Understanding the NSAID related risk of vascular eventsBMJ 2006; 332 doi: https://doi.org/10.1136/bmj.332.7546.895 (Published 13 April 2006) Cite this as: BMJ 2006;332:895
All rapid responses
We thank Dr. Haldane for his compliment and we agree with him that
for many patients the cardiovascular risk during the use of selective COX
2 inhibitors is small. We also share his personal experience that for some
patients Rofecoxib proved to be an effective pain killer for which they
are willing to sign a disclaimer.
However, while individual patients may prefer one NSAID over another,
in general, selective COX 2 inhibitors show equal efficacy in pain
management to non selective NSAIDs.
The risk for myocardial infarction and stroke during the use of selective
COX 2 inhibitors depends on the patients prior risk profile. As the post-
CABG studies demonstrate, in very high risk patients, cardiovascular
events can occur even during short term treatment. Selective COX 2
inhibitors were designed as a niche drug intended for patients at high
risk for gastrointestinal ulcer complications. Unfortunately, there is
considerable overlap between risk for gastrointestinal harm and risk for
cardiovascular harm. The relationship between selective COX 2 inhibitors
and cardiovascular harm cannot easily be mitigated; adding aspirin will
negate the sparing effect on gastrointestinal harm. Conversely, in the
prevention of NSAID attributable gastrointestinal harm alternatives exist
like adding misoprostol or proton pump inhibitors. Therefore, when
prescribing either NSAIDs or selective COX 2 inhibitors, physicians should
weigh cardiovascular risk and gastrointestinal risk and keep in mind the
different treatment options. Based upon the present data, patients at risk
for cardiovascular events should not (have to) be treated with selective
COX 2 inhibitors.
We agree that in the postoperative setting NSAIDs can be part of the
analgesic regime. But our warning is still valid: our data (unpublished)
in 420 hospitalised orthopaedic patients shows that 11% has heart failure
at admission and uses RAAS inhibitors with diuretics. Given the drug-drug
interaction between NSAIDs and RAAS inhibitors and diuretics, these
patients are at risk for deterioration of their heart failure in the
Harald E Vonkeman, Jacobus RBJ Brouwers, and Mart AFJ van de Laar
Competing interests: No competing interests
I would like to congratulate Dr Vokeman & his colleagues on an
excellent review of NSAID related risk of vascular events¹. However, as a
Consultant Anaesthetist with a special interest in peri-operative acute
pain management, I would like to raise a couple of points.
NSAIDs are very effective analgesics as part of a balanced analgesic
regime to manage post-operative pain. The introduction of COX 2 drugs
facilitated the use of this class of drugs in patients at risk of
gastrointestinal complications with conventional NSAID therapy in the post
-operative setting. COX 2 drugs have been proven to be less irritant to
the gastrointestinal tract & to my knowledge there is no evidence of
increased cardiovascular risk with short term peri-operative dosing
regimes with the exception of the coronary artery bypass model. This model
is not relevant to the majority of post-operative patients.
We are therefore denied access to a very effective group of analgesic
drugs with an appropriate clinical licence (Rofecoxib) for short term post
-operative use as a result of evidence of a small increased risk of
thrombotic events based on long term high dose therapy.
Also, Rofecoxib in particular had a very positive impact on the long
term management of pain in patients suffering from rheumatoid or osteo-
arthritic joint pain. The acute withdrawal of this drug was therefore
associated with the return of suffering in a large number of patients in
whom, Rofecoxib was often described as ‘the only pain killer’ to relieve
their symptoms & maintain mobility. I am personally aware of a number
of cases where this led to further morbidity and in one case to death.
While this case is anecdotal & extreme, the point that I wish to
make is that we should not extend evidence beyond the realms of proven
harm & that risk/benefit analogy may favour continued use. In
addition, in an era of informed consent, I wonder how many patients would
welcome the opportunity to sign a disclaimer stating that they were
willing to accept the small potential risks of a thrombotic event in the
future in favour of the real and sustained analgesia offered by COX2 drugs
with subsequent improvement in immediate mobility & quality of life,
not to mention the potential reduction in gastrointestinal morbidity.
1. Vonkeman HE, Brouwers JRBJ, Van de Laar MAFJ. Understanding the
NSAID related risk of vascular events. BMJ 2006;332:895-8.
Competing interests: No competing interests