Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Helicobacter pylori eradication did not change ulcer recurrence or dyspepsia rates in patients who used NSAIDs

ACP J Club. 1999 Mar-April;130:38. doi:10.7326/ACPJC-1999-130-2-038


Source Citation

Hawkey CJ, Tulassay Z, Szczepanski L, et al. Randomised controlled trial of Helicobacter pylori eradication in patients on non-steroidal anti-inflammatory drugs: HELP NSAIDs study. Lancet. 1998 Sep 26;352:1016-21.


Abstract

Question

In patients who use nonsteroidal anti-inflammatory drugs (NSAIDs), can Helicobacter pylori eradication decrease dyspepsia without affecting the ulcer recurrence rate?

Design

Randomized controlled trial with 6-month follow-up.

Setting

Primary and secondary care centers in Hungary, Poland, South Africa, Spain, and the United Kingdom.

Patients

285 patients who were 18 to 85 years of age; required NSAID treatment; had H. pylori infection of the gastric mucosa; and had peptic ulcers at baseline or in the previous 5 years or had moderate or severe NSAID-associated dyspepsia. Exclusion criteria were previous H. pylori eradication treatment; treatment in the previous month with antibiotics, bismuth compounds, or steroids; use of drugs that might interact with study drugs; erosive gastroesophageal reflux disease; pyloric stenosis; or substantial bleeding in the upper gastrointestinal tract. 279 patients (mean age 55 y, 70% women) were analyzed.

Intervention

Patients were allocated to H. pylori eradication treatment twice/d with omeprazole, 20 mg; amoxicillin, 1000 mg; and clarithromycin, 500 mg (n = 142); or to control treatment twice/d with omeprazole, 20 mg, and placebo antibiotics (n = 143) for 1 week. All patients subsequently received omeprazole, 20 mg/d, until endoscopy at week 4. Patients who still had ulcers or moderate dyspepsia received omeprazole, 40 mg/d, for 4 more weeks.

Main outcome measure

Treatment failure (recurrence of ulcers, dyspepsia, or both).

Main results

Analysis was by intention to treat. No difference existed between groups in the number of patients who had treatment failure during follow-up { P = 0.6}* (Table). Fewer patients in the eradication group than in the control group were free of ulcers at 8 weeks (89% vs 100%, { P = 0.03}*). The cumulative remission rates for ulcers and for dyspepsia by the end of the study were 80% and 70%, respectively, in the eradication group and 78% and 68%, respectively, in the control group.

Conclusion

In patients who used nonsteroidal anti-inflammatory drugs, Helicobacterpylori eradication did not influence the rates of ulcer recurrence or dyspepsia over 6 months.

Source of funding: Not stated.

For correspondence: Professor C.J. Hawkey, Division of Gastroenterology, University Hospital, Nottingham NG7 2UH, England, UK. FAX 44-115-924-9924.

* P values calculated from data in article.


Table. Helicobacter pylori eradication vs control in patients who use NSAIDs†

Outcome by 6 mo Eradication Control RRR (95% CI) NNT (CI)
Recurrent ulcer or dyspepsia 38% 41% 8% (-22 to 32) Not significant

†NSAIDs = nonsteroidal anti-inflammatory drugs. Other abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.


Commentary

H. pylori and NSAIDs are the main culprits of peptic ulcer disease. Ulcers caused by H. pylori are potentially curable using cost-effective eradication regimens; ulcers caused by NSAIDs are preventable but at a price. Determining how to heal and maintain remission of an ulcer in a patient who receives NSAIDs and is infected with H. pylori has been a priority for years. The study by Hawkey and colleagues sheds welcome light on this subject. Omeprazole, amoxicillin, and clarithromycin were used to eradicate H. pylori, followed by omeprazole or placebo to heal ulcers. Successful eradication was achieved in 66% of patients, ranging from 59% in Hungary to 78% in South Africa.

The eradication regimen impaired the healing of NSAID ulcers and under such circumstances was not beneficial. This finding generates a mixture of responses. Although patients might be disappointed, researchers will be examining the explanation. Both NSAIDs and H. pylori can induce several damaging mediators and mechanisms, such as proinflammatory eicosanoids, platelet-activating factor, tumor-necrosis factor, and interference with the mucus layer and microcirculation. No evidence exists to show that these become insignificant or protective when NSAIDs and H. pylori coexist. On the other hand, omeprazole is known to lose much of its efficacy after the eradication of H. pylori. Its acid inhibitory effect diminishes, and this might explain the delayed ulcer healing in patients initially treated with omeprazole for H. pylori infection. Also, different results were obtained with another regimen that consisted of bismuth, metronidazole, and tetracycline. This regimen successfully eradicated H. pylori in 89% of patients and prevented more ulcers (1). Considering the current evidence, it could still be argued that eradicating H. pylori is worth considering before ulcers form in patients who are about to start receiving NSAIDs.

Ali S. Taha, MD, PhD
Crosshouse HospitalKilmarnock, Scotland, UK


Reference

1. Chan FK, Sung JJ, Chung SC, et al. Randomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers. Lancet. 1997;350:975-9.