Further evidence that even commonly used nonsteroidal anti-
inflammatory drugs (NSAIDs) are harmful to heart-failure patients has
come from a new study [1].

The study, published in the January 26, 2009 issue of the Archives of
Internal Medicine, shows dose-related increases in risk of death and
rehospitalization for heart failure or MI with all COX-2 inhibitors
or other NSAIDs.

Lead author Dr Gunnar Gislason (Gentofte University Hospital,
Hellerup, Denmark), commented to heartwire: "Although our study is
observational, and you can never exclude all confounding factors, we
have very consistent results estimated using two different
statistical methods. And these results are similar to many other
previous studies. In addition, we see a strong dose-related response.
I think the data are very convincing."

And it is not just the COX-2 inhibitors that are the problem, as
diclofenac showed a similar risk. "This is very disturbing, as this
drug is so widely used and is available off prescription in many
countries," Gislason noted.

He described the effect as "quite considerable." For example, for
rofecoxib (Vioxx, Merck), the number of patients needed to treat for
one year to cause one death was just nine, and the corresponding
number for celecoxib (Celebrex, Pfizer) was 14 and diclofenac
11. "These numbers are very low," Gislason said, noting that for
antihypertensive drugs, the number needed to treat for one year to
save one life is in the range of 50 to 100. "Everyone agrees that it
is worth treating hypertension. So the harmful effect of some NSAIDs
is much greater than the beneficial effect of antihypertensive
treatment."

Even Naproxen Risky at High Dose

"Our results suggest that all NSAIDs have harmful effects in heart-
failure patients, even naproxen at high doses. Naproxen is probably
the best of the bunch, but it still increases fluid retention, which
is bad news for heart-failure patients," Gislason added.

But he points out that these drugs are still being used in this
population. "I don't think doctors are aware of this problem. We need
to raise awareness. I think the main culprits are primary-care
doctors, as these drugs are so widely prescribed in general
practice," he commented. "The fact that some of these drugs are
available over the counter makes the situation much worse, as anyone
can buy them without advice from a doctor. All NSAIDs should be
prescription-only drugs. Making them available in petrol stations and
supermarkets gives the impression that they are not harmful. Many
heart-disease patients will not be aware that they shouldn't take
them."

In the current study, Gislason and colleagues used Danish national
records of hospitalizations and pharmacy drug dispensing to identify
107 092 patients surviving their first hospitalization due to heart
failure between 1995 and 2004 and their subsequent use of NSAIDs.

They found that 36 354 patients (33.9%) claimed at least one
prescription of an NSAID after discharge; 60 974 patients (56.9%)
died, and 8970 (8.4%) and 39 984 (37.5%) were rehospitalized with MI
or heart failure.

After adjustment for age, sex, calendar year, comorbidity, medical
treatment, and severity of disease, the authors found a clear dose-
related increase in risk with the drugs.

The authors conclude that patients with heart failure should, if
possible, avoid using NSAIDs, and if they do need to use one, they
should take an agent that is more COX-1 selective, in as low a dosage
and for as short a period as possible. "I know NSAIDs are useful
drugs, and they will always be used to some extent, but we need to be
careful about which drug is selected and which dosage used. More
thought should go into trying to combine them with other agents so
that a lower dose could be used," Gislason added.


Gislason GH, Rasmussen JN, Abildstrom SZ, et al. Increased mortality
and cardiovascular morbidity associated with use of nonsteroidal anti-
inflammatory drugs in chronic heart failure. Arch Intern Med 2009;
169:141-149. Abstract