Treatment of Peptic Ulcer Disease and Nonulcer Dyspepsia

Journal of Family Practice, July, 2001 by Linda N. Meurer

KEY POINTS

* The test and treat strategy for primary care patients presenting with nonreflux type dyspepsia is cost-effective.

* Choice of Helicobacter pylori eradication therapy depends on compliance and cost; a preferred initial approach is a combination including a proton pump inhibitor (PPI), amoxicillin, and clarithromycin dosed twice daily for up to 14 days.

* If discontinuing nonsteroidal anti-inflammatory drugs is not possible, treating concurrently with a doubled dose of [H.sub.2]-receptor agonists, a PPI, or misoprostol are options that decrease symptoms and can prevent ulcers.

* Treatment of nonulcer dyspepsia is difficult; the best options include acid suppression and antidepressants.

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. (J Fam Pract 2001; 50:614-619)

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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 strategy[3,4] 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 (Table 1) 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]

TABLE 1
ALARM SIGNS SUGGESTING COMPLICATED ULCER
OR INCREASED RISK FOR CANCER

Older than 45 years(*)

Family history of gastric cancer

Previous peptic ulcer

Significant weight loss (eg. [is greater than] 10% of body weight)

Rectal bleeding or melena

Anemia

Abdominal mass

Hematemesis

Early satiety

(*) A cutoff of age 50 years has been recommended in Canada.

NOTE: Recommendations adapted from the American Gastroenterological
Association's position statement on Helicobacter pylori.

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 [H.sub.2]-receptor agonists ([H.sub.2]RAs) are ineffective at preventing NSAID-related gastric ulcers, but double doses of [H.sub.2]RAs (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 [is less than] .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 [is less than] .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.