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Interaction with NSAIDs

An observational study has suggested that regular use of NSAIDs (for more than 60
days per year) may abolish the cardioprotective effects of low-dose aspirin (1). A
second observational study found that, among 7107 individuals discharged from
hospital with diagnosed cardiovascular disease and prescribed low-dose aspirin
(<325mg/day), regular use of ibuprofen was associated with an increased risk of
death compared with use of aspirin alone (2). Other NSAIDs, including diclofenac,
were not associated with an increased risk.
On the basis of a laboratory study (3), it has been suggested that ibuprofen may
compete with aspirin for its binding site on the enzyme cyclo-oxygenase 1 (COX-1)
enzyme. Aspirin binds irreversibly to this site whereas ibuprofen does not. Aspirin is
rapidly metabolised so there is a relatively small period when it binds to the enzyme.
If ibuprofen is present during this period, it may interfere with aspirin binding and
therefore reduce the suppresion of platelet function.
Although these data appear to support an interaction between aspirin and ibuprofen,
the balance of evidence suggests that the outcome is not clinically significant (4).
These reviewers therefore suggested that advice to avoid ibuprofen in patients taking
low-dose aspirin for prevention of ischaemic heart disease is premature.
In a nested case-control study, 4,975 cases of acute myocardial infarction and death
from ischaemic heart disease were matched with 20,000 controls and their use of
NSAIDs was compared (5).The odds ratio (OR) for current NSAID use (including
ibuprofen) compared with non-use was 1.07 (95% CI, 0.95 - 1.20). Similar results
were found for the use of ibuprofen and aspirin at the same time compared with
aspirin alone (OR 1.10, CI95% 0.89 - 1.37). Treatment duration or daily dose did not
change the results and there was no difference between individual NSAIDs. The
reviewers therefore concluded that there was no clinically meaningful interaction
between low-dose aspirin and NSAIDs, including ibuprofen.
Most recently, the European Medicines Agency has reviewed the cardiovascular
safety of all non-COX selective NSAIDs such as ibuprofen (6). It found that the
evidence from clinical trials is inadequate to assess a possible risk. Observational
studies are, overall, inconclusive though an interaction between ibuprofen and aspirin
cannot be ruled out. It does not mention data from spontaneous reports. A clinically
important effect has not been clearly demonstrated.
The possibility of an interaction between naproxen and aspirin is also of concern. It
has been suggested that naproxen itself may be cardioprotective, leading to its use in
patients with arthritis and cardiovascular disease who need to take aspirin. A
laboratory study has shown that naproxen reduces the inhibitory effects of aspirin on
platelet function and COX-1 activity and this might reduce aspirin's cardioprotective
effect (7). The interaction between these two agents is complex and more clinical
trials are needed to establish the cardiovascular risks and benefits of available pain
The evidence regarding a clinically significant interaction between low-dose aspirin
and ibuprofen (or other NSAIDs) is therefore inconclusive. However, it may be
prudent for patients at high risk who take low-dose aspirin for cardioprotection to
avoid the use of ibuprofen for chronic pain relief.


1. Kurth T et al. Inhibition of clinical benefits of aspirin on first myocardial infarction by
nonsteroidal anti-inflammatory drugs. Circulation 2003;108:1191-1195
2. MacDonald TM, Wei L. Effect of ibuprofen on cardioprotective effect of aspirin.
Lancet 2003;361:573-574
3. Catella-Lawson F et al. Cyclooxygenase inhibitors and the antiplatelet effects of
aspirin. N Engl J Med 2001;345:1809-1817
4. Cheema AA. Should people on aspirin avoid Ibuprofen? A review of the literature.
Cardiol Rev. 2004 May-Jun;12(3):174-176
5. Garcia Rodriguez LA et al. Nonsteroidal antiinflammatory drugs and the risk of
myocardial infarction in the general population. Circulation. 2004 Jun
6. Medicines and Healthcare Products Regulatory Agency. Cardiovascular safety of
non-steroidal anti-inflammatory drugs. Overview of key data.
(; accessed 3.8.05)
7. Capone ML et al. Pharmacodynamic interaction of naproxen with low-dose aspirin
in healthy subjects. J Am Cull Cardiol 2005;45:1295-1301.
Updated November 2005


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Microsoft word - ch0119559125_en.doc

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