Long-term heartburn medication use tied to higher risk of early death

Long-term use of a class of drugs that treat heartburn may be linked to a shortened lifespan, but doctors still need to determine if the risk of using proton pump inhibitor medication outweighs the benefits for individuals.  

The class of medications includes Omeprazole (Losec), esomeprazole (Nexium) and lansoprazole (Prevacid), and at a lower dose, the over-the-counter drug Olex.

Millions of Canadians take these drugs to reduce the symptoms of heartburn, ulcer and other gastrointestinal problems by lowering the amount of acid in the stomach. They work by turning off pumps that produce acid in the stomach.

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PPI drugs are widely considered safe in the short term — under two months. 

Previous studies suggest long-term use is associated with problems including kidney damage, C. difficile infections, bone fractures and dementia. 

Recognizing those risks, Dr. Ziyad Al-Aly, an assistant professor of medicine at Washington University School of Medicine in St. Louis, and his colleagues checked to see if the drugs are also associated with higher risk of death.

"We quantitated the risk of death, and it was about 25 per cent," Al-Aly said in an interview. "What that really translates to is that if 500 patients took the medication for about a year, then there would be one excess death that could be attributed to using this class of medication called PPI."

Al-Aly called the risk small but significant since such a large number of people in the U.S. and Canada are on these medications.

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To conduct the study, researchers combed through medical records of about 275,000 new users of PPI drugs and nearly 75,000 people who started another class of drugs, called H2 blockers, to reduce stomach acid. The administrative data came from the U.S. Department of Veterans Affairs and researchers followed half the participants for at least five years.

Long-use use flagged

In Tuesday's issue of BMJ Open, Al-Aly and his co-authors evaluated the relationship between how long people took PPI drugs and risk of death, and found a higher risk of death with longer use.

The researchers cautioned that the results should not deter prescribing and use of PPI when there's a clear medical reason for them.

"These medications in the right context when patients need them, they actually could save lives," Al-Aly said.  "So what we generally advocate is a very careful risk/benefit analysis in each individual to determine if the risk outweighs the benefit in any individual patient. That naturally has to be done by their physician."

The study's authors also suggested that regularly reviewing use of prescription and over-the-counter medications could be worthwhile.

For instance, they pointed to previous U.S. studies which estimate that between half to 69 per cent of PPI prescriptions are for "inappropriate indications."

Check root cause of heartburn

Choosing Wisely Canada's gastroenterology list of Five Things Physicians and Patients Should Question also includes: "Don't maintain long term Proton Pump Inhibitor (PPI) therapy for gastrointestinal symptoms without an attempt to stop/reduce PPI at least once per year in most patients."

In some cases, addressing the root cause of heartburn, such as by losing weight, reducing alcohol, quitting smoking and making diet changes, can quell or reduce symptoms before jumping to medications, Al-Aly said.

If PPI or other acid-suppressing medications are needed, doctors suggest taking it for the shortest duration at the lowest dose required to control symptoms.

The study was based on data from mostly older white male U.S. veterans who provided demographic information. Administrators routinely collected death information.

The researchers said it's unclear how the PPI drugs would act to affect mortality. Studies on human cells suggest that the drugs could impair lysosomes that help cells to break down waste and other materials.