Cristina Varas-Lorenzo, the corresponding author, ensures that all co-authors of the manuscript have materially and meaningfully contributed to the study and are, in public, able to speak of the work that has been done.
Version of Record online: 9 AUG 2006
Copyright © 2006 John Wiley & Sons, Ltd.
Pharmacoepidemiology and Drug Safety
Volume 16, Issue 4, pages 366–376, April 2007
How to Cite
Varas-Lorenzo, C., Maguire, A., Castellsague, J. and Perez-Gutthann, S. (2007), Quantitative assessment of the gastrointestinal and cardiovascular risk-benefit of celecoxib compared to individual NSAIDs at the population level. Pharmacoepidem. Drug Safe., 16: 366–376. doi: 10.1002/pds.1299
Conflict of interest: C. Varas, J. Castellsague, and S. Perez-Gutthann are Pfizer employees. A. Maguire was a Pfizer employee (Global Epidemiology, Barcelona, Spain) when this assessment was conducted.
- Issue online: 22 MAR 2007
- Version of Record online: 9 AUG 2006
- Manuscript Accepted: 24 JUN 2006
- Manuscript Revised: 8 JUN 2006
- Manuscript Received: 7 MAR 2006
- gastrointestinal and cardiovascular safety
To estimate the net cardiovascular (CV) (coronary heart disease, stroke, congestive heart failure), and gastrointestinal (GI) (peptic ulcer complications) risk-benefit public health impact of the use of celecoxib compared to non-selective NSAIDs in the arthritis population.
We applied discrete event simulation models to data from the US National Health Surveys, CV risk-prediction models from the Framingham Heart Study, and population-based studies. Models took into account the multifactorial effect of risk factors, comorbidity, and competing risk of mortality. We simulated the natural history of CV and GI disease in the U.S. arthritis population over 1 year, through the individual baseline cardiovascular and gastrointestinal risk profile. This model was modified with relative risks associated with the use of each treatment. The mean number of events was estimated for each end-point in each model: natural history, celecoxib, diclofenac, ibuprofen, naproxen. The number of events for celecoxib was compared with each NSAID.
The evaluation included 1% of the U.S. population with arthritis. Celecoxib, when applied to 100 000 patients over 1 year, resulted in 570 (range from sensitivity analysis: 440–691), 226 (124–313), and 746 (612–868) fewer ulcer complications than diclofenac, ibuprofen, and naproxen, respectively. There were 20 (16–25), 8 (4–12), and 27 (22–32) fewer deaths from ulcer complications, respectively. No increase in cardiovascular events or all cause mortality was observed for celecoxib versus the other individual NSAIDs.
Results from these simulations suggest a gastrointestinal benefit for celecoxib not offset by increased cardiovascular events or mortality. The methodology used here provides a risk-benefit assessment framework for evaluating the public heath impact of drugs. Copyright © 2006 John Wiley & Sons, Ltd.