PPI users with those who took neither PPIs nor H2 blockers.
"A lot of times people get prescribed PPIs for a good medical reason, but then doctors do not stop it and patients just keep getting refill after refill", Al-Aly said. "We don't want to leave people with a scary message".
Short-term use of PPIs - up to 90 days - did not appear to affect death risk, the findings showed. Previous studies have tied the drugs to kidney problems, dementia, and bone fractures, although not all research has agreed.
The other analyses revealed a similar level of risk between users and non-users of PPIs and between those taking PPIs and those taking no acid suppressant drugs.
With so many studies associating PPIs with other health risks, researchers from Washington University School of Medicine in St. Louis wanted to find out if people who took the drugs were at greater risk of dying. He suggests that doctors perform re-assessments periodically to check whether people still need to be taking the drugs because in most cases, people are not going to be needing them for two or three years at a time. The researchers calculate that, for every 500 people taking PPIs for a year, there is one extra death that would not have otherwise occurred.
The people who took PPIs had a 25 percent higher risk of early death. This increased the longer PPIs were taken.
The study "did not look at OTC products, rather, it only involved prescription (proton-pump inhibitors) which are typically used at higher doses and for longer durations", said Anita Brikman, senior vice president at Consumer Healthcare Products Association, a trade organization representing over-the-counter drug manufacturers.
Even though this study could not prove a direct cause-and-effect relationship, Al-Aly noted that the increased risk with longer duration adds weight to concerns over the drugs' safety.
"This finding is certainly cause for concern and something that should be considered as doctors continue to prescribe PPIs at a high rate and often fail to discontinue these drugs in a timely fashion", said Dr. Louis Cohen. They say that limited use only when medically necessary is best.
Recommended treatment regimens for most PPIs are relatively short, the researchers said.
But those who used PPIs were also more likely to use anticholinergic medicines that have been linked to thinking difficulties.
But since the drugs are available over-the-counter, many people take PPIs for months or years to manage heartburn or acid reflux, Al-Aly said. The research is published online July 3 in the journal BMJ Open.
Al-Aly emphasizes that deciding whether to take a PPI requires a risk-benefit calculation.
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".