29th September 2025, A/Prof Chee L Khoo
I must admit that I have been doing this for many years on an ad hoc basis. I have been screening for helicobacter pylori (HP) infection in patients who need to be on aspirin (primary or secondary prevention of coronary artery disease). This isn’t what is recommended in any cardiovascular (CV) disease guidelines until recently but the evidence is not robust. It is logical though. Obviously, once we find HP infection, we are obliged to treat to eradicate it (for other non-bleeding reasons as well). The research questions are 1) should we be screening for HP in these patients? 2) will screening and subsequent treatment help prevent gastrointestinal bleeding?
Sometimes we routinely do things based on some data and some logical associations. These are facts that we know:
Aspirin is widely recommended for the secondary prevention of thrombotic vascular disease. Its use is limited principally by increased risk of bleeding, particularly from the gastrointestinal tract (1,2). The risks of CV events are high compared with the known risks of bleeding.
The risks of upper gastrointestinal bleeding can be mitigated in part by acid suppression with proton pump inhibitors (PPI) and probably histamine H2-receptor antagonists (2-4).
The balance of benefits vs harms doesn’t quite work out with primary prevention because the risk of bleeding outweighs the benefits from future CV events. HP might play a causal role in the development of peptic ulceration and ulcer bleeding (5-7).
Since HP infection increases the risk of peptic ulcer and ulcer bleeding and so does aspirin, eradicating HP infection should reduce the risk of bleeding in patients on aspirin for secondary thrombotic vascular disease. It therefore, makes sense to screen for HP infection and treat those that test positive and it should reduce the bleeding risk, right?
Well, three years ago, the Helicobacter Eradication Aspirin Trial [HEAT] trial sought to answer some of those questions (8). They sought to see whether eradication of HP infection in patients on aspirin would protect them from aspirin related peptic bleeding. 5352 patients >60 years old who were on ≤ 325mg aspirin a day and tested positive for HP were randomised to either triple therapy (clarithromycin, metronidazole and a PPI or placebo for two weeks. The primary outcome was time to hospitalisation or death due to definite or probable peptic ulcer bleeding. In the first 2.5 years, there was a 65% reduction of incidence of the primary outcome (peptic ulcer) but that difference was lost after 2.5 years.
In a very recent clinical trial, the HELP-MI SWEDEHEART, 35 Swedish hospitals were randomised to either no screening for HP or screening all patients with acute myocardial infarction admitted into hospital. After one year, the allocated hospitals (randomised to screen or not to screen) were reallocated into the other group. Decisions on eradication treatment based on those findings were at the discretion of the caring physician.
A total of 18 466 patients with myocardial infarction were followed up: 9245 during the screening periods and 9221 during the non-screening periods. 24.7% of participants in both groups were already on a PPI. During screening periods, 6480 patients (70%) had undergone testing, of those 1532 (23.6%) tested positive for HP. Among the 1532 patients who tested positive, 1481 (96.6%) received eradication therapy. After a median follow-up of 1.9 years, there was a 10% reduction in bleeding rates in the screened group but it was not statistically significant (p=0.18). In other words, HP screening in patients with myocardial infarction on aspirin did not significantly reduce GI bleeding.
So, does that mean HP screening is really not helpful. Well, the prevalence rate of HP in the trial was 23%. In some geographical areas the prevalence might be more like 50% especially amongst cardiovascular disease populations (9). A higher positive rate on screening might mean treating more patients and that might change our conclusion. Further, the screening rate even in the intervention group was only 70%. They may have picked up more HP positive patients which may have undergone eradication therapy and reduce the number of GI bleeding.
A sub-group analysis of the HELP-MI SWEDEHEART data, in patients with anaemia, particularly those with moderate to severe anaemia, H pylori screening was associated with a lower risk of upper gastrointestinal bleeding. Further, patients with renal impairment also benefited from HP screening.
In a scoping review of HP in 8 Australian population-based studies, prevalence ranged from 38.0% in 1991 to 15.1% in 2002. However, estimated prevalence across all non-clinical population studies in diverse sub-groups (n = 29) has varied dramatically. Decreased prevalence has been more marked in populations with gastrointestinal symptoms and conditions compared to non-clinical populations. Data on HP prevalence in vulnerable populations are lacking (11).
My co-editor, Dr John Goswell, suggested that perhaps:
Routine screening might be better justified in
- Symptomatic patients (heartburn/indigestion etc)
- Those of Indian/SE Asian or north African origin
- Those who develop any GI symptoms on aspirin
In summary, while the study earlier in 2022 (HEAT) showed that HP screening (and eradication) reduced GI bleeding in patients with prescribed aspirin, the effect was not sustained after 2.5 years. The HELP-MI SWEDEHEART concluded overall the lack of benefit of HP screening in patients with myocardial infarction, the results might be different in communities with higher prevalence of HP. There is a suggestion that in patients with anaemia and renal impairment, screening might have benefits. Certain subgroups on aspirin should be screened for HP.
References:
- García Rodríguez, LA ∙ Martín-Pérez, M ∙ Hennekens, CH ∙ et al. Bleeding risk with long-term low-dose aspirin: a systematic review of observational studies PLoS One. 2016; 11, e0160046
- Dahal, K ∙ Sharma, SP ∙ Kaur, J ∙ et al. Efficacy and safety of proton pump inhibitors in the long-term aspirin users: a meta-analysis of randomized controlled trials Am J Ther. 2017; 24:e559-e569
- Chan, FK ∙ Kyaw, M ∙ Tanigawa, T ∙ et al. Similar efficacy of proton-pump inhibitors vs H2-receptor antagonists in reducing risk of upper gastrointestinal bleeding or ulcers in high-risk users of low-dose aspirin Gastroenterology. 2017; 152:105-110.e1
- Szabó, IL ∙ Mátics, R ∙ Hegyi, P ∙ et al. PPIs prevent aspirin-induced gastrointestinal bleeding better than H2RAs. A systematic review and meta-analysis J Gastrointestin Liver Dis. 2017; 26:395-402
- Stack, WA ∙ Atherton, JC ∙ Hawkey, GM ∙ et al. Interactions between Helicobacter pylori and other risk factors for peptic ulcer bleeding Aliment Pharmacol Ther. 2002; 16:497-506
- Lanas, A ∙ Fuentes, J ∙ Benito, R ∙ et al. Helicobacter pylori increases the risk of upper gastrointestinal bleeding in patients taking low-dose aspirin Aliment Pharmacol Ther. 2002; 16:779-786
- Ng, JC ∙ Yeomans, ND Helicobacter pylori infection and the risk of upper gastrointestinal bleeding in low dose aspirin users: systematic review and meta-analysis Med J Aust. 2018; 209:306-311
- Hawkey, ChrisMant, David CA et al. Helicobacter pylori eradication for primary prevention of peptic ulcer bleeding in older patients prescribed aspirin in primary care (HEAT): a randomised, double-blind, placebo-controlled trial. The Lancet, Volume 400, Issue 10363, 1597 – 1606
- Yaslianifard S, Sameni F, Kazemi K, et al. Beyond the gut: a comprehensivemeta-analysis on Helicobacter pylori infection and cardiovascular complications. Ann Clin Microbiol Antimicrob. 2025; 24(1):18.
- Hofmann R, James S, Sundqvist MO, et al. Helicobacter pylori Screening After Acute Myocardial Infarction: The Cluster Randomized Crossover HELP-MI SWEDEHEART Trial. JAMA. 2025 Sep 1:e2515047.
- Congedi J, Williams C, Baldock KL. Epidemiology of Helicobacter pylori in Australia: a scoping review. PeerJ. 2022 May 31;10:e13430.