Low-dose Aspirin and Endoscopic Gastric and Duodenal Ulcer Rates in Users of NSAIDs or COX-2 inhibitors
Low-dose Aspirin and Endoscopic Gastric and Duodenal Ulcer Rates in Users of NSAIDs or COX-2 inhibitors
Abstract & Commentary
By Malcolm Robinson, MD, FACP, FACG, Emeritus Clinical Professor of Medicine, University of Oklahoma College of Medicine, Oklahoma City. Dr. Robinson serves as a consultant for TAP, Pfizer, Janssen, Eisai, J&J-Merck, and Procter & Gamble, is on the speaker's bureau of Janssen, Eli Lilly, Solvay, TAP, and Aventis, and does research for Forest Labs, Wyeth-Ayerst, AstraZeneca, and Centocor.
Synopsis: Low-dose aspirin plus celecoxib led to ulcers in 19% of recipients vs 27% ulcers in patients receiving naproxen and low-dose aspirin. The group receiving low-dose aspirin plus placebo had 8% ulcer development.
Source: Goldstein, JL, et al. The impact of low-dose aspirin on endoscopic gastric and duodenal ulcer rates in users of a non-selective non-steroidal anti-inflammatory drug or a cyclo-oxygenase-2-selective inhibitor. Aliment Pharmacol Ther. 2006;23:1489-1498
Aspirin has well-documented anti-thrombotic effects and is extensively used in cardiovascular prophylaxis. However, 11% gastric and/or duodenal ulcer prevalence has been reported with low dose aspirin administration in the past, presumably due to aspirin's unfavorable impact on cyclooxygenase-1 (COX-1) in the gastric mucosa. Non-selective non-steroidal anti-inflammatory drugs (NSAIDs) are known to cause gastric and duodenal mucosal damage, and it is believed that aspirin worsens the propensity of non-selective NSAIDs to cause mucosal damage. COX-2 selective NSAIDs are thought to cause significantly fewer ulcers than COX-1 NSAIDs, but controversy continues regarding the risks associated with co-administration of COX-2 selective NSAIDs plus low-dose aspirin. The present 39-center study was done in 50-75 year old H. pylori-negative volunteers with normal baseline endoscopy. 450 subjects were ultimately evaluable. Of the evaluable group, 92 received 325 mg aspirin (ASA) plus placebo, 176 received naproxen 500 mg b.i.d. and ASA, and 182 evaluable subjects received celecoxib 200 mg daily plus ASA. Repeat endoscopy was performed after one week of the assigned therapy. Relative risk of gastric ulceration was highest with naproxen and aspirin at 3.3 (CI, 1.5-7.3) and numerically lower with celecoxib and aspirin at 2.7 (CI, 1.2-6.4). However, this difference was not statistically significant (P = 0.269). Duodenal ulcers, far less common in both groups, occurred in more naproxen plus ASA recipients than in the celecoxib plus ASA group (RR = 0.40; 95% CI, 0.17-0.94). Naproxen plus ASA was more likely to cause duodenal ulcers than ASA alone (RR 9.9; 95% CI, 1.2-83.9; P = 0.006). There was a numerical trend in the same direction for celecoxib plus ASA vs ASA alone (4.4% duodenal ulcers vs 1.1% duodenal ulcers, NS). Overall, celecoxib and ASA led to 18.7% combined gastric and duodenal ulcers vs 27.3% for naproxen and ASA vs 7.6% for ASA alone. Data for erosions of the mucosal paralleled the ulcer findings with even higher numbers for each of the respective groups.
Unlike some previous studies that suggested that ASA might totally negate the safety benefit of COX-2 administration, this study definitively demonstrates some improved safety (at least, in terms of endoscopic findings) with COX-2 plus ASA vs nonselective NSAID plus ASA. Nevertheless, as the authors point out, endoscopic differences may or may not directly translate to improved clinical safety.
Commentary
It seems to this reviewer that the take-home message from this study should be that danger lurks in administration of aspirin alone—and even more danger is associated with the combination of ASA and either selective or nonselective NSAIDs. High-risk patients (eg, those with severe co-morbidities) should probably avoid ASA and/or NSAIDs under most circumstances. The question that has been raised but not answered as yet is the potential for protection that might be afforded by co-administration of prostaglandins and/or proton pump inhibitors along with aspirin and COX-2 selective NSAIDS in some patients. Presumably such a study will ultimately be performed. In the meantime, many physicians will opt for such complex co-therapy in the hope that the known serious dangers of ASA and NSAIDs can be ameliorated.
Low-dose aspirin plus celecoxib led to ulcers in 19% of recipients vs 27% ulcers in patients receiving naproxen and low-dose aspirin. The group receiving low-dose aspirin plus placebo had 8% ulcer development.Subscribe Now for Access
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