Sept. 30, 2004 -- The pain reliever Vioxx is voluntarily
withdrawn from markets worldwide by the drug's maker, Merck & Co. The
decision follows news from a large clinical trial in which long-term use of the
drug (18 months or more) doubled participants' risk of heart attack and stroke.
Calling the risk "small" to any particular patient, the FDA says,
"We think Merck is doing the right thing."
Since Vioxx is a Cox-2 inhibitor drug, some people wonder if other drugs in
the same class (namely, Celebrex and Bextra) might have similar risks.
Dec. 9, 2004 - The FDA orders a new, bold-faced warning on
Bextra labels, cautioning that the drug should not be taken by patients
undergoing heart bypass surgery. The FDA also strengthens warnings about the
risk of serious, potentially fatal skin reactions to Bextra.
Dec. 17, 2004 -- A cancer-prevention study shows that
Celebrex more than doubled heart deaths, heart attacks, and strokes in people
enrolled. The National Cancer Institute stops the study. However, the affected
participants were taking twice the normal amount of Celebrex usually prescribed
Also, The New England Journal of Medicine publishes a letter by
Vanderbilt University researcher Wayne A. Ray, PhD, and colleagues questioning
Dec. 23, 2004 -- The FDA issues a public health advisory
about nonsteroidal anti-inflammatory drugs (NSAIDs) including Cox-2
The advisory says that "recently released data from controlled clinical
trials showing that the Cox-2 selective agents (Vioxx, Celebrex, and Bextra)
may be associated with an increased risk of serious cardiovascular events
(heart attack and stroke), especially when they are used for long periods of
time or in very high-risk settings (immediately after heart surgery)."
The advisory also says that long-term use of another NSAID, naproxen (sold
as Aleve, Naprosyn, and other trade or generic names) "may also be
associated with an increased cardiovascular risk, compared to placebo."
The National Institutes of Health had suspended the study that showed that
risk with naproxen. Later, the researchers said reports of naproxen's heart
effects were overblown and unnecessarily scared the public (see Feb. 18,
Jan. 18, 2005 -- Two new studies suggest that combining
Bextra with aspirin may increase the risk of blood clots that could trigger a
heart attack or stroke.
Jan. 24, 2005 - A study in the Archives of Internal
Medicine says Celebrex and Vioxx have been widely overused.
Jan. 31, 2005 -- Health insurance company Kaiser Permanente
says it will no longer offer Bextra, citing concerns that the drug's potential
benefits were not worth the potential risks.
Feb. 16, 2005 -- The FDA opens a federal inquiry into Cox-2
On the same day, Merck presents data suggesting that heart risks with Vioxx
do not show up until patients have taken the drug for at least 18 months.
Feb. 17, 2005 -- A previously undisclosed study presented
by an FDA safety officer says the most common dose of Celebrex (200 milligrams
per day) does not increase heart attack risk. "Above 200 milligrams, we
believe there is evidence of increased risk," FDA whistleblower David
Graham, MD, says. Pfizer, which markets Celebrex, says most studies did not
show an increased heart risk with their drug and that safety concerns appear to
be unique to Vioxx.
Graham also says an analysis suggests that Vioxx may cause heart attacks
much earlier than the 18 months mentioned in Merck's presentation a day
Several experts tell the FDA's advisory panel there's enough evidence to
suggest that Vioxx, Bextra, and Celebrex all raise the risk of heart attack and
Feb. 18, 2005 -- An FDA advisory panel says the arthritis
drug Vioxx can return to the market and that Celebrex and Bextra should remain
available -- with strict warnings that Cox-2 inhibitors can raise the risk of
heart attack and stroke.
The panel also recommends that labels for many of the more than 20 older
anti-inflammatory drugs be updated to warn consumers and doctors that they may
carry a heart risk. Three of those drugs -- ibuprofen, naproxen, and ketoprofen
-- are available over the counter.
The expert recommendations to go the FDA, which is not obligated to follow
them but generally does.
Also, Johns Hopkins University researcher Constantine Lyketsos, MD, tells
the panel that reports about naproxen (Aleve, Naprosyn, etc.) and heart attack
are overblown. Lyketsos, who worked on the study, says the drug's heart effects
were "barely significant." He says some participants became hesitant to
take their drugs in the wake of concerns about Vioxx and other drugs.
April 7, 2005 --The drug company Pfizer suspends sales of
Bextra after the FDA asks it to pull the drug off the market. Pfizer says it
disagrees with the FDA's request and hopes to reintroduce the drug later.
The FDA also asks Pfizer to include a boxed warning on the Celebrex label;
Pfizer agrees to work with the agency. The warning highlights the potential
risk of heart attack and stroke with Celebrex as well as the potential for
serious, life-threatening stomach ulcer bleeding.
In addition, the FDA asks makers of all NSAIDs to revise their labels to
include more specific information on potential heart and stomach ulcer bleeding
risks. The FDA also wants those drugs' labels to provide information to help
consumers use those drugs safely.
Makers of over-the-counter anti-inflammatory drugs are also asked by the FDA
to include a warning about potential heart and stomach ulcer bleeding