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Findings from COX 2 studies are released

BMJ 2005; 330 doi: https://doi.org/10.1136/bmj.330.7488.381-a (Published 17 February 2005) Cite this as: BMJ 2005;330:381

Rapid Response:

Cardiovascular side effect of selective COX-2 inhibitors: all or nothing.

On 30 September 2004 on the basis of the APPROVe (Adenomatous Polyp
Prevention On Vioxx) trial that showed an adverse cardiovascular side-
effect profile, rofecoxib (Vioxx™) was withdrawn from the market. After
more than 80 million patients had taken this medicine a relative small
trial revealed an already know side effect toxicity of rofecoxib. In fact
previously, also the VIGOR (Vioxx Gastrointestinal Outcomes Research)
trial revealed a significant increase of cardiovascular events in
patients taking rofecoxib compared with those receiving naproxen1. A
similar public health concern occurred about another coxib (valdecoxib),
which is used by 7 million patients worldwide2. Recently, the National
Institutes of Health (NIH) announced that it has suspended the use of COX-
2 inhibitor celecoxib (Celebrex™) for all participants in a large
colorectal cancer prevention clinical trial conducted by the National
Cancer Institute (NCI)3. The study, called the Adenoma Prevention with
Celecoxib (APC) trial, was stopped because analysis by an independent Data
Safety and Monitoring Board (DSMB) showed a 2.5-fold increased risk of
major fatal and non-fatal cardiovascular events for participants taking
the drug compared to those on a placebo. Considering that the rigor of
relatively small clinical trials has allowed us to find this problem,
several questions remain to be addressed and in particular, how could be
improved the efficacy of the post marketing surveillance? Which is the
cardiovascular side effect of the other selective COX-2 inhibitors
actually available in commerce?

REFERENCES

1. Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events
associated with selective COX-2 inhibitors. JAMA 2001;286(8):954-9.

Ray WA, Griffin MR, Stein CM. Cardiovascular toxicity of valdecoxib. N
Engl J Med 2004;351:2767.

Solomon SD, McMurray JJ, Pfeffer MA et al. Cardiovascular risk
associated with celecoxib in a clinical trial for colorectal adenoma
prevention. N Engl J Med 2005;352: Feb 15; [Epub ahead of print].

Competing interests:
None declared

Competing interests: No competing interests

25 February 2005
Alfredo Tartarone
oncologist
Gianpiero Romano, Raffaele Ardito, Giuseppina Gallucci, Nicola Di Renzo
Division of Medical Oncology and Hematology, Centro di Riferimento Oncologico della Basilicata (C.R.