1529-0131/asset/cover.gif?v=1&s=104d5c2bb8ef72deba26790b855af7ab80697a0e "Arthritis & Rheumatism")
Ms Massó González and Dr. Patrignani contributed equally to this work.
1529-0131/asset/olbannerleft.gif?v=1&s=897b81612b4ad6cae003112184adc709261d5f61)
1529-0131/asset/olbannerright.gif?v=1&s=04654f5ea3cbb01656383e0c0d04b16fd0a9a896)
Rheumatoid Arthritis Clinical Studies
You have full text access to this OnlineOpen article
Variability among nonsteroidal antiinflammatory drugs in risk of upper gastrointestinal bleeding
Article first published online: 22 FEB 2010
DOI: 10.1002/art.27412
Copyright © 2010 by the American College of Rheumatology
Additional Information
How to Cite
Massó González, E. L., Patrignani, P., Tacconelli, S. and Rodríguez, L. A. G. (2010), Variability among nonsteroidal antiinflammatory drugs in risk of upper gastrointestinal bleeding. Arthritis & Rheumatism, 62: 1592–1601. doi: 10.1002/art.27412
- ‡
Ms Massó González and Dr. Patrignani contributed equally to this work.
- §
Dr. García Rodríguez has received consulting fees from AstraZeneca (less than $10,000) and research grants from Novartis and Bayer.
Publication History
- Issue published online: 28 MAY 2010
- Article first published online: 22 FEB 2010
- Accepted manuscript online: 22 FEB 2010 12:00AM EST
- Manuscript Accepted: 12 FEB 2010
- Manuscript Received: 12 AUG 2009
Funded by
- European Community's Sixth Framework Program (Eicosanox). Grant Number: LSMH-CT-2004-005033
- Real Colegio Complutense at the Harvard School of Public Health
Abstract
Objective
Traditional nonsteroidal antiinflammatory drugs (NSAIDs) increase the risk of upper gastrointestinal (GI) bleeding/perforation, but the magnitude of this effect for coxibs in the general population and the degree of variability between individual NSAIDs is still under debate. This study was undertaken to assess the risk of upper GI bleeding/perforation among users of individual NSAIDs and to analyze the correlation between this risk and the degree of inhibition of whole blood cyclooxygenase 1 (COX-1) and COX-2 in vitro.
Methods
We conducted a systematic review of observational studies on NSAIDs and upper GI bleeding/perforation published between 2000 and 2008. We calculated pooled relative risk (RR) estimates of upper GI bleeding/perforation for individual NSAIDs. Additionally, we verified whether the degree of inhibition of whole blood COX-1 and COX-2 in vitro by average circulating concentrations predicted the RR of upper GI bleeding/perforation.
Results
The RR of upper GI bleeding/perforation was 4.50 (95% confidence interval [95% CI] 3.82–5.31) for traditional NSAIDs and 1.88 (95% CI 0.96–3.71) for coxibs. RRs lower than that for NSAIDs overall were observed for ibuprofen (2.69 [95% CI 2.17–3.33]), rofecoxib (2.12 [95% CI 1.59–2.84]), aceclofenac (1.44 [95% CI 0.65–3.2]), and celecoxib (1.42 [95% CI 0.85–2.37]), while higher RRs were observed for ketorolac (14.54 [95% CI 5.87–36.04]) and piroxicam (9.94 [95% CI 5.99–16.50). Estimated RRs were 5.63 (95% CI 3.83–8.28) for naproxen, 5.57 (95% CI 3.94–7.87) for ketoprofen, 5.40 (95% CI 4.16–7.00) for indomethacin, 4.15 (95% CI 2.59–6.64) for meloxicam, and 3.98 (95% CI 3.36–4.72) for diclofenac. The degree of inhibition of whole blood COX-1 did not significantly correlate with RR of upper GI bleeding/perforation associated with individual NSAIDs (r2 = 0.34, P = 0.058), but a profound and coincident inhibition (>80%) of both COX isozymes was associated with higher risk. NSAIDs with a long plasma half-life and with a slow-release formulation were associated with a greater risk than NSAIDs with a short half-life.
Conclusion
The results of our analysis demonstrate that risk of upper GI bleeding/perforation varies between individual NSAIDs at the doses commonly used in the general population. Drugs that have a long half-life or slow-release formulation and/or are associated with profound and coincident inhibition of both COX isozymes are associated with a greater risk of upper GI bleeding/perforation.