Earlier research has already warned that taking a proton pump inhibitor (PPI) drug long-term can potentially shorten life. Now new research has discovered the three leading causes of death from PPI use. If your doctor tells you that you need to take a PPI—for instance, because you have GERD or an ulcer—here’s what you need to know and do to protect your health.

PPIs have been around for more than 25 years. They work by blocking stomach cells from secreting acid and are very effective for treating gastroesophageal reflux disease (GERD), ulcers and inflammation of the esophagus or stomach. Because they work so well and had seemed safe, they were made available in drugstores without a prescription. Millions of people now use these drugs to treat minor heartburn symptoms. The problem is that they use them for months or even years—while they are meant to be used for only up to two weeks.

In 2017, a study led by Washington University School of Medicine in St. Louis found that people taking a PPI had a 15% increased risk for death compared with those not taking a PPI. And compared with people taking an H2 blocker (another kind of heartburn medication), those who took a PPI were at a 25% increased risk for death.

Now, a new study from the same researchers and the Veterans Affairs St. Louis Health Care System pins down the causes of increased deaths from PPI use.

The study looked at 10 years of medical records for nearly 160,000 patients in the Veterans Affairs Health Care System who were newly prescribed more than a 90-day supply of a PPI and about 60,000 veterans who were prescribed more than a 90-day supply of an H2 blocker in the six months after starting the drugs.


  • Patients taking PPIs longer than 90 days had a 17% higher risk for death than patients on H2 blockers. For every 1,000 patients, 45 excess deaths were attributed to long-term use of PPIs. By contrast, no increased risk for death was found for taking H2 blockers.
  • Increased risk for death started after about one year of PPI use and rose as use continued over time.
  • In order of frequency, causes of death were cardiovascular disease, chronic kidney disease and upper gastrointestinal cancers (such as stomach) —and these deaths were not associated with having a history of any of these conditions.
  • According to their medical records, PPI use was not even properly indicated for more than half the patients when they started on the drugs. (The study did not look at indications for H2 blocker use.)
  • 80% of the patients’ prescriptions were at the low-dose level found in OTC PPIs.

Exactly how PPIs cause deadly cardiovascular disease, kidney disease and upper GI cancer is not completely understood.

Millions of people now take an OTC PPI, and researchers are concerned that many of them are taking these drugs for longer than two weeks…and for symptoms that do not need a PPI. They advise doctors to prescribe these drugs only for conditions that warrant their use—such as to stop the bleeding in a bleeding ulcer or to treat Barrett’s esophagus and only at the lowest dose and for the shortest time needed to treat the condition.

Heartburn is not a disease. It is a symptom. If you decide to take an OTC PPI for heartburn, don’t take it for more than two weeks at a time. If you need help with your heartburn longer than that or frequently, talk to your doctor about what is causing your symptoms. It could be an ulcer, gastroesophageal reflux disease, smoking, your diet or being overweight. If your doctor prescribes a PPI for more than two weeks, ask your doctor if you really need it…or if there is a safer alternative, such as an H2 blocker (OTC brand: Pepcid) or an antacid (Mylanta, Rolaids, Tums) for occasional heartburn. Also ask about lifestyle and/or dietary changes that might reduce your heartburn. And if you must take a PPI for a long time, take the lowest effective dose and make sure your doctor is monitoring your kidney function and your heart and is screening you for cancer.  

Related Articles