In the June 2001 issue of The Journal of Family Practice, the diagnostic approach to the patient with dyspepsia was presented.1 In that analysis, gastroesophageal reflux disease (GERD), gastric ulcers, and duodenal ulcers emerged as the most common identifiable causes of dyspepsia. However, most patients with dyspepsia do not have one of these conditions, and are considered to have functional or nonulcer dyspepsia. The diagnosis and management of adults with GERD was recently described in detail.2 Therefore, this paper reviews the treatment of undifferentiated dyspepsia, gastric ulcer caused by nonsteroidal anti-inflammatory drugs (NSAIDs), peptic ulcer disease not associated with NSAID use, and nonulcer dyspepsia (dyspepsia in a patient who has no evidence of ulcer or GERD on endoscopy). An algorithm for the management of the patient with known ulcer disease is shown in the Figure 1. (J Fam Pract 2001; 50:614-619)
Undifferentiated dyspepsia
In primary care, the typical patient presenting with dyspepsia will not have had endoscopy. Therefore, the presence of an underlying lesion will be unknown, a situation known as undifferentiated dyspepsia. As described by Smucny,2 randomized trials and economic analyses have demonstrated the cost-effectiveness of a test-and-treat strategy3,4 in which patients with dyspepsia are tested for Helicobacter pylori and treated with eradication therapy if positive. This strategy would reserve endoscopy for those patients with alarm signs Table1 or those who have persistent symptoms despite appropriate empiric therapy. Certainly a physician must weigh the potential for complications during endoscopy with the risks of adverse reactions to eradication therapy, including the development of antimicrobial resistant organisms. All patients with dyspepsia should be counseled to avoid factors that exacerbate their symptoms or disrupt the integrity of the mucosal lining of the stomach, such as NSAID use and cigarette smoking. Both of these have been identified as risk factors for the development of peptic ulcers and delayed ulcer healing.5,6
NSAID-related gastric ulcers
NSAIDs are associated with a 5- to 7-fold increased risk of gastric ulceration in the first 3 months of use. In a meta-analysis of observational studies of gastrointestinal bleeding risk due to various NSAIDs, a 4-fold increased risk associated with NSAID-use persisted throughout therapy and fell to baseline within 2 months of discontinuation of the NSAID.7 This study demonstrated a clear dose-response relationship; the difference between NSAIDs, however, was minimal.
Table 2 summarizes treatments for NSAID-related gastric ulcers. Misoprostol is an effective prophylaxis against ulcers when used with NSAIDs, but is associated with diarrhea, even at lower than optimal doses.8 Standard doses of H2-receptor agonists (H2RAs) are ineffective at preventing NSAID-related gastric ulcers, but double doses of H2RAs (eg, ranitidine 300 mg twice daily) and standard doses of proton-pump inhibitors (PPIs; eg, omeprazole 20 mg 4 times per day) are effective prophylactic agents for the duration of NSAID use according to the results of endoscopic studies. New COX-2 specific anti-inflammatory agents are associated with a significantly lower risk of ulcers as seen by endoscopy (4.7% with rofecoxib vs 27.7% with ibuprofen).9 The benefit in terms of actual adverse clinical outcomes and ulcer complications, however, is much smaller; the risk of symptomatic ulcer, perforation, symptomatic ulcer, and clinically significant bleeding was 1.3% for rofecoxib (Vioxx) and 1.8% with ibuprofen, diclofenac, or nabumetone taken for 1 year (P <.05).10 Thus, one would have to treat 200 patients for 1 year to prevent 1 adverse outcome. Similarly, the annual risk of bleeding, perforation, or gastric outlet obstruction was lower with celecoxib (Celebrex) than with naproxen, diclofenac, or ibuprofen (0.2% vs. 1.68%; P <.002; number needed to treat=60).11 COX-2 inhibitors have not been studied as an alternative therapy in patients with a history of NSAID-induced ulcers. While no trial data are available, a consensus-based recommendation has been made for dyspeptic patients with no alarm symptoms who are regular NSAID-users: The first step in management is to stop the NSAID use if possible, and determine if the symptoms improve.12 If symptoms persist after NSAID use is discontinued, the patient should be managed as others with undifferentiated dyspepsia.
Non–NSAID-related duodenal and gastric ulcers
Helicobacter pylori is now well recognized as a major risk factor for the development of peptic ulcer disease. Although most H pylori–infected patients do not develop an ulcer, as many as 95% of patients with duodenal ulcers and 80% of those with gastric ulcers are infected. These rates may be lower in the United States because of greater use of NSAIDs and a lower rate of H pylori infection than in other parts of the world.13 Successful eradication of the organism following treatment heals ulcers and reduces the risk of recurrence from 67% to 6% for patients with duodenal ulcers, and from 59% to 4% for patients with gastric ulcers.14 A meta-analysis of North American randomized controlled trials of H pylori eradication for duodenal ulcer found that one ulcer recurrence (by endoscopy) would be prevented for every 2.8 patients successfully treated.15