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Review
. 2002 Nov 12;167(10):1131-7.

The double-edged sword of COX-2 selective NSAIDs

James M Wright  1
Affiliations
Review

The double-edged sword of COX-2 selective NSAIDs

James M Wright. CMAJ. .

Abstract

The launch of the cyclooxygenase-2 (COX-2) selective NSAIDs was based on 2 hypotheses: (1) the major adverse effects limiting the usefulness of nonselective NSAIDs are gastrointestinal in nature and (2) COX-2 selective NSAIDs are associated with fewer gastrointestinal adverse effects than nonselective NSAIDs. At the time of the launch, neither of these hypotheses had been proven and, as documented in this review, both remain uncertain. The increased incidence of total and nongastrointestinal serious adverse events, with the COX-2 selective NSAIDs as compared with nonselective NSAIDs, in the Celecoxib Long-term Arthritis Safety Study (CLASS) and the Vioxx Gastrointestinal Outcomes Research (VIGOR) study remains a major concern. The increased morbidity associated with the COX-2 selective NSAIDs may be a manifestation of the COX-2 selectivity of rofecoxib and celecoxib or the supramaximal doses of these drugs used in the trials. Proof that the increased harm was not caused by the COX-2 selectivity of the drugs depends on demonstration in a randomized controlled trial that COX-2 selective NSAIDs at usual doses are as effective as nonselective NSAIDs and cause fewer gastrointestinal serious adverse events without increasing the incidence of total nongastrointestinal serious adverse events.

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Figures

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Fig. 1: Meta-analysis of relative risk of total mortality with cyclooxygenase-2 (COX-2) selective nonsteroidal anti-inflammatory drugs (NSAIDs) compared with nonselective NSAIDs in the Celecoxib Long-term Arthritis Safety Study (CLASS), and the Vioxx Gastrointestinal Outcomes Research (VIGOR) study., CI = confidence interval, FDA = US Food and Drug Administration. *Group that received COX-2 selective NSAIDs: number of participants who were affected/total number of participants. †Group that received nonselective NSAIDs: number of participants who were affected/total number of participants.
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Fig. 2: Meta-analysis of relative risk of serious adverse events (SAEs) (including death, admission to hospital, and any life- threatening event or event leading to serious disability) with COX-2 selective NSAIDs compared with nonselective NSAIDs in the CLASS, and the VIGOR study.,
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Fig. 3: Meta-analysis of relative risk of complicated ulcers with COX-2 selective NSAIDs compared with nonselective NSAIDs in the CLASS, and the VIGOR study.,
See this image and copyright information in PMC

Comment in

  • Seeking disclosure.
    Maksymowych WP. Maksymowych WP. CMAJ. 2003 Apr 15;168(8):960, 962; author reply 962. CMAJ. 2003. PMID: 12695369 Free PMC article. No abstract available.
  • COX-2 inhibitors and type 4 error.
    Pijak MR, Gazdik F. Pijak MR, et al. CMAJ. 2003 Aug 5;169(3):190. CMAJ. 2003. PMID: 12900475 Free PMC article. No abstract available.

References

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