The study did not look at the use of PPI drugs that you can buy over the counter.
Still, the study is only an association - it doesn't prove cause and effect.
Despite the findings, "there are some patients out there who could benefit from PPIs", Al-Aly says.
For the new study, published in the BMJ Open, researchers examined data involving more than six million people whose health was tracked for an average of six years - until 2013 or death, whichever came first.
"The VA has the largest integrated electronic medical record system in the world", Al-Aly said. "Most of the time, people aren't going to need to be on PPIs for a year or 2 or 3".
Given the millions of people who take PPIs regularly, this could translate into thousands of excess deaths every year, Al-Aly said.
'They are an effective and appropriately safe way to provide short-term relief from heartburn and indigestion, if used in accordance with the clear on-pack instructions and the patient information leaflet inside'.
Al-Aly and colleagues found a 25 percent increased risk of death in the PPI group compared with the H2 blocker group.
"However we looked at the data, there was a consistent [link] with PPI use and risk of death", Al-Aly says.
Previous studies suggest long-term use is associated with problems including kidney damage, C. difficile infections, bone fractures and dementia. It is these genetic differences that may contribute to earlier deaths. "Limiting PPI use and duration to instances where it is medically indicated may be warranted".
"We are confident in the safety and efficacy of Nexium and Prilosec when used in accordance with the FDA approved label, which has been established through numerous clinical trials", said Alexandra Engel, a spokeswoman for AstraZeneca, which was not involved in the new study. The association was also not involved in the research. But these differences can not fully account for the increased risk of death since the risk remained even when the researchers statistically controlled for age and illness.
Popular heartburn drugs known as proton pump inhibitors may raise the chance of death, new research shows.
Dr. Ihab Hajjar, an associate professor at the Emory University School of Medicine, said the new findings are "concerning".
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".
He urges patients and doctors to be mindful of why they're using a medication.
Further, the risk rose steadily the longer people used the drugs.
One doctor said the results should be heeded. Perhaps for this reason, Hajjar and his team arrived at different conclusions than other researchers. "Risk is also increased among those without gastrointestinal conditions and with prolonged duration of use".
By contrast, Al-Aly and his co-authors believe a "growing body of evidence" indicates that use of these drugs is associated with a "host of adverse events". The longer the use, the higher the risk, he says.