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Dec 06, 2023

Aspirin can increase stomach bleeding risk: How to reduce it?

Thanks to its wide range of medicinal benefits, aspirin is one of the most

Thanks to its wide range of medicinal benefits, aspirin is one of the most commonly used medications in the world.

For decades, aspirin has been used for the prevention of cardiovascular events in patients with heart disease. By thinning the blood, aspirin reduces the risk of blood clotting and may prevent a heart attack or a stroke.

The main disadvantage of aspirin use is the risk of serious gastrointestinal bleeding, which can occur even at low doses. A 2021 clinical trial that enrolled 19,114 participants aged 70 years or older found that aspirin increases the risk of significant gastrointestinal bleeding by 60%.

Previous studies have demonstrated a strong link between the occurrence of peptic ulcers in patients receiving low-dose aspirin — usually up to 100 milligrams (mg) daily, but may reach 325 mg daily — and the presence of Helicobacter pylori, a bacterium that infects the stomach.

H. pylori infection can result in the formation of peptic ulcers — open sores in the lining of the stomach and duodenum. Doctors believed that the anti-blood-clotting effects of low-dose aspirin increase bleeding from these peptic ulcers.

A team led by researchers from the University of Nottingham in the United Kingdom conducted a large clinical trial to investigate whether the eradication of H. pylori would protect against aspirin-associated ulcer bleeding. The results of this trial appear in The Lancet.

"In clinical practice, we see a number of patients who stop taking aspirin due to bleeding issues. So, this is a real issue," Dr. Khagendra Dahal, interventional cardiologist and assistant professor at Creighton University School of Medicine in Omaha, Nebraska, told Medical News Today.

"This is a large randomized trial and the first one, according [to] the authors, […] to address the issue of H. pylori eradication to prevent aspirin-related gastrointestinal bleeding. So, this is a commendable job to undertake this issue and try to address strategies to reduce gastrointestinal bleeding," he added.

Between September 2012 and November 2017, at 1,208 primary care centers in the U.K., the researchers recruited patients aged 60 years or older, who were receiving a daily aspirin dose of 325 mg or less, and had a positive urea breath test for H. pylori at screening. They excluded patients who were receiving ulcer-causing or gastroprotective medication.

Out of 30,166 patients tested for H. pylori, 5,367 had a positive result. A total of 5,352 of these patients were randomly assigned to receive either H. pylori eradication medication — a combination of oral clarithromycin 500 mg, metronidazole 400 mg, and lansoprazole 30 mg (2,677 participants) — or an oral placebo (2,675 participants), twice daily for 1 week.

The study was double-blinded, which means that neither the participants, their healthcare providers, nor the researchers knew which treatment group — whether active eradication or placebo — each participant was assigned to.

The researchers followed up on the participants’ health outcomes for a median of 5 years by assessing their electronic health data.

As expected, H. pylori eradication was associated with a significant reduction in the risk of hospitalization for ulcer bleeding. There were six episodes of definite or probable peptic ulcer bleeds in the H. pylori eradication group, compared to 17 episodes in the placebo group.

Surprisingly, the protective benefit of H. pylori eradication appeared to be lost after 2.5 years. This is "a finding that has not been observed before," according to the researchers, and warrants further investigation.

Possible explanations for this apparent loss of protection over time are enhanced acid secretion or reduced release of protective prostaglandins following H. pylori eradication, or the existence of highly recurrent idiopathic ulcers (ulcers with unknown cause).

"Although it seems surprising that a one-week course of antibiotics could have a prolonged effect, this is a well-recognized feature of Helicobacter pylori. It is thought that the infection is acquired during childhood and adolescence and persists thereafter. If it is eradicated during adult life, it is rare for reinfection to occur. We retested 10% of our subjects and found that 91% of them had a negative H. pylori breath test."

– Prof. Chris Hawkey, lead study author, and professor of gastroenterology at the Nottingham Digestive Diseases Centre, U.K.

To date, long-term aspirin users are prescribed proton-pump inhibitors or histamine H2-receptor antagonists to prevent the risk of gastrointestinal bleeding. The HEAT study has demonstrated that the eradication of H. pylori with a short course of antibiotics can be used as an alternative or complementary gastroprotective strategy.

"Their data clearly showed that just one week of H. pylori eradication therapy led to such a clinically important benefit that had lasted for at least 2.5 years," said Prof. Francis K.L. Chan, professor and dean of medicine at the Chinese University of Hong Kong, and specialist in gastroenterology.

"While one might be tempted to believe that long-term prophylactic treatment with a proton-pump inhibitor is preferred to 1 week of H. pylori eradication therapy, in real clinical practice physicians will not prescribe proton-pump inhibitors to these low-risk aspirin users because it is neither evidence-based nor cost-effective," he pointed out.

"Patient compliance to life-long co-therapy proton-pump inhibitor[s] is another challenge. It follows that test-and-treat H. pylori is a beneficial, acceptable and affordable treatment even for a huge population of average- to low-risk aspirin users who otherwise will not receive any stomach protective therapy," Prof. Chan further commented.

Besides its role in preventing heart attacks and strokes in people with increased cardiovascular risk, there is also evidence that aspirin can slow down colorectal cancer.

"We would argue that the risks of ulcer bleeding are now low and that a more liberal use of aspirin to investigate effects on health including cancer should be considered," Prof Hawkey told MNT.

In their paper, the researchers also noted that the HEAT study also develops a framework that can be used to assess other significant clinical issues in primary care.

The HEAT study is "one of the largest to be done in primary care and without funding from the pharmaceutical industry," Prof. Hawkey said in comments to MNT.

Furthermore, "the [H. pylori eradication] regimen used was a standard […] one. The antibiotics used were all generic [and] not expensive," Prof Hawkey added, suggesting that an antibiotic-based gastroprotective strategy would be accessible to all patients.

When asked about the study's limitations, Prof. Hawkey noted that "we did not study subjects who were just starting on aspirin, for logistical reasons, but this is an important group who have a somewhat higher risk of ulcer bleeding."

Another limitation is the low number of bleeding events in each arm of the study, which led to the study being terminated before the planned number of primary outcome events had occurred.

Dr. Dahal commented that "[w]hile this establishes [the] safety of aspirin in such patients, it may also question the utility of H. pylori eradication if it is only helping [a] very small number of patients out of thousands tested and treated."

Dr. Dahal also called out the fact that this study was performed in the U.K., and |its applicability in rest of the world, especially in the U.S. or in people of Asian or African origin" needs to be determined.

When asked about future studies, Prof. Hawkey told MNT that "an obvious next step would be a test and treat study at the time patients are prescribed for the first time, but given the decline in H. pylori prevalence, it might be considered a rather niche study and prescribers would probably be prepared to generalize from the results of our trial."