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Does Stopping Vioxx Stop the Risk?
Experts, Drug Company Officials Disagree About Long-Term Heart and Stroke Risk
By Daniel DeNoon
WebMD Medical News
May 12, 2006 - Do strokestroke and heart attackheart attack risks linked
to the drug Vioxx continue after people stop taking it?
Yes, some leading cardiologists say. No, says Merck, which made Vioxx
until pulling the painkiller off the market in September 2004.
It's not a mere moot point. At stake is the continued safety of the many
people who took the heavily promoted drug before its risks became known.
The battle is over new data from the APPROVe study. The Merck-sponsored
study led to Vioxx's demise. It found that patients taking Vioxx during the
first three years of the study had a 92% higher risk of stroke and heart attack
than those taking an inactive placebo pill.
New "preliminary" data released yesterday by Merck show that in the year
after stopping Vioxx, the 1,721 patients still had a 74% higher stroke/heart
attack risk. During that year, 28 patients who had taken Vioxx -- and 16
patients who had taken placebo pills -- had a stroke or heart attack. Most of
these events were strokes.
This difference isn't statistically significant, meaning it could be a
chance finding. Merck says this means there isn't any risk to people who stop
taking Vioxx -- at least, no scientifically proven risk.
Not so, says cardiologist Steve Nissen, MD, interim chairman of the
department of cardiovascular medicine at The Cleveland Clinic.
"What this means is the relative risk of an event with Vioxx, even after
the drug was stopped, was very similar to the risk while taking the drug,"
Nissen tells WebMD. "It has profound implications for patients. It means that
patients who previously took Vioxx must be followed closely and must be made
aware of their increased risk."
Debate Over Meaning of Data
Michael Farkouh, MD, an expert on the heart safety of the class of drugs
to which Vioxx belongs, is director of cardiovascular clinical trials at Mount
Sinai Medical Center. He largely agrees with Nissen.
"It is concerning there is an ongoing risk from Vioxx," Farkouh tells
WebMD. "I would say the numbers are small, but they suggest an ongoing risk from
Vioxx in those who stopped taking it. There appears to be this same increase in
risk as seen while taking the drug. While the difference is not statistically
significant, it is concerning."
Merck declined WebMD's request for an interview but provided the
transcript of a telephone conference held Thursday for the financial press.
During that news conference, Merck general counsel Ken Frazier said "no
significant risk" means "no risk" in both scientific and legal terms.
"The data do not provide a valid basis or a claim that an event that
occurred after a patient stopped using the medicine was linked to the drug,"
Frazier said. "In the off-drug follow-up period for patients in this study,
there was not a statistically significant difference in the risk of confirmed
[strokestroke or heart attackheart attack] events in the Vioxx group compared to
the placebo group. So, from our perspective, we have to base our responses and
our defenses on the data as it was presented, and these data do not establish
statistically significant risk."
That statement from Merck's lawyer matches one from Merck's chief
scientist, Peter S. Kim, PhD, president of Merck Research Laboratories.
"The limited data in the APPROVe study on stroke have to be interpreted in
the context of the extensive data we have previously published, which
consistently showed no increased risk of strokes in patients taking Vioxx," Kim
says in a news release.
"Merck can't claim there isn't anything here," Farkouh says. "To claim
there is no risk is not doing patients any service. ... It does suggest there is
still ongoing risk after stopping Vioxx, although the numbers are small."
Nissen takes an even stronger stance.
"Merck misrepresented the results of the APPROVe extension in its
conference call and press release," he says. "The reason it is upsetting is that
people have a right to know what their risks are."
Permanent Damage From Vioxx?
Nissen says the new data indicate that Vioxx may cause permanent damage --
although much more information is needed to know whether this is so.
"This suggests Vioxx has more than a [blood-clot-promoting] effect," he
says. "It suggests more is going on with this drug than we thought. I would say
it is possible it causes persistent damage to the arteries."
Farkouh says the reassuring thing about Merck's new data is that the risk
of stroke and heart attack appears to be getting smaller over time. Whether that
will happen with the patients in the APPROVe trial isn't yet known. Merck is
still trying to decide whether to try to follow up with these patients.