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Senior Citizen Health & Medicine
COX-2, NSAID Can Spell DEATH for Recovering Heart
Attack Patients
After heart attack people
may be more
vulnerable to the harmful effects
 June 20, 2006 - After a heart attack, patients may
be at higher risk of death if they are treated with pain killers in a
drug class known as COX-2 inhibitors or with high doses of other
non-steroidal anti-inflammatory drugs (NSAIDs), according to a large
review published in Circulation: Journal of the American Heart
Association.
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Health & Medicine |
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Danish researchers analyzed the occurrence of death
or rehospitalization with another heart attack related to the use of
NSAIDs, including selective cyclo-oxygenase-2 (COX-2) inhibitors and
non-selective non-aspirin NSAIDs, among heart attack survivors.
Their analysis found that higher death rates were
associated with taking any NSAID compared to patients not taking NSAIDs,
and death rates were highest among those taking COX-2 drugs and high
doses of non-selective NSAIDs.
Patients who have already suffered a heart attack
appear to be more vulnerable to the harmful effect of these
medications, says Gunnar H. Gislason, M.D., lead author and senior
resident at Gentofte University Hospital in Copenhagen, Denmark.
In recent years, evidence has shown that patients
treated with selective COX-2 inhibitors have an increased risk of heart
attack and death. This study examined the risk specifically among
heart attack survivors, a population that is generally older and at a
high risk for future cardiovascular events.
COX-2 inhibitors are used primarily to treat pain
and arthritis in patients at risk of gastrointestinal bleeding.
Aspirin was not evaluated in the study, however there is strong evidence
that its use can prevent recurrent heart attacks.
We presume that more than 90 percent of people in
the study both those receiving NSAIDS and those not were taking
aspirin. People should continue to take low-dose aspirin for its clear
beneficial effect in preventing heart attack, Gislason said.
Researchers used the extensive national databases
in Denmark to link information on hospitalizations, prescriptions and
deaths. They examined records in the Danish National Patients Registry
on 58,432 men and women discharged from the hospital between 1995 and
2002 after a first heart attack. Researchers tracked prescriptions of
selective COX-2 inhibitors and other NSAIDS after discharge, their
dosages, and how long they were prescribed.
At some point after leaving the hospital, 17.5
percent of patients were treated at least once with the non- selective
NSAID ibuprofen (such as Motrin); 12.7 percent with other prescription
NSAIDS; 10.6 percent with the NSAID diclofenac (Cataflam and Voltaren);
5.2 percent with COX-2 inhibitor rofecoxib (Vioxx), and 4.3 percent with
COX-2 inhibitor celecoxib (Celebrex).
During the follow-up period, 9,773 patients
experienced a second heart attack and 16,573 died from any cause.
Compared to patients not taking any of these drugs,
the risk of death was:
● About two to three times higher for patients
taking low-dose rofecoxib (25 milligrams [mg] or less a day) or
celecoxib (200 mg or less a day);
● More than five-fold higher for patients taking
high-dose rofecoxib (more than 25 mg daily);
● Almost five-fold higher among those taking
high-dose celecoxib (more than 200 mg daily);
● More than four times higher for those on
high-dose diclofenac (more than 100 mg daily); and
● More than two times greater for those taking
high-doses ibuprofen (more than 1200 mg daily).
It was clear that higher doses were associated
with a higher risk of death. We looked to see whether patients
receiving these medications had more chronic illnesses than other
patients, perhaps leading to the higher death rates, but we found that
the patients were very similar in terms of their baseline
characteristics, Gislason said.
The results also indicated that a patient need not
take NSAIDs for a long period of time to be at heightened risk.
In an accompanying editorial, Judith S. Hochman,
M.A., M.D., and Nirav R. Shah, M.D., M.P.H., of New York University
School of Medicine noted, Although some uncertainty about the magnitude
of risk of NSAIDs persists, the study by Gislason et al contributes to
the growing body of evidence that there is risk associated with both
COX-2 inhibitors and non-selective, non-aspirin NSAIDs, suggesting that
we temper our use of all NSAIDs, weighing risk vs. benefit.
Gislason advises heart attack survivors that they
should discuss NSAID use with their physician.
If you have had a heart attack and are taking
NSAIDs, ask your doctor whether there might be other options for
treating your pain and other symptoms, Gislason said.
Likewise, Hochman and Shah caution that, in heart
disease patients, NSAIDs , if used, should be taken at the lowest
effective dose, for the shortest amount of time necessary, in
conjunction with low-dose aspirin and accompanied by a proton pump
inhibitor (PPI) medications that prevent the release of acid in the
stomach and intestines if warranted in a particular patient. In
regards to cardiovascular risk, aspirin (up to 1500 mg/day) appears to
be a safer anti-inflammatory agent, but PPIs may need to be added to
lower the risk of gastrointestinal bleeding.
To better understand these results, the research
team is analyzing death certificates to see what (if any) causes of
death were more common in patients taking the NSAIDS.
Co-authors are: Sψren Jacobsen, M.D., D.M.Sc.;
Jeppe N. Rasmussen, M.D.; Sψren Rasmussen, M.Sc., Ph.D.; Pernille Buch,
M.D.; Jens Friberg, M.D., Ph.D.; Tina Ken Schramm, M.D.; Steen Z.
Abildstrom, M.D., Ph.D.; Lars Kψber, M.D., D.M.Sc.; Mette Madsen, M.Sc.,
and Christian Torp-Pedersen, M.D., D.M.Sc.
The study was funded by a research fellowship from
the Danish Heart Foundation and an independent research grant from the
Danish Pharmaceutical Association.
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