In older patients receiving aspirin, H pylori eradication reduced hospitalization or death due to peptic ulcer bleeding at 2.5 y

A randomized controlled trial at 1,208 primary care centers in the U.K. found that in older patients receiving aspirin, Helicobacter pylori eradication reduced hospitalization or death due to peptic ulcer bleeding for the first 2.5 years after treatment but not in the subsequent 2.5 years. The trial included 5,352 adults age 60 years and older who were receiving aspirin (≤325 mg/d), had four or more prescriptions for 28 days of aspirin in the past year, and had a positive result on an H. pylori C13 urea breath test. About half the participants received either H. pylori eradication with a combination of oral clarithromycin (500 mg), metronidazole (400 mg), and lansoprazole (30 mg) or oral placebos twice daily for one week.

The study was published Nov. 5, 2022, by The Lancet. The following commentary by Abhilash Perisetti, MD, and Prateek Sharma, MD, was published in the ACP Journal Club section of the April Annals of Internal Medicine.

Hawkey and colleagues conducted a double-blind, randomized, controlled trial to assess the effect of H pylori eradication vs. placebo on aspirin-associated gastrointestinal ulcer bleeding in older patients with concomitant aspirin use. At 2.5 years, 6 episodes of peptic ulcer disease occurred in the eradication group vs. 17 episodes in the placebo group. The study results, statistical methods, and discussion are well reported, but several issues need consideration.

First, only patients aged ≥60 years who were not using proton-pump inhibitors or NSAIDs were included; polypharmacy with these drugs is common in this age group given likely cardiovascular and gastrointestinal risk factors. Excluding these patients means that the trial included only healthier older adults and restricts the findings to this select group. Second, in the USA, an aspirin dose of 81 mg/d is considered to be low-dose and 325 mg/d is high-dose. Hawkey and colleagues included patients receiving up to 325 mg/d. This is important because H pylori eradication might be more beneficial in patients receiving high- vs. low-dose aspirin. From this trial and context, it is difficult to draw conclusions about which patients would benefit most from H pylori eradication. Third, eradication involved a triple-drug regimen that included a macrolide (clarithromycin) for 7 days. Major North American gastroenterology societies recommend treatment for 10 to 14 days and special attention for macrolide resistance. This restricts the applicability of the findings in the U.S. population, where antibiotic resistance and dosing duration differ from those in the UK. Fourth, the number of primary outcome events was too low for meaningful interpretation. The estimated numbers needed to treat of 243 for both the primary outcome and ulcer bleeding are too high to justify implementing primary prophylaxis of H pylori eradication without testing in primary care.

These limitations may affect the extent to which these results will change current practice of H pylori eradication in patients receiving aspirin, especially older patients.