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PRACTICE: Harald E Vonkeman, Jacobus R B J Brouwers, and Mart A F J van de Laar Understanding the NSAID related risk of vascular events BMJ 2006; 332: 895-898 [Full text]

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COX 2 Drugs - An alternative point of view.

Grant J Haldane   (27 April 2006)

Re: COX 2 Drugs - An alternative point of view.

Harald E. Vonkeman, Jacobus RBJ Brouwers, and Mart AFJ van de Laar   (10 May 2006)

COX 2 Drugs - An alternative point of view. 27 April 2006
Grant J Haldane, Consultant Anaesthetist Hairmyres Hospital, Eaglesham Road, East Kilbride. G75 8RG Send response to journal: Re: COX 2 Drugs - An alternative point of view.	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: None declared
Re: COX 2 Drugs - An alternative point of view. 10 May 2006
Harald E. Vonkeman, Rheumatologist Medisch Spectrum Twente Hospital and University of Twente, 7500KA, Enschede, the Netherlands, Jacobus RBJ Brouwers, and Mart AFJ van de Laar Send response to journal: Re: Re: COX 2 Drugs - An alternative point of view.	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 postoperative period. Harald E Vonkeman, Jacobus RBJ Brouwers, and Mart AFJ van de Laar Competing interests: None declared