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Interaction of Helicobacter pylori infection and low-dose aspirin in the upper gastrointestinal tract: Implications for clinical practice

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Low-dose aspirin has been shown to increase the risk of upper gastrointestinal tract injury. Risk factors in upper gastrointestinal complications in low-dose aspirin users are less well defined than in other NSAID users, and there are enough intrinsic differences in the two agents to discuss them separately. In particularly, the role of Helicobacter pylori and the benefit of its eradication in decreasing the risk of upper gastrointestinal tract injury in low-dose ASA users remains controversial. Various consensus groups have recommended H. pylori testing and eradication in low-dose ASA users with a prior history of peptic ulcer or ulcer bleeding. The basis of this recommendation is derived from a limited, albeit expanding evidence on the role of H. pylori in upper gastrointestinal tract injury in low-dose ASA users and on the effectiveness of H. pylori eradication in reducing the risk of complications such as rebleeding in high-risk patients.

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Clinical scenario

A general health practitioner calls you concerning a 72-year-old male patient on low-dose aspirin for known ischaemic heart disease. Past medical history reveals a peptic ulcer bleed 1 year ago. Helicobacter pylori status is unknown. Before testing for H. pylori, your colleague wishes to know if H. pylori increases the risk of low-dose aspirin related gastrointestinal injury and whether eradicating it would be beneficial.

Pathophysiology of upper GI injury

Low-dose ASA and H. pylori damage the gastric mucosa by mechanisms that may be distinct or shared. The mechanism of low-dose ASA induced upper GI injury is incompletely understood, however, low-dose ASA likely exerts both systemic and topical effects that may interact with H. pylori in a synergistic or antagonistic manner [1], [2], [3], [4], [5], [6], [7], [8] (Table 1).

H. pylori positive low-dose ASA users: clinical studies

Literature is sparse and controversial concerning the interaction of H. pylori and low-dose ASA in causing upper GI injury. A recent systematic review including 13 studies by Fletcher et al [18] concluded that the current available evidence was insufficient to perform a meta-analysis and that no firm conclusion could be drawn regarding the impact of H. pylori on upper GI bleeding risk in ASA users. Indeed ten of 13 studies examined were cohort studies that comprised a heterogeneous group with

Data from NSAID studies

Two meta-analyses lend indirect support to the role of H. pylori in upper GI complications in low-dose ASA users. In a meta-analysis by Huang et al [25] including 16 studies that collectively enrolled 1652 NSAID users, peptic ulcer disease was significantly more common in patients positive than in those negative for H. pylori. The presence of both H. pylori and NSAIDs increased the risk of ulcer bleeding 6.13-fold whereas H. pylori alone and NSAIDs increased the risk of ulcer bleeding 1.79-fold

Concomitant use of NSAIDs, anti-coagulants and other anti-platelet drugs

Several studies have shown that the risk of ulcer rebleeding is significantly increased in patients on low-dose ASA and concomitant use of NSAIDs, anticoagulants or other anti-platelet drugs [1], [2], [3]. There are no studies specifically examining the risk reducing benefit of H. pylori eradication in these patients either for primary or secondary prophylaxis.

It would be reasonable to suggest H. pylori eradication in low-dose ASA users on concomitant NSAIDS if there are indications for

Cost-effectiveness of test and treating H. pylori

There are currently no studies specifically addressing the cost-effectiveness of test and treating H. pylori in low-dose ASA users. However, in a decision analysis model of test and treating H. pylori for patients requiring chronic NSAID therapy [30], this strategy could reduce NSAID-related adverse events for average risk patients at an acceptable incremental cost. The clinical and cost-effectiveness benefit was also shown to increase with increasing ulcer risk. Another UK report [31] showed

Recommendations by consensus groups

A certain degree of misinformation may surround the risk and benefit of gastroprotective strategies in NSAID and low-dose ASA users [32]. In an aim to standardize our approach to this matter, various consensus groups have developed recommendations concerning the management of H. pylori [33], [34], [35] and concerning GI risk reduction in NSAID and antiplatelet users [36], [37].

It is acknowledge that the interaction between H. pylori infection and NSAIDs including low-dose ASA in peptic ulcer

Summary

In the clinical scenario presented, the patient has several risk factors for recurrent peptic ulcer bleeding, namely a previous history of ulcer bleed, advanced age, and on-going use of low-dose ASA. In line with current evidence and international guidelines, we would suggest testing and treating the patient for H. pylori. It would also be reasonable to consider a long-term gastroprotective agent in view of his multiple risk factors (Table 3).

It is important to acknowledge that a substantial

Conflicts of interest

None declared.

References (37)

  • T. Brzozowski et al.

    Interaction of nonsteroidal anti-inflammatory drugs (NSAID) with Helicobacter pylori in the stomach of humans and experimental animals

    J Physiol Pharmacol

    (2006)
  • F.K. Chan 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)
  • K. Iijima et al.

    Gastric acid secretion level modulates the association between Helicobacter pylori infection and low-dose aspirin-induced gastropathy

    J Gastroenterol

    (2011)
  • C.J. Hawkey et al.

    Influence of sex and Helicobacter pylori on development and healing of gastroduodenal lesions in non-steroidal anti-inflammatory drug users

    Gut

    (2002)
  • J. Hart et al.

    Predictors of gastroduodenal erosions in patients taking low-dose aspirin

    Aliment Pharmacol Ther

    (2010 Jan)
  • T. Hagiwara et al.

    Long-term proton pump inhibitor administration worsens atrophic corpus gastritis and promotes adenocarcinoma development in Mongolian gerbils infected with Helicobacter pylori

    Gut

    (2011)
  • F.K. Chan et al.

    Does eradication of Helicobacter pylori impair healing of nonsteroidal anti-inflammatory drug associated bleeding peptic ulcers? A prospective randomized study

    Aliment Pharmacol Ther

    (1998)
  • R. Pajdo et al.

    Effect of Helicobacter pylori infection on the phenomenon of gastric mucosal adaptation to repetitive aspirin insult in mongolian gerbils. Role of reactive oxygen metabolites and proinflammatory cytokines (abstr)

    Gastroenterology

    (2010)

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