Authors' objectives: Peptic ulcers in patients on aspirin are associated with Helicobacter pylori infection. We investigated whether H. pylori eradication would protect against aspirin-associated ulcer bleeding. Low-dose aspirin is valuable in protecting people at increased risk from having heart attacks and strokes, but increases the risk of bleeding, particularly from stomach ulcers. The main cause of stomach ulcers is the bacteria Helicobacter pylori. We carried out a trial to test whether antibiotic treatment to eradicate Helicobacter pylori would protect participants from ulcer bleeding.

Authors' results and conclusions: Helicobacter pylori eradication protects against ulcer bleeding in people on aspirin, but this may not be sustained. Between 14 September 2012 and 22 November 2017, 30,166 participants underwent breath testing, of whom 5367 had a positive result and 5352 were randomised to an ITT population of 2677 (eradication treatment) and 2675 (placebo). Baseline characteristics Median age at consent was 73.6 (standard deviation 6.9) years, and 72.8% of the participants were male. Coronary heart disease was the most common comorbidity among aspirin indications (49.2%), and 10.0% were taking nitrates. More than half the participants (52.8%) were ex-smokers, but a history of peptic ulcer was uncommon (1.8%).

Authors' methods: The Helicobacter Eradication Aspirin Trial was a randomised placebo-controlled trial (European Union Drug Regulating Authorities Clinical Trials 2011-003425-96), conducted in United Kingdom primary care using routinely collected clinical data. Consenting participants aged ≥ 60 years prescribed aspirin ≤ 325 mg but not ulcerogenic or gastroprotective medication underwent C13 urea breath testing for H. pylori. Those with a positive test were randomised to receive either a combination of clarithromycin 500 mg, metronidazole 400 mg and lansoprazole 30 mg, or placebos twice daily for 7 days. The primary outcome, time to death or hospitalisation due to peptic ulcer bleeding, was analysed using a Cox proportional hazards model. Studying subjects already established on aspirin probably contributed to the low event rate. A future study should investigate subjects starting on aspirin when the event rate is higher. General practitioners in 1208 United Kingdom general practices searched their records to find people aged 60 and over who were taking low-dose aspirin. We used a breath test to detect H. pylori infection. Those with a positive result were randomly assigned to receive well-established eradication treatment with two antibiotics (clarithromycin and metronidazole) and a drug that reduces stomach acidity (lansoprazole), or matching placebos (dummy pills) twice daily for a week. We used routinely collected general practitioner and hospital data and death certificates to see if the treatment reduced the outcome of hospitalisation or death from ulcer bleeding. The Helicobacter Eradication Aspirin Trial (HEAT) was a randomised placebo-controlled trial conducted in UK primary care which used routinely collected clinical data to identify possible participants and to follow clinical progress. It was conducted in 1208 UK primary care practices, of which 1055 enrolled at least one participant. Recruitment Consenting participants aged ≥ 60 years who were prescribed aspirin (≤ 325 mg) but not ulcerative or gastroprotective medication made a single baseline trial visit for collection of clinical data and underwent a C13 urea breath test for H. pylori. Those with a positive test were randomised to receive either a combination of clarithromycin 500 mg, metronidazole 400 mg and lansoprazole 30 mg or placebo twice daily for 7 days. Participants were asked to record the timing of each dose and record all possible side effects. Those recording taking at least eight doses formed the per-protocol population.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/09/55/52

Year Published: 2025

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/LLKF7871

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

DOI: 10.3310/LLKF7871

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk