Patients with a bleeding peptic ulcer not caused by Helicobacter pylori infection or non-steroidal anti-inflammatory drugs (NSAIDs) are at considerable risk of recurrent bleeding and death. Furthermore, acid-suppressive drugs do not protect these patients, according to the October issue of Clinical Gastroenterology and Hepatology.
Peptic ulcers that are not associated with H pylori infection or use of NSAIDs have distinct features from ulcers caused by H pylori infection, and account for a significant percentage of bleeding ulcers (see below figure).
These ‘H pylori–negative idiopathic bleeding ulcers’ are more likely to start bleeding again after treatment, and patients have higher mortality than those with other types of peptic ulcers. Some physicians use gastroprotective agents, such as proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs), to try to prevent repeat bleeding, but it is not clear if this approach is effective.
Grace Lai–Hung Wong et al. followed 663 patients with H pylori–negative idiopathic bleeding ulcers at the Prince of Wales Hospital, in Hong Kong, to determine if gastroprotective agents improved their outcomes.
After patients’ initial ulcers had healed, 566 of these patients received gastroprotective agents, at their doctor’s discretion; all patients were followed or an average of 32 months.
The incidence of recurrent ulcer bleeding did not differ significantly between groups of patients that did or did not receive gastroprotective agents. Nor was use of gastroprotective agents associated with mortality, after adjusting for confounders.
Wong et al. also followed patients with H pylori-positive ulcers who did not receive gastroprotective agents after eradication therapy.
They observed that incident rates of recurrent ulcer bleeding and death were significantly higher in patients with H pylori–negative idiopathic ulcers (2.9 and 17.0 per 100 person-years, respectively) than patients with H pylori–positive ulcers (1.1 and 5.9 per 100 person-years, respectively).
The authors conclude that H pylori–negative idiopathic bleeding ulcers are common, and account for about 12%–16% of all bleeding ulcers per year. Patients with these ulcers are at substantial risk of recurrent ulcer bleeding and death. Importantly, gastroprotective co-therapy does not protect them from recurrent bleeding of ulcers or death.
Because of the lack of protective effect of acid-suppressive drugs, higher doses of acid-suppressive agents or other agents, such as misoprostol might be alternatives. Unfortunately, the side effects of misoprostol include diarrhea, which might limit its use for these patients, who often have multiple comorbidities.
The authors point out that this was not a randomized trial, so that gastroprotective agents could have been preferentially prescribed to older and sicker patients. However, because of the relatively small number of patients with bleeding, H pylori–negative idiopathic ulcers, a large-scale randomized trial seems unfeasible.
So what causes H pylori–negative idiopathic ulcers? In selecting patients for the study, the authors ruled out use of other medications (such as potassium supplements, calcium channel blockers, and antidepressants), infections such as cytomegalovirus, inflammatory bowel disease, and other disorders (such as Zollinger–Ellison syndrome). More research is needed to identify causes of these ulcers.
The high recurrence of bleeding and mortality observed by Wong et al. could be related to old age and multiple comorbidities of the subjects. However, these factors are not likely to account for all these effects, because H pylori–negative idiopathic bleeding ulcer was an independent risk factor for rebleeding and mortality.
Other strategies are needed to prevent recurrent bleeding in patients with these unique ulcers.
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Lai–Hung Wong G, Wing–Lam Au K, Oi–Shan Lo A, et al. Gastroprotective therapy does not improve outcomes of patients with helicobacter pylori–negative idiopathic bleeding ulcers. Clin Gastroenterol Hepatol 2012;10:1124–1129.