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coxibs in cardiac surgery patients (NNH 73) (Elia et al, 2005 Level I). An analysis of the effects of
different coxibs on renal function showed that a COX‐2 inhibitor class effect was not evident as
rofecoxib was associated with an increased risk of renal dysfunction while celecoxib was not
(Zhang et al, 2006 Level I).
Platelet function
Platelets produce only COX‐1, not COX‐2, and as a corollary coxibs do not impair platelet
function (Munsterhjelm et al, 2006 Level II). The use of rofecoxib reduced surgical blood loss in
comparison with diclofenac (Hegi et al, 2004 Level II).
Cardiovascular effects
Information relating to the cardiovascular (CV) risks associated with the use of nsNSAIDs and
coxibs is derived from long‐term treatment data and may not reflect the risk of short‐term use
in the acute pain setting.
In a comparison of drug groups, there was no difference in the incidence of CV complications
with nsNSAIDs compared with coxibs (Moore et al, 2007 Level I). However, there may be
differences between different drugs in each class, although the evidence is conflicting.
One meta‐analysis failed to show any difference in the risk of CV events between celecoxib
and placebo or between celecoxib and nsNSAIDs (White WB et al, 2007 Level I) but another
concluded that the risk was less with celecoxib and valdecoxib compared with nsNSAIDs as a
group (Moore et al, 2007 Level I). Yet another study reported that coxibs were associated with a
moderate increase in the risk of CV events, as were high dose regimens of ibuprofen and CHAPTER 4
diclofenac, but not high doses of naproxen (Kearney et al, 2006 Level I). The American Heart
Association has identified naproxen as the preferred NSAID for long‐term use in patients with
or at high risk for cardiovascular disease (Antman et al, 2007).
A large case‐controlled study using a general practice database identified 9218 patients over
4 years with a ‘first ever’ diagnosis of myocardial infarction and compared them with matched
controls (Hippisley‐Cox & Coupland, 2005 Level III‐3). Where individual drugs were specified in the
results, the risks were significantly increased for patients using rofecoxib, diclofenac and
ibuprofen but not those taking celecoxib. Systematic reviews of case‐control and cohort
studies also found that celecoxib in commonly used doses may not increase the CV risk but
confirmed an increased risk with diclofenac and rofecoxib (Hernandez‐Diaz et al, 2006 Level I;
McGettigan & Henry, 2006 Level I).
An increase in the incidence of cerebrovascular and CV events in patients given parecoxib,
then valdecoxib after coronary artery bypass graft (CABG) surgery has also been reported
(Nussmeier et al, 2005 Level II). Therefore, their use is contraindicated after this type of surgery.
However, short‐term use of parecoxib and/or valdecoxib after non‐cardiac surgery does not
increase the risk of CV adverse events (Schug et al, 2009 Level I).
The FDA concluded that ‘Short‐term use of NSAIDs to relieve acute pain, particularly at low
doses, does not appear to confer an increased risk of serious adverse CV events (with the
exception of valdecoxib in hospitalized patients immediately postoperative from coronary
artery bypass surgery)’ (FDA, 2005).
It is possible that some nsNSAIDs may inhibit the protective effect of aspirin. Ibuprofen but not
diclofenac may abolish the benefits of aspirin (MacDonald & Wei, 2003 Level III‐3; Hudson et al,
2005 Level III‐3). The FDA issued a caution about the concomitant use of ibuprofen and
immediate‐release preparations (not enteric coated) of aspirin saying that ‘At least 8 hours
should elapse after ibuprofen dosing, before giving aspirin, to avoid significant interference’;
insufficient data were available to make any recommendations on the use of enteric coated
aspirin (FDA, 2006).
Acute pain management: scientific evidence 77