Proton Pump Inhibitors Linked To Higher Death Risk

Longtime use of proton pump inhibitors is associated with an increased risk of death, a new study from Washington University School of Medicine in St. Louis reports. The widely used heartburn drugs have previously been linked to a variety of health problems, including serious kidney damage, bone fractures and dementia.

Millions of U.S. residents take proton pump inhibitors (PPIs) which are prescribed to treat heartburn, ulcers and other gastrointestinal problems. The drugs also are available over the counter under brand names that include Prevacid, Prilosec and Nexium.

The study used medical records of some 275,000 users of PPIs and nearly 75,000 people who took another class of drugs – known as H2 blockers – to reduce stomach acid.

“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. For example, when we compared patients taking H2 blockers with those taking PPIs for one to two years, we found those on PPIs had a 50 percent increased risk of dying over the next five years. People have the idea that PPIs are very safe because they are readily available, but there are real risks to taking these drugs, particularly for long periods of time,”

said senior author Ziyad Al-Aly, MD, an assistant professor of medicine.

25% Increased Risk

A kidney doctor by profession, Al-Aly has previously published studies linking PPIs to kidney disease, and other researchers have shown an association with other health problems. Al-Aly, first author Yan Xie, PhD, a data scientist, and colleagues reasoned that since each of these side effects carries a small risk of death, together they may affect the mortality rate of PPI users.

To find out, the researchers sifted through millions of de-identified veterans’ medical records in a database maintained by the U.S. Department of Veterans Affairs.

They identified 275,933 people who had been prescribed a PPI and 73,355 people prescribed an H2 blocker between October 2006 and September 2008, and noted how many died and when over the following five years. The database did not include information on cause of death.

Al-Aly and colleagues found a 25 percent increased risk of death in the PPI group compared with the H2 blocker group.

The researchers calculate that, for every 500 people taking PPIs for a year, there is one extra death that would not have otherwise occurred. Given the millions of people who take PPIs regularly, this could translate into thousands of excess deaths every year, Al-Aly said.

Longer Term Use Risks Higher

The researchers also calculated the risk of death in people who were prescribed PPIs or H2 blockers despite not having the gastrointestinal conditions for which the drugs are recommended. Here, the researchers found that people who took PPIs had a 24 percent increased risk of death compared with people taking H2 blockers.

Further, the risk rose steadily the longer people used the drugs. After 30 days, the risk of death in the PPI and H2 blocker groups was not significantly different, but among people taking the drugs for one to two years, the risk to PPI users was nearly 50 percent higher than that of H2 blocker users.

Although the recommended treatment regimen for most PPIs is short – two to eight weeks for ulcers, for example – many people end up taking the drugs for months or years.

“A lot of times people get prescribed PPIs for a good medical reason, but then doctors don’t stop it and patients just keep getting refill after refill after refill,” Al-Aly said. “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 two or three.”

As compared with the H2 blocker group, people in the PPI group were older (64 years old, on average, versus 61) and also somewhat sicker, with higher rates of diabetes, hypertension and cardiovascular disease. But these differences cannot fully account for the increased risk of death since the risk remained even when the researchers statistically controlled for age and illness.

Over-the-counter PPIs contain the same chemical compounds as in prescription PPIs, just at lower doses, and there is no way to know how long people stay on them. The Food and Drug Administration recommends taking PPIs no longer than four weeks before consulting a doctor.

Al-Aly emphasizes that deciding whether to take a PPI requires a risk-benefit calculation.

“PPIs save lives,” he says. “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.”

Yan Xie, Benjamin Bowe, Tingting Li, Hong Xian, Yan Yan, Ziyad Al-Aly
Risk of death among users of Proton Pump Inhibitors: a longitudinal observational cohort study of United States veterans
BMJ Open Jun 2017, 7 (6) e015735; DOI: 10.1136/bmjopen-2016-015735

Image: Robert Boston

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