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November 8, 2004

BehindTheMedspeak: 'I have never read a more powerful editorial in a medical journal'

Vioxx1

Dr. Eric Topol, speaking about last week's blistering Lancet editorial about Vioxx.

The editorial accompanied a Lancet article which concluded that Vioxx should have been withdrawn from the market as early as 2000 because studies of the drug had clearly shown that it doubled the risk of heart attacks among users.

Richard Horton, editor of The Lancet, wrote, "with Vioxx, Merck and the F.D.A. acted out of ruthless, short-sighted and irresponsible self-interest."

He described Vioxx's approval and subsequent popularity until its recent recall as "public health catastrophes" that led to over 27,000 heart attacks and sudden deaths.

That's a lot of corpses on Merck's corporate conscience.

Merck replied that it "was vigilant in monitoring and disclosing the cardiovascular safety of Vioxx, and we absolutely disagree with any implication to the contrary."

Dr. Sandra Kweder, the deputy director of the F.D.A.'s Office of New Drugs, said that many of Horton's assertions were "flat-out wrong."

Topol, a cardiologist at the Cleveland Clinic who was one of the first to call attention to the heart problems presented by Vioxx, said, "it is unquestionable that the risks of the drug were known some time ago and not duly acknowledged, and this study is the best yet to prove that."

bookfofjoe aside: Pfizer, the other maker of cox-2 inhibitors (Celebrex and Bextra), is claiming its drugs are different from Vioxx, and therefore safe.

Pfizer's even proposing to begin a study showing Celebrex protects against cardiovascular problems.

Don't believe it.

Read this article about the likelihood that all these drugs work the same way and are likely to have the same side effect profile.

I say to you: throw these drugs in the trash and use something else.

They all have the same mechanism of action

20040204_210249_vioxxaction

and work via the same pathway.

Here's last Friday's New York Times story by Gardiner Harris about the growing controversy.
____________________


Study Says Drug's Dangers Were Apparent Years Ago


Merck and federal officials should have withdrawn the painkiller Vioxx from the market as early as 2000 because studies of the drug had clearly shown that it doubled the risk of heart attacks among users, according to a study released yesterday by The Lancet, a British medical journal.

Authors of the study pooled data from 25,273 patients who participated in 18 clinical trials conducted before 2001.

They found that patients given Vioxx had 2.3 times the risk of heart attacks as those given placebos or other pain medications.

Merck withdrew Vioxx on September 30 of this year after a company-sponsored trial found a doubling of the risks for heart attack or stroke among those who took the medicine for 18 months or more.

An editorial accompanying the study criticized both Merck and the Food and Drug Administration, and described Vioxx's approval and its popularity as "public health catastrophes" that led to over 27,000 heart attacks and sudden deaths.

"For with Vioxx, Merck and the F.D.A. acted out of ruthless, short-sighted and irresponsible self-interest," wrote Richard Horton, editor of The Lancet.

In a statement, Merck said that the Lancet study was not comprehensive or new. "Merck was vigilant in monitoring and disclosing the cardiovascular safety of Vioxx, and we absolutely disagree with any implication to the contrary," the company said.

The Lancet study increases pressure on the F.D.A., which is dealing with allegations that it tried to squelch prescient warnings by its own drug-safety reviewers about the dangers of Vioxx and about the hazards of antidepressant use by children and teenagers.

Committees in the House and Senate are investigating the F.D.A.'s handling of those issues. More hearings are expected.

In his editorial, Mr. Horton wrote that the F.D.A. failed to act after a 2001 analysis demonstrated the risks of Vioxx. He called for a thorough revamping of the agency's process for reviewing drug safety.

Dr. Sandra Kweder, the deputy director of the F.D.A.'s Office of New Drugs, said that many of Mr. Horton's assertions were "flat-out wrong."

She noted that the entire heart attack risk found when pooling data of the 18 Vioxx studies came from a single study.

The F.D.A. examined the results of that trial closely, Dr. Kweder said, and the agency made sure Merck was conducting more studies on the matter.

"We knew we were getting more data as well as ongoing studies and ongoing placebo-controlled studies that could be extremely useful in answering the question" of whether Vioxx caused heart attacks, she said.

Dr. Eric Topol, a cardiologist at the Cleveland Clinic and one of the first to call attention to the heart problems presented by Vioxx, said in an interview that he had never read a more powerful editorial in a medical journal.

"It is unquestionable that the risks of the drug were known some time ago and not duly acknowledged, and this study is the best yet to prove that," Dr. Topol said.

Tony Butler, an analyst for Lehman Brothers, said that the recent slide in Merck's share price - down 40% since September 29 - suggested that investors believe that Merck's liability for Vioxx is about $20 billion.

Mr. Butler said that projection is highly inflated, because very few drug withdrawals result in such a huge legal bill.

"The fears expressed by so many others seem exaggerated with the information that we know today," Mr. Butler said.

Vioxx is a member of a class of painkillers called cox-2 inhibitors, which also includes the Celebrex and Bextra drugs made by Pfizer.

Studies in patients undergoing cardiac surgery have found that Bextra increased risks to the heart.

In rare cases, Bextra can also cause a fatal skin reaction.

Pfizer has said that Celebrex had not been found to pose cardiac risks.

But Pfizer shares tumbled Thursday after The National Post in Toronto reported that Celebrex may have contributed to at least 14 deaths, according to incidents reported to Canada's health regulator.

Pfizer called the article "misleading" and Maria Valois, a top official at Health Canada, noted that the data cited by the newspaper was difficult to interpret.

"The crude number of events cannot be used to estimate the risk" of Celebrex or any other drug, Dr. Valois said in a telephone conference with reporters.

Health Canada has asked Pfizer for more safety data, Dr. Valois said.

Earlier in the day, Pfizer shares fell to $27.20, a 52-week low.

But by the end of trading on the New York Stock Exchange yesterday, Pfizer's stock had largely recovered, closing at $29.06, down 39 cents.

Top F.D.A. officials have said that the agency had no data indicating that Celebrex or Bextra resulted in elevated risks to the heart.

Vioxx

Early next year the agency will convene a panel of outside experts to review the evidence regarding the entire cox-2 class of medicines.

November 8, 2004 at 01:01 PM | Permalink


Comments

I have been watching the all negative articles in the wall street journal in the past year. They also usually run positive articles or comparisons to Pfizer. I was then told that Pfizer's chairman is on the board of WSJ's parent. I wonder how objective a business publication that has a huge impact on a stock's performance can be with various company heads on the board.
I agree that patients need to be told everything that is known about a drug. I don't believe Merck hid information. What can be done to prevent a Vioxx situation again? I don't know. More testing? People are already complaining about the high drug prices so let's add more cost?

Posted by: brent | Nov 9, 2004 11:26:42 AM

Part of the reason the Lancet's editorial was so blistering is that the FDA posted a paper to its website that the Lancet was considering for publication. Journals don't like that one little bit.

See my post on this topic at: http://www.journalclub.org/2004/11/08/n16

Posted by: Michael Jacobson | Nov 8, 2004 10:30:35 PM

Speaking as someone who has had severe and sometimes debilitating arthritis for the last few years (I'm only 32), what drug doesn't have a risk?

I've never tried Vioxx but I have been on several other nasty ones that are toxic to the liver and other organs and are potentially fatal if ignored... methotrexate is one of these and is pretty nasty, but I'd rather have use of my knees and wrist knowing full well that I might be taking years off my life in doing so.

Life is not worth living if you can't actually live it...

Joe - sometimes I read your medical articles and it seems that you think the public are sheep.

It seems this site is geared toward at least a college-level audience, so I'd assume most, if not all, understand the statistics that are presented in almost every new prescription.

Yeah, the nasty parts are hidden behind cold formulas and all, but it's not really that difficult to read.

Anyone who cares at all what the drug is doing will have looked at this and seen the results....

Or they will simply be happy they can get on their feet in the morning and walk around without anyone knowing they have to take a cocktail of meds each night just to allow this miracle to occur, while knowing the potential side effects are well worth the risk.

Posted by: Arthritis Sufferer | Nov 8, 2004 3:59:42 PM

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