Study title: Helicobacter pylori Screening to Prevent Gastrointestinal Bleeding in Patients with Acute Myocardial Infarction (HELP-MI SWEDEHEART) – Design and Rationale of a Cluster Randomized, Crossover, Registry-Based Clinical Trial

Presented at: ESC Congress 2025

Link: https://esc365.escardio.org/presentation/312233

Prepared by: Dr. Okan Oğuzhan Ovaz, Dr. Mustafa Yenerçağ

Introduction
The use of antithrombotic agents has significantly reduced the incidence of recurrent ischemic events in patients with acute myocardial infarction (MI). However, it has been associated with a marked increase in the risk of upper gastrointestinal bleeding (UGIB). Chronic gastric infection with Helicobacter pylori (H. pylori) may represent an overlooked and modifiable risk factor for UGIB following MI.

Objective
To evaluate whether routine screening for H. pylori infection and subsequent eradication in patients hospitalized for acute myocardial infarction can reduce bleeding events and improve clinical outcomes.

Methods
This is a nationwide, open-label, two-period, two-sequence, cluster-randomized, crossover clinical trial. Thirty-five Swedish hospitals were divided into 18 clusters, and each cluster was randomly assigned either to routine H. pylori screening for all patients with acute myocardial infarction for one year, followed by usual care after a 2-month washout period, or vice versa. A total of 18,466 patients were enrolled, with 9,245 patients in the screening periods and 9,221 patients in the non-screening periods. During the screening periods, all patients hospitalized for myocardial infarction underwent routine H. pylori screening using the urea breath test in addition to standard care. Upper gastrointestinal bleeding was analyzed in the intention-to-treat population using a negative binomial model. The primary endpoint of the study is upper gastrointestinal bleeding. Secondary endpoints include all-cause mortality, cardiovascular mortality, rehospitalization due to myocardial infarction, rehospitalization due to stroke or heart failure, and upper gastrointestinal bleeding requiring blood transfusion.

Results
At admission, 2,284 patients during the screening periods and 2,275 patients during the non-screening periods (both 24.7%) were using proton pump inhibitors. During the screening periods, 6,480 patients (70%) underwent testing, of whom 1,532 (23.6%) were found to be H. pylori positive. After a median follow-up of 1.9 years, the primary endpoint of upper gastrointestinal bleeding occurred in 299 patients in the screening group (incidence rate: 16.8 per 1,000 person-years; 3-year cumulative risk: 4.1%) and in 336 patients in the usual care group (incidence rate: 19.2 per 1,000 person-years; 3-year cumulative risk: 4.6%) (rate ratio [RR]: 0.90; 95% CI: 0.77–1.05; p = 0.18).
In predefined, unadjusted subgroup analyses for multiplicity, the intervention effect was heterogeneous:

• Patients without anemia: RR 0.98 (95% CI: 0.80–1.21)
• Patients with mild anemia: RR 0.64 (95% CI: 0.42–0.98)
• Patients with moderate-to-severe anemia: RR 0.44 (95% CI: 0.23–0.87)
  (Interaction p = 0.03)

Conclusions
The effect of the primary endpoint varied according to the presence of anemia. In patients with acute myocardial infarction and mild or moderate-to-severe anemia, H. pylori screening was associated with a lower risk of upper gastrointestinal bleeding. No significant differences were observed between the screening and control groups with respect to secondary endpoints, including all-cause mortality, myocardial infarction, and major cardiovascular or cerebrovascular events.

Discussion
Routine H. pylori screening did not significantly reduce the risk of upper gastrointestinal bleeding in an unselected population of patients with acute myocardial infarction. However, in populations with a higher prevalence of infection and in subgroups with concomitant anemia—who are at higher bleeding risk—the potential clinical benefit of H. pylori screening should not be overlooked.