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Therapeutics

Omeprazole was better than H. pylori eradication for preventing recurrent GI bleeding in patients receiving naproxen

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ACP J Club. 2001 Nov-Dec;135:92. doi:10.7326/ACPJC-2001-135-3-092


Source Citation

Chan FK, Chung S, Suen BY, et al. Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen. N Engl J Med. 2001 Mar 29;344:967-73. [PubMed ID: 11274623]


Abstract

Question

In patients with upper gastrointestinal (GI) bleeding and Helicobacter pylori infection who are taking low-dose aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), is eradication of H. pylori equivalent to maintenance therapy with omeprazole for preventing recurrent upper GI bleeding?

Design

Randomized (allocation concealed*), blinded (outcome assessors),* controlled trial with median follow-up of 6 months.

Setting

Prince of Wales Hospital, Hong Kong.

Patients

400 patients (mean age 68 y, 62% men) with a history of confirmed upper GI bleeding (ulcers or erosions) who had H. pylori infection with an ongoing need for aspirin (≤325 mg/d) (n = 250) or other NSAIDs (n = 150). Exclusion criteria included use of nonaspirin NSAIDs plus low-dose aspirin, corticosteroids, or anticoagulants and previous gastric surgery. 95% of patients completed the study.

Intervention

After having ulcers healed while receiving omeprazole, 20 mg/d for ≥ 8 weeks, those patients previously taking aspirin were given aspirin, 80 mg/d, and those previously taking other NSAIDs were given naproxen, 500 mg twice daily, for 6 months. All patients were also separately assigned to omeprazole, 20 mg/d for 6 months, or to eradication therapy for 1 week (bismuth subcitrate, 120 mg; tetracycline, 500 mg; and metronidazole, 400 mg, all 4 times/d) followed by placebo for 6 months. 125 patients in the aspirin group and 75 in the other NSAIDs group were allocated to omeprazole, and 125 patients in the aspirin group and 75 in the other NSAIDs group were allocated to H. pylori eradication.

Main outcome measure

Recurrent upper GI bleeding.

Main results

Among patients taking NSAIDs, those in the omeprazole group had a lower rate of recurrent upper GI bleeding (P = 0.005) (Table). Among patients taking aspirin, the groups did not differ for recurrent upper GI bleeding (Table).

Conclusions

In patients with a history of upper gastrointestinal bleeding and Helicobacter pylori infection who were taking low-dose aspirin, H. pylori eradication was comparable to omeprazole in preventing recurrent bleeding. In contrast, omeprazole was superior to H. pylori eradication in preventing recurrent bleeding in patients who were taking other NSAIDs.

*See Glossary.

Sources of funding: Research Grant Council and Health Services Research Committee of Hong Kong.

For correspondence: Dr. F.K. Chan, Department of Medicine and Therapeutics, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong, China. FAX 852-2637-3852.


Table. Omeprazole vs eradication of H. pylori in recurrent upper gastrointestinal bleeding at 6 months in patients receiving aspirin or naproxen†

Group Omeprazole Eradication RRR (95% CI) NNT (CI)
Aspirin 0.9% 1.9% 52% (−145 to 250) Not significant
Naproxen 4.4% 18.8% 77% (35 to 118) 7 (5 to 23)

†Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.


Commentary

H. pylori infection and NSAID use are independent risk factors for ulcer disease, but whether H. pylori infection potentiates the development of NSAID-induced ulcers is controversial. Most trials find that H. pylori does not significantly increase the risk for ulcers in NSAID users (1). However, NSAID-naive patients who were given H. pylori therapy before beginning an 8-week course of naproxen developed ulcers less often than patients not given H. pylori therapy (2). In contrast, a larger double-blind trial subsequently found that H. pylori therapy decreased healing of gastric ulcers and had no effect on ulcer recurrence at 6 months in NSAID users (3).

The current study by Chan and colleagues used complicated ulcers, one of the most clinically important adverse effects of NSAIDs, as an inclusion criterion and end point. Rebleeding remained unacceptably high after H. pylori therapy in NSAID users (19% at 6 mo). The lack of a placebo group, although ethically understandable, prevents us from determining whether H. pylori therapy may provide some benefit. In contrast, recurrent bleeding was uncommon among low-dose aspirin users after H. pylori therapy. Again, the relative benefit of H. pylori therapy compared with no therapy is uncertain because of the lack of a placebo group.

How should these data be applied in clinical practice? NSAID or aspirin users without past or present ulcer disease need not be tested for H. pylori. In individual patients with an ulcer, one cannot be certain whether H. pylori or NSAIDs or aspirin is responsible, and each risk should be removed. If low-dose aspirin must be continued, I would add a proton-pump inhibitor, even after H. pylori therapy. If NSAIDs must be continued, I would switch to a specific cyclooxygenase 2 inhibitor or add cotherapy, or both.

Loren Laine, MD
University of Southern California School of Medicine
Los Angeles, California, USA


References

1. Laine L. Approaches to nonsteroidal anti-inflammatory drug use in the high-risk patient. Gastroenterology. 2001;120:594-606.

2. 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.

3. 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;352:1016-21.