CLINICAL QUESTION: Will eradication of Helicobacter pylori improve the symptoms of nonulcer dyspepsia?
BACKGROUND: Although H pylori is associated with peptic ulcer disease, chronic gastritis, and other syndromes, its role in nonulcer dyspepsia is much more controversial. A recent meta-analysis suggested that there may be some benefit to H pylori eradication in nonulcer dyspepsia, but it did not include 2 recent studies with negative results.1 The authors of this study performed the first large multicentered randomized trial in the United States to evaluate the efficacy of H pylori eradication in nonulcer dyspepsia.
POPULATION STUDIED: Consecutive adult patients were invited to participate if they had at least moderate pain or discomfort in the upper abdomen for at least 3 months. Subjects all had a normal esophagogastroduodenal endoscopy (EGD) and a positive result on a carbon-13 urea breath test for H pylori. The average age was 46 years, and the other demographic characteristics were reasonably representative of the general population. Of the 640 patients screened, 337 were enrolled. Most of the exclusions were because patients did not have H pylori or had other underlying conditions.
STUDY DESIGN AND VALIDITY: This was a randomized multicenter trial. Patients were randomly assigned to receive either omeprazole 20 mg, amoxicillin 1000 mg, or clarithromycin 500 mg twice daily for 2 weeks, or identical placebos. In their power analysis, the authors calculated that 270 patients would provide an 88% chance of detecting a 20% reduction in symptoms. Overall, the methods of this study were appropriate to answer this particular question.
OUTCOMES MEASURED: The primary outcome reported was successful treatment (defined by the presence of no more than mild symptoms of dyspepsia during the previous week). Patients completed symptom diaries and the validated Gastrointestinal Symptom Rating Scale at baseline and 1, 3, 6, 9, and 12 months after enrollment. The urea breath test was repeated at the first return visit, and all patients had a repeat EGD and urea breath test at the end of the study (1 year). Quality of life was measured at enrollment and the end of the study using the Medical Outcomes Study Short Form-36 survey instrument.
RESULTS: With respect to the primary outcome, 46% of the patients in the intervention group had successful treatment compared with 50% in the control group (absolute difference = -4%; 95% confidence interval [CI], -15 to 8). Treatment was well tolerated and compliance was excellent in both groups. The absolute difference between groups for complete resolution of dyspeptic symptoms was 5% (95% CI, -5 to 15). There was no significant difference in quality-of-life scores. Not surprisingly, subjects in the intervention group did have a substantial reduction in the presence of H pylori.
The results of this well-done study suggest that there is no benefit to treatment of H pylori in patients with nonulcer dyspepsia. Two other recent studies support this conclusion.2,3 Unfortunately, these studies do not answer the more crucial primary care question: What is the appropriate diagnostic and therapeutic approach for patients with dyspepsia? Dyspepsia is a very common problem, and it would be very expensive to image the upper gastrointestinal tract on all dyspeptic patients. All patients enrolled in these studies were found not to have ulcer disease or cancer. In addition, none of these studies have followed patients for more than 12 months. Therefore, we do not know if there is benefit to long-term eradication of H pylori (such as reduction of risk of cancer or serious peptic ulcer disease). In dyspeptic patients who do not have ulcers or gastric cancer, it is unlikely that the elimination of H pylori will significantly improve their symptoms. Whether empiric eradication of H pylori will benefit patients presenting with undifferentiated dyspepsia remains unknown.