Vioxx,
Merck’s blockbuster arthritis drug, was recalled from
the market last September after questions were raised about
the cardiovascular risks associated with the drug. In a press
release after the recall, Merck’s CEO Raymond Gilmartin
claimed that his company was “putting patient safety
first” and called the heart attack risk that led to
the recall “unexpected.” Internal company documents,
however, suggest that Merck was aware of the cardiovascular
risks associated with Vioxx years ago, even before the drug
was approved for the general public.
Vioxx was one of a new class of painkillers called COX-2
inhibitors. These drugs reduce the pain and inflammation associated
with arthritis without the side effects (primarily stomach
upset) associated with older non-steroidal anti-inflammatory
drugs like aspirin and Aleve (naproxen). NSAIDs worked by
blocking both of the enzymes involved in causing inflammation,
COX-1 and COX-2.
Unlike those drugs, Vioxx inhibits only production of COX-2
and therefore is easier on the stomach, since blocking the
COX-1 enzyme can lead to stomach irritation in some patients.
Thus, the advantage of Vioxx (and similar drugs like Celebrex)
was that it might offer a benefit to arthritis sufferers who
couldn’t tolerate standard NSAIDs.
The problem is that blocking COX-1 also has cardiovascular
benefits, by lowering the incidence of blood clots. The dilemma
Merck faced in the mid 1990s was how to conduct clinical trials
to prove that Vioxx was gentler on the stomach, without highlighting
the fact that it might also increase cardiovascular risks.
Internal company documents suggest that Merck was well aware
that clinical trials might show significantly higher rates
of cardiovascular problems in patients taking Vioxx, as compared
to aspirin or other NSAIDs. A Merck email dated February 25,
1997, argued that unless patients taking Vioxx in clinical
trials also got aspirin “you will get more thrombotic
events (blood clots) and kill the drug.”
In 1999, Merck began a 3,000-patient trial of Vioxx called
the VIGOR (Vioxx GI Outcomes Research) study, comparing patients
on Vioxx with control patients taking naproxen. The Vioxx
patients did not take aspirin or other NSAIDs, so the study
was designed to highlight the GI benefits of Vioxx -- but
the study also excluded any patients who were at high risk
for cardiovascular problems.
The results of that study were published in March of 2000
and demonstrated significantly more blood clot-related problems
in the Vioxx group than in the controls taking naproxen, even
though patients who had appeared to be at risk were excluded
from the study. Specifically, the rate of heart attacks in
the Vioxx group was four times higher than in the naproxen
group.
Despite these early findings, Merck continued to claim that
Vioxx was safe. A Merck press release before the publication
of the VIGOR results in 2000 was headlined “Merck Confirms
Favorable Cardiovascular Safety Profile of Vioxx” and
claimed there was “NO DIFFERENCE in the incidence of
cardiovascular events” between Vioxx and NSAIDs.
When the VIGOR results were formally published in the New
England Journal of Medicine in November of 2000, the article
-- which was co-written by Merck employees -- discussed the
benefits of Vioxx for the stomach and assured doctors that
the difference in the rate of heart attack between Vioxx and
naproxen was “not significant.” After the FDA’s
own drug-safety office presented data in August 2004 showing
that Vioxx at high doses tripled the risk of heart attack
or sudden cardiac death, Merck issued a press release saying
that the company “strongly disagreed” with the
FDA’s analysis and that “Merck stands behind the
efficacy, overall safety and cardiovascular safety of Vioxx.”
But less than a month later, outside researchers working
on another study Merck had funded to see whether Vioxx might
lead to a reduction of polyps in the colon (APPROVe) asked
Merck to halt the study because patients on Vioxx were suffering
significantly more heart attacks than the control group after
18 months of exposure to the drug. It was only at that point
that Merck finally made the decision to recall the drug from
the market.
|
