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Letter to the Editor

Editor, – Regarding the article 'The vascular effects of COX-2 selective inhibitors' (Aust Prescr 2004;27:142-5), I agree that 'Low-dose aspirin or other anti-thrombotic treatment should be continued in patients receiving selective COX-2 inhibitors who are at risk of thrombosis'. However, one must ask why would we choose selective COX-2 inhibitors instead of conventional non-steroidal anti-inflammatory drugs (NSAIDs) for patients taking anti-platelet therapy?

In the CLASS study, patients who took celecoxib and aspirin (approximately 20% of nearly 8000 patients) had the same annualised incidence of symptomatic ulcers and upper gastrointestinal ulcer complications as patients taking aspirin with an NSAID (either ibuprofen 800 mg tds or diclofenac 75 mg bd).1 The literature suggests that the principal 'advantage' of upper gastrointestinal safety is lost when a COX-2 inhibitor is co-prescribed with aspirin.

Published reports also show that patients taking COX-2 inhibitors appear to have only slightly fewer upper gastrointestinal symptoms (such as dyspepsia) than patients treated with conventional NSAIDs.2

The COX-2 inhibitors have a substantial cost premium, but marginal safety advantages in some selected patients. With reference to your recent editorial 'Expensive new drugs - do we really need them?' (Aust Prescr 2004;27:136-7), the data would suggest that the COX-2 inhibitors are another example of expensive new drugs with an unclear cost-benefit value for the Pharmaceutical Benefits Scheme.

Paul Kubler
Rheumatologist/Clinical pharmacologist
Royal Brisbane Hospital & Royal Women's Hospital and Health Service Districts
Brisbane

Authors' comments

Professor R.O. Day and Professor G.G. Graham, authors of the article, comment:

Dr Kubler is correct in stating that, in the CLASS study, patients treated with celecoxib and aspirin had the same incidence of upper gastrointestinal complications as patients receiving the non-selective non-steroidal anti-inflammatory drugs (NSAIDs), diclofenac or ibuprofen. A similar result was found in the TARGET study of the COX-2 selective drug, lumiracoxib, versus naproxen or ibuprofen.3 It has, however, been suggested that a selective COX-2 inhibitor and low-dose aspirin should be used with a gastroprotective drug, such as a proton pump inhibitor or misoprostol, in patients at high risk of gastrointestinal damage, although the value of such combinations is presently unknown.4

The comparative effects of the COX-2 selective drugs and the non-selective NSAIDs on dyspepsia is a more difficult question because many patients in clinical trials note that they have dyspepsia even when they are taking placebo. Consequently, the occurrence of dyspepsia during treatment with the COX-2 selective inhibitors can only be evaluated from controlled clinical trials when placebo was administered.

It is therefore of note that the incidence of dyspepsia and related effects during treatment with celecoxib was very similar to that recorded during dosage with placebo, but markedly lower than during treatment with naproxen.5

References

  1. Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis: the CLASS study: a randomised controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA 2000;284:1247-55..
  2. Langman MJ, Jensen DM, Watson DJ, Harper SE, Zhao PL, Quan H, et al. Adverse upper gastrointestinal effects of rofecoxib compared with NSAIDs. JAMA 1999;282:1929-33.
  3. Schnitzer TJ, Burmester GR, Mysler E, Hochberg MC, Doherty M, Ehrsam E, et al. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), reduction in ulcer complications: randomised controlled trial. Lancet 2004;364:665-74.
  4. Chan FK, Graham DY. Review article: prevention of non-steroidal anti-inflammatory drug gastrointestinal complications - review and recommendations based on risk assessment. Aliment Pharmacol Ther 2004;19:1051-61.
  5. Bensen WG, Zhao SZ, Burke TA, Zabinski RA, Makuch RW, Maurath CJ, et al. Upper gastrointestinal tolerability of celecoxib, a specific COX-2 inhibitor, compared to naproxen and placebo. J Rheumatol 2000;27:1876-83.