(2005; 12 pages)
CELECOXIB - Increased risk of cardiovascular events
Europe, New Zealand, USA. Pfizer has announced that the US National Cancer Institute Data Safety and Monitoring Board has stopped drug administration in the Adenoma Prevention with Celecoxib (Celebrex; APC) trial, as the risk of major cardiovascular events was significantly higher in patients receiving celecoxib than in patients receiving placebo. The US FDA and the EMEA have issued statements detailing the preliminary results, and have requested the full results for review(1-4).
In the APC study, 2400 patients received celecoxib 400 mg/day, celecoxib 800 mg/day or placebo, for a mean duration of 33 months. The relative risk (RR) of major fatal or nonfatal cardiovascular events (composite endpoint of cardiovascular death, acute myocardial infarction or stroke) was statistically significantly higher in the celecoxib 400 mg/day group (RR 2.5) and in the celecoxib 800 mg/day group (RR 3.4), compared with the placebo group.
Two other celecoxib trials, the Prevention of Spontaneous Adenoma Polyps (PreSAP) trial and the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT), have also been evaluated(4). The PreSAP trial has been stopped, based on the results of the APC trial, although an increased risk of cardiovascular events with celecoxib 400 mg/day compared with placebo was not observed(3). However, the ADAPT study is still ongoing(4).
The FDA has issued an Alert for Practitioners regarding the possible increased risk of cardiovascular events in patients receiving celecoxib(4).
Physicians are encouraged to inform patients of the evolving information about this risk, and are advised to consider alternatives to celecoxib; when this is not appropriate, the lowest effective celecoxib dose should be used. The New Zealand Medicines Adverse Reactions Committee has issued similar advice with regard to all COX-2 inhibitors, broadly supporting the UK National Institute of Clinical Excellence guidance that was distributed to all New Zealand general practitioners(5).
1. FDA Statement, 17 December 2004.Available on the Internet at www.fda.gov
2. EMEA Statement, EMEA/205831/2004, 17 December 2004. Available on the Internet at www.emea.eu.int
3. EMEA Statement, EMEA/212271/2004, 22 December 2004. Available on the Internet at www.emea.eu.int
4. FDA Alert for Practitioners (celecoxib), 17 December 2004. Available on the Internet at www.fda.gov
5. Medsafe Media Release, 21 December 2004. Available on the Internet at www.medsafe.govt.nz