Millions of people taking common heartburn and indigestion medications could be at an increased risk of death, research suggests.

The drugs, known as proton pump inhibitors (PPIs), neutralise the acid in the stomach and are widely prescribed, with low doses also available without prescription from pharmacies. In the UK, doctors issue more than 50m prescriptions for PPIs every year.

Now researchers say the drugs can increase risk of death, both compared with taking a different type of acid suppressant and not taking any at all.

“We saw a small excess risk of dying that could be attributed to the PPI drug, and the risk increased the longer they took them,” said Ziyad Al-Aly, an epidemiologist from the University of Washington and co-author of the study.

The team say the study suggests those who take the drugs without needing to could be most at risk. They urged people taking PPIs to check whether this was necessary.

Previous research has raised a range of concerns about PPIs, including links to kidney disease, pneumonia, more hip fractures and higher rates of infection with C difficile, a superbug that can cause life-threatening sepsis, particularly in elderly people in hospitals.

But the latest study is the first to show that PPIs can increase the chance of death. Published in the journal BMJ Open, it examined the medical records of 3.5 million middle-aged Americans covered by the US veterans healthcare system.

The researchers followed 350,000 participants for more than five years and compared those prescribed PPIs to a group receiving a different type of acid suppressant known as an H2 blocker. They also took into account factors such as the participants’ age, sex and conditions ranging from high blood pressure to HIV.



The results show that those who took PPIs could face a 25% higher risk of death than those who took the H2 blocker.



“In patients on [H2 blocker] tablets, there were 3.3 deaths per 100 people over one year. In the PPI group, this figure was higher at 4.7 per 100 people per year,” said Al-Aly.

The team also reported that the risk of death for those taking PPIs was 15% higher than those taking no PPIs, and 23% higher than for those taking no acid suppressants at all.

Similar levels of increased risk were seen among people who used PPIs but had no gastrointestinal conditions, a result which the authors speculated might be driving the higher risk seen overall.

Gareth Corbett, a gastroenterologist from Addenbrooke’s hospital in Cambridge who was not involved with the study, cautioned against panic, pointing out that in most cases the benefits of PPI far outweighed any risk. What was more, he said, while the increased risk sounded high, it was still very low for each person.



“PPIs are very effective medicines, proven to save lives and reduce the need for surgery in patients with bleeding gastric and duodenal ulcers and several other conditions,” he said.



The study’s authors said it was important that PPIs were used only when necessary and stopped when no longer needed.

Corbett agreed that many people take PPIs unnecessarily. “They could get rid of their heartburn by making lifestyle changes, such as losing weight and cutting back on alcohol, caffeine and spicy foods,” he said.

The authors said the study was observational, meaning it did not show that PPIs were the cause of the increased risk of death, and that it was unclear how the drugs would act to affect mortality. They said the drugs could affect components within cells, known as lysosomes, that help break down waste material, or shortening protective regions at the end of chromosomes, known as telomeres.

Aly said people on PPIs should check with their GP whether the drugs were still needed, adding: “In some cases we expect that PPIs can be safely stopped, particularly in patients who have been taking them for a long time.”