Islamabad - Use of proton pump inhibitors - a class of drug taken by millions to treat heartburn and reduce stomach acid - is tied to a higher risk of premature death.

“No matter how we sliced and diced the data from this large data set, we saw the same thing: there’s an increased risk of death among PPI users,” says senior author Ziyad Al-Aly, an assistant professor of medicine.

The findings add to a growing list of serious health problems tied to the use of PPIs, some of which include kidney damage, Clostridium difficile infection, bone fractures in people with osteoporosis, and dementia.

Evidence is also emerging, although it is “far from conclusive,” that PPIs may raise the risk of tissue damage resulting from oxidative stress and telomere shortening in cells. Telomeres are protective caps on the ends of chromosomes, which have been likened to the plastic ends on shoelaces that stop them unravelling.

PPIs work by reducing the amount of acid produced by the stomach. They are widely prescribed for the treatment of heartburn, or acid reflux, a condition in which stomach acid is forced back up into the food pipe, or esophagus, causing a burning sensation in the lower chest. If the condition persists, it could be a sign of a more serious problem called gastroesophageal reflux disease (GERD).

In discussing their findings, Prof Al-Aly and colleagues write that PPIs are “often overprescribed, rarely deprescribed,” and that their use is often “extended for long-term duration without appropriate medical indication.”

These were: risk of death in PPI users and users of H2 blockers; risk of death in users and non-users of PPIs; and risk of death in users of PPIs and participants who used neither PPIs nor H2 blockers. The results also showed that the risk of death went up with longer usage of PPIs.

After 30 days of use, the risk of death among PPI users was similar to that of H2 blocker users. But after 1 to 2 years of use, the risk of death among PPI users was nearly 50 per cent higher than among H2 blocker users.

Prof Al-Aly says that since millions of people take PPIs on a regular basis, this could indicate that thousands of extra deaths each year are linked to PPI use. He and his colleagues also found that the risk of death was higher among people who were using PPIs even though they appeared to have none of the gastrointestinal conditions that the drugs are recommended for. Here, the results showed that compared with H2 blocker users, PPI users had a 24 percent raised risk of death. However, the researchers say that these differences do not fully explain the higher risk of death in the PPI users, because, when they redid the statistical analysis to take out the effect of age and illness, the result remained the same. The treatment recommendation for PPIs is that they should not be taken for a long time. In the case of ulcers, for example, the typical recommendation is between 2 and 8 weeks.

However, Prof Al-Aly and colleagues note that many people can be on the drugs for months or even years.

Prof Al-Aly also says that it is often the case that doctors have a good medical reason for prescribing PPIs to their patients, but then they do not stop, instead opting to keep refilling the prescription.

He suggests that, “There needs to be periodic re-assessments as to whether people need to be on these. Most of the time, people aren’t going to need to be on PPIs for a year or 2 or 3.” He sums up the implications of the study:

“PPIs save lives. If I needed a PPI, I absolutely would take it. But I wouldn’t take it willy-nilly if I didn’t need it. And I would want my doctor to be monitoring me carefully and take me off it the moment it was no longer needed.”