Rapid Protection of the Gastroduodenal Mucosa Against Aspirin-induced Damage by Rabeprazole
Abstract & Commentary
By Malcolm Robinson, MD, FACP, FACG, Emeritus Clinical Professor of Medicine, University of Oklahoma College of Medicine, Oklahoma City. Dr. Robinson reports no financial relationship to this field of study.
Synopsis: The proton pump inhibitor rabeprazole is said to provide rapid acid inhibition, but clinical implications of this have been uncertain. This study shows that a single dose of rabeprazole 20 mg administered 5 hours before therapeutic dosing of aspirin significantly decreases gastroduodenal damage.
Source: S Irani, et al. Alimentary Pharmacology & Therapeutics. 2008;27:498-503.
Aspirin is known to induce gastric and duodenal submucosal hemorrhages and erosions, damage that can be prevented and/or healed by prophylactic or co-administration of potent acid blockers. The rapidity of onset of such protective effects using proton pump inhibitors (PPIs) had not been determined. Rabeprazole has been touted as having a particularly rapid onset, and the authors of this paper have previously documented acid inhibition within 2 ½ to 3 hours post-dosing and maximal acid inhibition by 5-6 hours. The present study was designed to evaluate gastric and duodenal mucosal damage in 30 normal subjects given either 20 mg of rabeprazole or placebo 5 hours before the initial administration of 650 mg of aspirin. Subjects had not taken any medications likely to injure or protect the upper GI mucosa in the month pre-study. Screening upper GI endoscopy had to be normal (no erosions or ulcerations) pre-study. The study protocol, initiated after an overnight stay and continuing housing in the Clinical Research Center at Temple University, involved one hour pre-breakfast administration of rabeprazole or placebo at 7 AM on days 1, 2, and 3. Breakfast was served to all subjected at 8 AM daily. Each subject received 2 tablets of 325 mg aspirin with 240 ml water every 4 hours between 8:30 AM and 4:30 AM each day throughout the 4 day study. Meals were standardized. Endoscopies were performed at 12 noon on days 2 and 4 (ie, 24 and 72 hours after the initiation of aspirin dosing). Submucosal hemorrhages and erosions were systematically quantified at each endoscopy to obtain standard Lanza scores. Maximum serum salicylate levels were comparable in both subject groups (maximum ca. 14 mg %). Global Lanza scores were significantly lower after rabeprazole administration than with placebo at 24 hours (1.3 ± 0.26 vs 2.1 ± 0.26, p < 0.05 and at 72 hours (1.3 ± 0.29 vs. 2.3 ± 0.28, p < 0.05). By chance, H. pylori was more common with rabeprazole than with placebo (5 infected vs 2 infected).
Commentary
This study certainly suggests that rabeprazole might be appropriate to prevent the earliest and later manifestations of gastroduodenal damage due to aspirin (and presumably other NSAIDs as well). Results would have been more compelling if an additional arm or arms had included one or more alternative PPIs. Rabeprazole does seem able to block aspirin-mediated damage after only a few hours, but we don't know that other ostensibly slow- er PPIs might not provide comparable benefits. In the current world of PPIs and potential future study designs,
such comparative studies seem unlikely to occur. The imbalance in H. pylori infection between the study groups might be significant in that the presence of this infection may potentiate aspirin and NSAID damage. Alternatively, it is also possible that infected individuals may have a differential response to PPI-mediated acid inhibition (eg, more responsive to such antisecretory effects). In retrospect, balancing the study for the presence or absence of H. pylori would have been betteror, best of all, if H. pylori positive subjects could have been eliminated. All in all, the results are provocative and could easily be the basis
for a broader clinical assessment. Since damage from aspirin and NSAIDs is likely to be greatest in the early phases of dosing, the availability of an antise- cretory agent capable of early damage prophylaxis would be potentially advantageous.
The proton pump inhibitor rabeprazole is said to provide rapid acid inhibition, but clinical implications of this have been uncertain. This study shows that a single dose of rabeprazole 20 mg administered 5 hours before therapeutic dosing of aspirin significantly decreases gastroduodenal damage.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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