Eradication of H. pylori Before NSAID Therapy to Prevent Peptic Ulcers
ABSTRACT & COMMENTARY
Synopsis: Eradication of H. pylori before initiation of NSAID therapy reduces the occurrence of NSAID-induced peptic ulcers.
Source: Chan FKL, et al. Randomized trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers Lancet 1997;350: 975-979.
Chan and associates studied the efficacy of eradication of Helicobacter pylori in the prevention of NSAID-induced peptic ulcers. Patients who had H. pylori infection but no pre-existing ulcers on endoscopy were randomly allocated to naproxen alone (750 mg daily) for eight weeks or to a one-week course of triple therapy (bismuth subcitrate 120 mg, tetracycline 500 mg, metronidazole 400 mg, each given orally qid) before administration of naproxen. Endoscopy was repeated after eight weeks of naproxen treatment or when naproxen treatment was stopped early because of bleeding or intractable dyspepsia. The primary end point was the cumulative rate of gastric and duodenal ulcers.
At eight weeks, H. pylori had been eradicated from 0% of the patients in the naproxen group and 89% of those in the triple therapy group. Twenty-six percent of the naproxen group patients developed ulcers, five had ulcer pain, and one developed ulcer bleeding. Only 7% of patients on triple therapy had ulcers, and two out of these three had failure of H. pylori eradication. Thus, 26% of patients with persistent H. pylori infection but only 3% with successful H. pylori eradication developed ulcers with naproxen. The authors conclude that eradication of H. pylori before NSAID therapy reduces the occurrence of NSAID-induced peptic ulcers.
COMMENT BY EAMONN M.M. QUIGLEY, MD
Infection with H. pylori and the consumption of NSAIDs are the two most important causes of gastroduodenal ulceration. Not surprisingly, these factors often coexist, and it has been suggested that H. pylori is present in about 50% of patients with NSAID-associated ulcer disease. Furthermore, it is evident that NSAID consumption is responsible for significant morbidity and mortality related to gastroduodenal ulceration, and several strategies have been proposed to minimize the risk of ulceration and complications such as bleeding and perforation related to NSAID use. Prospective clinical studies have demonstrated efficacy for H2-receptor antagonists, the prostaglandin analog misoprostol, and the proton pump inhibitor omeprazole. In this paper, the authors set out to examine what role H. pylori may play in NSAID-related ulcers and, specifically, to define whether eradication of H. pylori prior to NSAID use could reduce the prevalence of ulcers. The study demonstrates, pretty conclusively, a significant reduction in NSAID-related ulcers in those patients who have previously undergone eradication of Helicobacter pylori.
The study does have some limitations. First, it is relatively short term. Second, one could question the clinical significance of the primary end point, namely, the development of gastric and duodenal ulcers. In the context of NSAID-related mucosal disease prophylaxis, others have questioned the clinical relevance of this end point and stressed instead the importance of bleeding, perforation rates, and mortality rather than endoscopically defined ulcers. In support of their argument, Chan et al suggest that ulceration is, indeed, very common with a variety of NSAIDs but that it only becomes clinically relevant if the patients develop symptoms or complications such as bleeding, perforation, or even death. To address these issues, larger long-term prospective studies will be required. In this study, it seems not unreasonable to expect, however, that a positive effect of H. pylori eradication would be seen with these end points, also. In any event, this study provides strong evidence against another hypothesis, namely, that H. pylori infection may protect against NSAID-related injury. Postulating that Helicobacter infection may promote mucosal protection through inflammatory mediators and quoting somewhat indirect evidence from clinical studies, some have gone so far as to propose that H. pylori should not be eradicated in patients consuming NSAIDs. Based on this study, however, the recommendation for now should be to eradicate H. pylori when it coexists in the patient with NSAID-related mucosal injury or prior to initiating chronic NSAIDs. (Dr. Quigley is Chief, Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha.)
References
1. Gabriel SE, et al. Risks for serious gastrointestinal complications related to the use of non-steroidal anti-inflammatory drugs: A meta-analysis. Ann Intern Med 1991;115:787-796.
2. Loeb DS, et al. Long-term non-steroidal anti-inflammatory drug use in gastroduodenal injury: The role of Helicobacter pylori. Gastroenterol 1992;102:1899-1905.
It has been suggested that H. pylori is present in what percent of patients with NSAID-associated ulcer disease?
a. 20%
b. 35%
c. 50%
d. 75%
e. 5%
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