorks, a division of Creative Clinical
Concepts Inc. of Denver. He also served as a consultant to companies
making or developing aspirin alternatives, including Bristol-Myers,
Sanofi-Aventis, Eli Lilly & Co., and Medicines Co. All were paid
positions, Dr. Topol says.

Dr. Topol says he has always been careful to avoid recommending that
patients be tested for aspirin resistance. He says he has called for
more thorough studies of the subject. In the case of Accumetrics and
AspirinWorks, Dr. Topol says he was given shares in the companies in
exchange for his consulting work. He says he forfeited those stakes in
2004 as part of a broader decision to sever financial ties with industry
to avoid the perception of conflicts. “I never profited in any way from
my work with Accumetrics or the company that developed the AspirinWorks
assay,” he says.

In addition to consulting with Accumetrics, Dr. Topol helped the company
get venture-capital funding. In April 2003, Essex Woodlands Health
Ventures of Chicago listed Dr. Topol as an “adjunct partner” who
provided advice on “all aspects of the venture capital process.” Essex
Woodlands led a $13.5 million round of investment in Accumetrics in
March 2004 and has since invested more in the company.

Dr. Topol “was certainly one of the individuals who played a factor in
connecting us” with Accumetrics, says Immanuel Thangaraj, a managing
director of Essex Woodlands. Mr. Thangaraj declined to say how much his
firm paid Dr. Topol for the part-time position. Dr. Topol says he
doesn’t remember what he was paid.

Besides their research work, Dr. Topol and his Cleveland Clinic
colleagues hit the lecture circuit to build awareness of aspirin
resistance. At the annual meeting of the American Heart Association in
November 2004, a packed room of doctors attended a symposium co-led by
Dr. Topol: “The Cleveland Clinic Presents the Diagnosis and Management
of Antiplatelet Resistance.” Accumetrics and two drug companies making
anticlotting drugs were among the event sponsors.

Dr. Eikelboom of McMaster University said he disagreed with the tenor of
the symposium. “I was upset because I don’t think we ought to be
promoting testing for aspirin,” he says, citing the lack of evidence
that changing treatment for aspirin-resistant patients does any good.
Dr. Topol’s own comments at the symposium didn’t promote testing,
according to a transcript.

Harvard’s Dr. Simon is about to enroll the first patient in a more than
$2 million, 600-patient study that will use the Accumetrics test to
determine if patients about to undergo angioplasty — or unblocking of
arteries — are resistant to aspirin or Plavix. (Accumetrics now also
makes a test to measure Plavix resistance.)

Patients classified as resistant will be placed into two groups — one
receiving Integrilin, an injectable anticlotting medication sold by
Schering-Plough, and one receiving a placebo. The researchers will
compare the two groups for differences in heart-attack rates. The study,
initiated by Dr. Simon, is funded by Accumetrics and Schering-Plough.

Cardiologist Sidney Smith, a former American Heart Association
president, says the federal government should fund an independent study
to answer questions about aspirin resistance.

Some of the strongest criticisms of aspirin resistance have come from
researchers with ties to Bayer. In December, the New England Journal of
Medicine published a review article that concluded that none of the
aspirin tests “is currently recommended” and that there was “no
scientific basis for changing antiplatelet therapy.” The four authors of
the article all had financial ties to Bayer, which were disclosed.

In September 2004, the journal Circulation published a “special report”
on aspirin resistance that warned the “current usage of the term aspirin
resistance implies a linkage between a laboratory test and a clinical
outcome that is presently unsubstantiated.”

The lead author of that report, epidemiologist Charles Hennekens of the
University of Miami School of Medicine, reported that he was a
consultant for Bayer. The report didn’t have disclosures regarding two
other authors with Bayer connections: Steven Weisman, a former Bayer
executive who remains a consultant to the company, and University of
Pennsylvania researcher Garret FitzGerald, a Bayer consultant at the
time the article was published.

A spokeswoman for the American Heart Association, which publishes
Circulation, said the other authors reported their connections to Bayer
but the information was omitted because of a production error. Dr.
FitzGerald confirmed that he disclosed the relationship at the time the
article was submitted.

Dr. Hennekens, who conducted a landmark study in the 1980s demonstrating
the benefits of taking an aspirin a day, has been particularly critical
of aspirin resistance. In a December 2004 commentary in Physician’s
Weekly, Dr. Hennekens cautioned that “exaggerated concern about this
undocumented phenomenon may have the negative consequence of reduced
aspirin use.” His connection to Bayer was not disclosed in that article.
He did not respond to telephone and email messages seeking comment.

Write to David Armstrong at david.armstrong@wsj.com1 URL for this article:
http://online.wsj.com/article/SB114583660487933679.html
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