NEW YORK (Reuters) - A leading cardiologist on Friday disputed
Merck & Co's interpretation on the safety of patients once they stop taking
Vioxx, saying they remained at high risk
of heart attacks or strokes for some time afterward. Dr Steven Nissen, interim chairman of cardiology at the prestigious Cleveland
Clinic, said Merck misrepresented an analysis of data from a follow-up review of patients involved in the trial that led to
the pain medication being pulled from the market. "It's important that we inform people about this because
patients who have taken the drug will need increased surveillance by their physicians and increased awareness of their risks
in the year subsequent to stopping the drug. And that risk may extend beyond a year; we simply don't know," Nissen told Reuters
in a telephone interview.
Merck said on Thursday that patients who took Vioxx in the study
had no greater risk of heart attacks or strokes a year after stopping the medication than those who got placebos.
While there were 28 heart attacks or strokes in the Vioxx group compared
with 16 in the placebo group, Merck said those numbers failed to reach statistical significance.
"In the one year after Vioxx was stopped there was a 75 percent greater risk of having
an adverse event," Nissen said. {This Merck calls insignificant!} "What this
means is that, surprisingly, in the year following discontinuation of Vioxx the relative risk remains approximately as high
as it was when people were actually taking the drug. That is very clear from the data," Nissen said.
Merck withdrew Vioxx from the market in September of 2004 after a
three-year study showed it doubled the risk of heart attack and strokes in patients taking it for at least 18 months.
Nissen said because there was a relatively small total number of
adverse heart events in the follow-up year, Merck was able to claim no statistically significant difference even though the
actual numbers tell a different story. "What is important is that the hazard
stays constant even after you stop the drug," Nissen said.
In response to Nissen's comments, Merck said it stands by what it
said in Thursday's statement and subsequent conference call. "We were as transparent
as possible in this whole process," Merck spokesman Michael Heinley said. "We were trying to get out as much as we could recognizing
there were a lot of people interested in this data."
Merck is facing more than 11,500 lawsuits from people who claim to
have been harmed by Vioxx, or their survivors. The company's general counsel
said on Thursday that the one-year follow-up data should shield it from lawsuits that might be filed by people who suffered
heart attacks or strokes after they were no longer taking Vioxx.
But Nissen said: "What counts is the relative risk as you go forward,
and the bottom line is there is a constant risk even after the drug is stopped. "That
is the only clear message from the study. The rest is spin," he said
More on the killer drug:
Not safe for dogs!
Vioxx Debate Echoed in Battle Over Dog Drugs
By Marc Kaufman
Washington Post
Staff Writer
Friday, May 12, 2006; Page A01
The drug came on the market four years ago after being tested in a healthy,
young population, although it was intended for use by the old and sick. The manufacturer aggressively advertised it and ultimately
made claims deemed by regulators to be beyond what testing had established. {Marcia
Angell’s book details this and much more.}
When
reports of illness and death linked to the drug surfaced not long after it went on the market, the company was slow to report
the problems to the Food and Drug Administration. The agency eventually did issue a reprimand and a formal warning letter,
but two years later the drug is still being sold, and some consumers complain that too little is being done to warn pet owners
of its dangers. The medication is Deramaxx, and it's the center of another drug
controversy. But this medication isn't for people. It's for dogs.
An
anti-inflammatory closely related to the human painkiller Vioxx, which was taken off the market in 2004 and is now the subject
of thousands of lawsuits against Merck & Co., Deramaxx has helped relieve many canine aches and pains. But in an echo
of the national debate over the dangerous side effects of some popular human drugs, Deramaxx has also proved at times to be
deadly.
Before
the early 1990s, most drugs given to pets were human medications that appeared to help animals as well. But with dogs in particular
living longer and being treated increasingly as members of the family, the demand for better drugs has grown, along with the
public's willingness to pay for them. Most companies that now develop and sell pet drugs are subsidiaries or divisions of
the major brand-name drug companies, and they must seek FDA approval to market their products much as they do with drugs intended
for people. Deramaxx is not the only drug to run into trouble in the burgeoning
world of animal medicine. The widely used ProHeart 6 heartworm treatment was the subject of controversy several years ago
and was withdrawn from the market in 2004 following reports that healthy dogs were becoming sick and dying after getting a
shot of the preventive medicine. In both cases, the deadly side effects led to
formal -- but by many accounts ineffective -- government and industry efforts to warn veterinarians and dog owners of the
drugs' risks.
In
1999, 300 pet owners filed a lawsuit against Pfizer Inc., alleging that its early dog arthritis medicine Rimadyl had seriously
harmed their pets. Pfizer settled in 2003, saying it had done nothing wrong but wanted to avoid costly litigation. Each plaintiff
was given $1,000. The ProHeart 6 case also led to allegations that its manufacturer, Wyeth, had sought to discredit the FDA
official overseeing the investigation -- a pattern seen with FDA officials who questioned the safety of human drugs.
Victoria
Hampshire, the agency official at the center of the ProHeart 6 controversy, was taken off the case and later became a whistle-blower.
Her difficulties were documented on the Senate floor last winter by Sen. Charles E. Grassley (R-Iowa). Wyeth maintains that
it simply gave the FDA potentially troubling information it found on a Web site about a possible conflict of interest involving
Hampshire. The agency cleared her after an investigation, and ProHeart 6 remains off the market. Hampshire says she became increasingly alarmed after receiving reports of hundreds of dogs dying soon after
receiving the heartworm shots, just as more than 350 reports of deaths linked to Deramaxx have come into the FDA's Center
for Veterinary Medicine. As with adverse reactions in people, the number of reported cases is generally believed to represent
less than 10 percent of the true total.
Hampshire,
who now works in a different FDA division, said she learned about many cases from distraught pet owners such as Demitry Herman,
a manager with Lehigh Electric in Allentown, Pa.
"This
is really the same thing we saw with dangerous drugs being given to people, but maybe even more unfair because pet owners
had no idea these pills could be so harmful," said Herman, who two years ago helped start a Web site dedicated to reporting
on adverse drug reactions in dogs http://-- http://www.dogsadversereactions.com -- after his miniature schnauzer died after being given Deramaxx.
"If
our vet had only told us what danger signs to look for, maybe we could have acted sooner and she wouldn't have had to die
the miserable death she did," he said. "We know from our Web site that hundreds or thousands of dogs are dying from their
medications, and that most of their owners never even knew there was a danger."
Herman's
complaint is one that David Stansfield, director of professional relations for Novartis Animal Health, the maker of Deramaxx,
says he understands. He said the company tells veterinarians not only to inform
pet owners of possible side effects -- especially stomach problems with anti-inflammatory drugs such as Deramaxx -- but also
to conduct blood and sometimes urine tests before the drug is prescribed. Those tests can be expensive, however, and are not
routinely done.
Stephen
Sundlof, director of the Center for Veterinary Medicine, said the agency believes that pet owners need better information
about possible adverse reactions from the drugs their pets are given. But the agency cannot require veterinarians to give
out the consumer information drug companies provide, he said. "Some drugs are
not as safe as we would like them to be," Sundlof said. "We hear a lot from dog owners who lost a loved pet, and we pay a
lot of attention to that. But these drugs appear to be doing a lot of good for a lot of animals, too." Stansfield said that when it comes to treating chronic and acute canine pain, the new medicines are a major
step forward. His company has worked hard to improve its reporting of adverse events, he said, because it understands that
the benefits come with risks.
FDA's
Hampshire, who worked on the Deramaxx and ProHeart 6 cases before losing her position last year, said, "Whatever problems
we face with drugs in the human world are magnified in the animal world. There's no pharmacist involved, and so there's no
monitoring of prescriptions. And, of course, the patient can't talk and tell you he doesn't feel right." Hampshire remains concerned about her agency's response to reports of serious side effects. She likens
her experience to that of two other FDA whistle-blowers whose concerns about human drugs were not being properly addressed
-- safety officers David Graham (Vioxx) and Andrew Mosholder (antidepressants).
"Nobody
wanted to believe I was just doing my job; they wanted to think I was off on my own agenda," said Hampshire, who last month
won the U.S. Public Health Service's award for veterinarian of the year. "I think a lot of people [in the agency] didn't want
to hear what I was saying."
Because
veterinarians dispense animal drugs themselves, their role is at the center of the debate. The FDA's Sundlof and Novartis's
Stansfield said their organizations are working with veterinary groups to encourage practitioners to do more to warn clients
about possible side effects, and that many vets are responding.
But
many veterinarians resist efforts to force them to share drug information sheets -- provided by the companies and endorsed
by the FDA -- with pet owners. Elizabeth Curry-Galvin, interim director of the scientific activities division of the American
Veterinary Medical Association, said vets are trained to discuss possible drug side effects with pet owners, and her organization
thinks most do so. She said the association opposes efforts to require vets to give out the drugmakers' information because
"it's just not the be-all and end-all of the communication that's needed."
Bills
that would require distribution of the sheets have been introduced in South Carolina and Pennsylvania. The
South Carolina measure was defeated in 2004, but the Pennsylvania legislation, sponsored by state Sen. Michael J. Stack, is pending. Because of his experience with Deramaxx and later what he considers foot-dragging by the state veterinary
medicine board, Herman is pushing hard for a consumer's seat on that board. "Drugs
are needlessly injuring and killing hundreds of dogs every year," he said, "and some of us are really upset about that."
