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Am Fam Physician. 2019;99(12):783-784

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Clinical Question

Should clinicians perform laboratory screening for and eradicate Helicobacter pylori in patients before initiating long-term therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) to reduce the risk of peptic ulcer disease?

Evidence-Based Answer

Physicians should perform laboratory screening for and eradicate H. pylori before initiating long-term NSAID therapy in NSAID-naive patients to reduce the risk of peptic ulcer disease. (Strength of Recommendation [SOR]: A, based on meta-analyses of randomized controlled trials [RCTs].) Physicians should screen for and eradicate H. pylori before initiating long-term NSAID therapy in patients with a history of peptic ulcers. (SOR: B, based on a meta-analysis of case-controlled studies.)

Evidence Summary

A 2012 meta-analysis of seven RCTs (N = 1,254) examined whether eradication therapy for H. pylori infection decreased the incidence of peptic ulcer disease in adults receiving long-term NSAID therapy.1 Western and Asian populations were represented. The primary end point was the development of peptic ulcer disease during follow-up. Most participants were female (61% to 81%). Peptic ulcer disease developed in 6.4% of participants who underwent eradication therapy compared with 11.8% of those who did not (odds ratio [OR] = 0.50; 95% CI, 0.36 to 0.74; number needed to treat [NNT] = 18). In a subanalysis of three studies of NSAID-naive patients (n = 532), a significant risk reduction was noted in the eradication group: 10 of 262 participants (3.8%) in the eradication group developed a peptic ulcer vs. 37 of 270 (13.7%) in the noneradication group (OR = 0.26; 95% CI, 0.14 to 0.49; NNT = 10). In a subanalysis of participants receiving long-term NSAID therapy (n = 822), there was no statistical difference between the eradication and noneradication groups (OR = 0.74; 95% CI, 0.46 to 1.20).

A 2002 meta-analysis of 16 case-control or cross-sectional studies of adults (N = 1,625) linked H. pylori infection to development of peptic ulcer disease. NSAID users with ulcers were more likely to have H. pylori infection (OR = 2.12; 95% CI, 1.68 to 2.67). In a subanalysis of five controlled trials, H. pylori infection conferred additional risk beyond NSAID use alone (OR = 3.53; 95% CI, 2.16 to 5.75). A subanalysis of six case-control studies revealed that the risk of ulcer bleeding was greater when both NSAID use and H. pylori infection were present (OR = 6.13; 95% CI, 3.93 to 9.45).2 Long-term NSAID use was defined in most studies as at least four weeks.

Recommendations from Others

The American College of Gastroenterology (ACG) recognizes H. pylori infection as a significant modifiable risk factor for NSAID-induced ulcers and ulcer complications (e.g., bleeding). The ACG recommends testing for H. pylori infection before initiating long-term NSAID therapy and offering eradication therapy to those with positive results. The ACG recommends testing all patients who have active peptic ulcer disease or a history of peptic ulcers and no documentation of cure.3 The Japanese Society of Gastroenterology recommends eradication of H. pylori for prevention of ulcers in NSAID-naive patients who are beginning treatment with NSAIDs, but not in those already being treated with NSAIDs.4 The Maastricht V/Florence Consensus Report, which included input from 43 experts from 24 countries, recommends testing for H. pylori in patients with a history of peptic ulcers who are receiving aspirin and other NSAIDs.5

Copyright © Family Physicians Inquiries Network. Used with permission.

Clinical Inquiries provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review. The strength of recommendations and the level of evidence for individual studies are rated using criteria developed by the Evidence-Based Medicine Working Group (

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