In a recent Canadian Adverse Reaction Newsletter1 issued by Health Canada, the authors recommend that “caution should be exercised in prescribing [selective COX-2 inhibitors] to patients at risk of cardiovascular disease.” To make such a recommendation based on the adverse reactions presented in the newsletter is not scientifically rigorous. The data are not adjusted for exposure, and thus are unlikely to represent an accurate evaluation of cardiovascular risk.
The impetus behind this article appears to be a meta-analysis by Mukherjee and colleagues,2 which is methodologically flawed3,4,5 and does not form an appropriate basis for public health recommendations.
Certainly the increased rate of adverse cardiovascular events, as demonstrated in the VIGOR study for rofecoxib,6 warrants further investigation. Clinical data available for celecoxib, however, demonstrate that patients on celecoxib are no more at risk of cardiovascular events than patients taking traditional NSAIDs such as ibuprofen, diclofenac or naproxen.7 This observation holds true even at supratherapeutic doses, as demonstrated in the CLASS trial.8,9
Differences in molecular structure and metabolism may partly explain the distinct cardiovascular safety profiles of the 2 coxibs, and this hypothesis should be examined further.10,11
If immediate recommendations are required, perhaps Health Canada would be more justified in suggesting that caution be exercised in prescribing these agents, particularly rofecoxib, to patients at high risk of cardiovascular disease. The implementation of such a policy should be individualized at the discretion of the treating physician in light of each patient's risk factor profile, the presence (if any) of diabetes and cardiovascular history.
John C. Peterson Cardiologist Toronto, Ont.
Competing interests: Dr. Peterson has spoken for the last 2 years at continuing medical education events for Novartis, Merck, Pharmacia and Abbott.
References
- 1.↵
Vu D, Murty M, McMorran M. Selective COX-2 inhibitors: suspected cardiovascular/cerebrovascular adverse reactions. Can Adverse React Newsl 2002;12(2):2-3.
- 2.↵
Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA 2001;286:954-9.
- 3.↵
Haldey EJ, Pappagallo M. Cardiovascular events and COX-2 inhibitors [letter]. JAMA 2001;286 (22): 2809-10.
- 4.↵
Singh G. Cardiovascular events and COX-2 inhibitors [letter]. JAMA 2001;286(22):2810-1.
- 5.↵
White WB, Whelton A. Cardiovascular events and COX-2 inhibitors [letter]. JAMA 2001;286 (22): 2811-2.
- 6.↵
Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 2000;343 (21): 1520-8, 2 p following 1528.
- 7.↵
Celebrex product monograph.
- 8.↵
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 and rheumatoid arthritis: the CLASS study: a randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA 2000;284(10): 1247-55.
- 9.↵
White WB, Faich G, Whelton A, Maurath C, Ridge NJ, Verburg KM, et al. Comparison of thromboembolic events in patients treated with celecoxib, a cyclooxygenase-2 specific inhibitor, versus ibuprofen or diclofenac. Am J Cardiol 2002; 89(4):425-30.
- 10.↵
Zhao S, Reynolds M, Lefkowith JL, Whelton A, Arellano FM. Comparison of cardiovascular and renal adverse drug reactions (ADRs) between rofecoxib and celecoxib based on the WHO/UMC safety database. Clin Ther 2001;23(9):1478-91.
- 11.↵
Whelton A, Fort JG, Puma JA, Normandin D, Bello AE, Verburg KM. Cyclooxygenase-2-specific inhibitors and cardiorenal function: a randomized controlled trial of celecoxib and rofecoxib in older hypertensive osteoarthritis patients. Am J Ther 2001;8:85-95.