Letter to the Editor: Helicobacter pylori eradication in aspirin users - gastroprotection established, cardiovascular implications to be clarified

Abstract

Semeya et al recently published a study in the World Journal of Gastroenterology reported that Helicobacter pylori eradication in chronic low-dose aspirin users was associated with a marked reduction in peptic ulcer bleeding and with less cardiovascular disease progression. The gastrointestinal benefit appears clinically important and is consistent with previous evidence supporting testing and eradication strategies in selected high-risk aspirin users. However, the cardiovascular findings should be interpreted with caution because the composite outcome did not consist exclusively of hard atherosclerotic endpoints, the follow-up period was relatively short, and residual confounding cannot be fully excluded. In addition, the modest eradication rate with levofloxacin-based therapy and the heterogeneity of concomitant antithrombotic treatment may have influenced the observed associations. Further prospective studies with longer follow-up and hard cardiovascular outcomes are needed to clarify whether eradication provides true cardiovascular benefit beyond gastrointestinal protection.

Key Words: Helicobacter pylori; Aspirin; Peptic ulcer bleeding; Cardiovascular risk; Eradication therapy; Gastroprotection

Core Tip: Helicobacter pylori eradication in chronic aspirin users appears to provide meaningful gastrointestinal protection and may reduce peptic ulcer bleeding risk. However, the reported cardiovascular benefit should be interpreted cautiously because of short follow-up, composite endpoint selection, possible residual confounding, and modest eradication success. Future studies should focus on optimized eradication strategies and hard cardiovascular outcomes.

TO THE EDITOR

I read with interest the recent study by Semeya et al[1] published on the World Journal of Gastroenterology evaluating the impact of Helicobacter pylori (H. pylori) eradication on peptic ulcer bleeding and cardiovascular disease progression in chronic low-dose aspirin users. H. pylori remains a major global health concern with well-established gastrointestinal and systemic implications[2]. The authors address an important clinical interface between gastroprotection and cardiovascular risk management in a patient population frequently encountered in daily practice.

The association between persistent H. pylori infection and increased ulcer bleeding risk in aspirin users is biologically plausible and consistent with prior evidence. The combined effect of aspirin-induced cyclooxygenase-1 inhibition and H. pylori-mediated mucosal inflammation has been well described[3]. In this context, the magnitude of peptic ulcer bleeding reduction observed in the present cohort, corresponding to a 69% relative risk reduction, provides meaningful real-world support for the gastroprotective value of H. pylori eradication and is in line with randomized evidence such as the HEAT trial[4]. These findings support targeted testing and eradication strategies in selected high-risk aspirin users and are consistent with contemporary recommendations for patients at increased bleeding risk.

The cardiovascular findings, however, deserve cautious interpretation. In this study, cardiovascular progression was defined as a composite of new revascularization, hospitalization for unstable angina, or worsening Canadian Cardiovascular Society angina class. Although these outcomes are clinically relevant, they differ from hard atherosclerotic endpoints such as myocardial infarction, stroke, or cardiovascular mortality. In addition, a follow-up period of only six months may be too short to assess meaningful modification of atherosclerotic burden. Changes in angina classification or revascularization rates over this interval may partly reflect clinical decision-making and referral patterns rather than true vascular regression.

Chronic H. pylori infection has been linked to systemic inflammatory activation, endothelial dysfunction, and disturbances in lipid metabolism[5-7]. Although observational evidence suggests a possible vascular association, causality remains uncertain. In the present cohort, baseline ischemic heart disease was more common in H. pylori-positive individuals, which raises the possibility that infection status may reflect broader cardiometabolic vulnerability rather than an independent short-term driver of cardiovascular progression. Despite multivariable adjustment and E-value analysis, residual confounding cannot be excluded.

Another issue is the eradication rate of 51.9% with levofloxacin-based triple therapy. In settings where fluoroquinolone resistance is increasing, such a result is not unexpected[8]. Current consensus recommendations favor resistance-adapted or bismuth-containing regimens to improve eradication success[9]. This relatively modest eradication rate represents an important limitation and may have influenced the reported associations. It also underlines the need for optimized, and ideally susceptibility-guided, eradication strategies.

It is also noteworthy that all participants were receiving aspirin together with additional antithrombotic or anticoagulant agents. Although this reflects real-world secondary prevention practice, such treatment heterogeneity introduces variability in both bleeding risk and cardiovascular risk. Statistical adjustment is helpful, but complex pharmacodynamic interactions may not be fully accounted for in observational analyses.

Treatment adherence also deserves attention, particularly in older patients receiving multiple medications. Complex regimens, adverse effects, and insufficient follow-up may all contribute to incomplete eradication in routine practice. Practical measures such as patient education, simplified regimens, and structured follow-up may improve adherence and thereby increase eradication success.

Overall, the gastroprotective benefit of H. pylori eradication in chronic aspirin users appears well supported, clinically relevant, and aligned with current guidance. Whether eradication also confers meaningful cardiovascular protection remains uncertain and should be regarded as hypothesis-generating at present. Longer-term prospective studies incorporating hard cardiovascular endpoints, including myocardial infarction, stroke, and cardiovascular mortality, are needed to determine whether the observed association reflects true biological benefit or residual confounding. In addition, the limitations related to eradication success and treatment adherence highlight the need for strategies that are both evidence-based and feasible in routine clinical practice.

Semeya et al[1] have provided valuable data that stimulate discussion at the intersection of gastroenterology and cardiovascular medicine. Clarifying the broader systemic implications of H. pylori management in aspirin-treated populations remains an important area for future research. Further clarification regarding cardiovascular endpoint selection and eradication efficacy may help refine the clinical interpretation of this important study.