ArticlesRandomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers
Introduction
Peptic ulcer disease caused by non-steroidal anti-inflammatory drug (NSAID) therapy is a health-care issue worldwide. In the UK, about 1·5 million people aged over 60 years take NSAIDs at any one time.1 Patients who take NSAIDs have a four-fold to six-fold increased risk of developing peptic ulcers.2, 3 Every year, about 12 000 ulcer complications occur in the UK as a result of NSAID therapy.4 Although chronic NSAID users are at increased risk of ulcer disease, those who take intermittent short-course NSAID therapy are also at risk of the disease. Most ulcer complications tend to develop in the first few weeks of therapy, particularly among individuals without previous exposure to NSAIDs.3, 5 The risk of ulcer complications is greatest among the elderly and patients with comorbid disease.2, 3 Up to 60% of ulcer complications occur without antecedent symptoms.6 The annual direct medical costs associated with these complications is about $3·9 billion in the USA.7
Previous studies have shown that prophylactic therapy with misoprostol, famotidine, and omeprazole is effective in the prevention of NSAID-induced ulcers.8, 9, 10 However, these prophylactic regimens are very expensive.11 Cost-effective measures to prevent NSAID-induced ulcer disease are not available.
H pylori is present in about 50% of patients with NSAID-associated ulcer disease.12, 13 Studies of the interaction between H pylori infection and NSAIDs have reported conflicting findings.12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26 Whether H pylori infection increases the risk of ulcer development in users of NSAIDs is not known.
The aim of our study was to investigate whether eradication of H pylori before the start of NSAID therapy reduced the occurrence of gastroduodenal ulcers in patients without previous exposure to NSAIDs. We postulated that underlying infection with H pylori increases the predisposition of NSAID users to develop ulcers. Thus, eradication of H pylori could protect these patients from developing peptic ulcers.
Section snippets
Methods
Patients with musculoskeletal disorders that required NSAID therapy were eligible for the study. We recruited patients from the medical outpatient clinic at Prince of Wales Hospital, Hong Kong, and from the family clinic of the Chinese University of Hong Kong. We excluded patients if they: were younger than 18 years; had been previously exposed to NSAIDs (including aspirin) for longer than 1 month; had taken NSAIDs (including aspirin), antiulcer drugs, steroid, anticoagulants, or cytotoxic
Results
202 consecutive patients agreed to take part and underwent endoscopy for enrolment in the trial. Of these patients, 91 were not infected by H pylori, two had ulcers at initial endoscopy, and nine patients with H pylori refused to participate in the study after endoscopy. 100 patients were randomly assigned treatment in two groups of 50. Eight withdrew after randomisation and defaulted follow-up (naproxen group: one refused to undergo second endoscopy, one refused to take part, and one patient
Discussion
The interaction between H pylori infection and use of NSAIDs in the pathogenesis of peptic ulcer is unclear. Most of the available data is from cross-sectional studies based on chronic NSAID users, with conflicting results.12, 13, 14, 15, 16, 17, 18, 19, 20 Two studies reported a higher rate of H pylori in NSAID users with gastroduodenal lesions than in those with normal mucosa.13, 20 Others found significantly more ulcers in NSAID users who were H pylori positive than in users not infected
References (28)
- et al.
Nonsteroidal anti-inflammatory drug-associated gastropathy: incidence and risk factors model
Am J Med
(1991) - et al.
Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs
Lancet
(1994) - et al.
Long-term non-steroidal antiinflammatory drug use and Helicobacter pylori infection
Gastroenterology
(1991) - et al.
Long-term non-steroidal anti-inflammatory drug use and gastroduodenal injury: the role of
Helicobacter pylori. Gastroenetrology
(1992) Anti-inflammatory drugs and the gut-ulcerative damage and protection from cancer
Excerpta Medica
(1995)Non-steroidal anti-inflammatory drug gastropathy: causes and treatment
Scand J Gastroenterol
(1996)- et al.
Risks for serious gastrointestinal complications related to the use of non-steroidal anti-inflammatory drugs: a meta-analysis
Ann Intern Med
(1991) - et al.
Non-steroidal anti-inflammatory drugs and bleeding peptic ulcer
Lancet
(1986) Direct medical costs of disease and gastrointestinal side effects during treatment of arthritis
Am J Med
(1984)- et al.
Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal antiinflammatory drugs: a randomized, double-blind, placebo-controlled trial
Am Intern Med
(1995)