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Proton pump inhibitors linked to fatal cases of
CVD, CKD, stomach cancer
May 31, 2019
People who take popular
heartburn drugs like Prevacid, Prilosec and Nexium are vulnerable to death from
cardiovascular disease, chronic kidney disease (CKD) and upper gastrointestinal
cancer, according to new research published in The BMJ. The drugs’ negative effects were
most pronounced in those who were taking them long-term without a clear
indication, even at low doses.
Senior author Ziyad Al-Aly, MD, and colleagues studied
over-the-counter and prescription solutions for heartburn, acid reflux and
ulcers—also known as proton pump inhibitors (PPIs)—because in the past they’ve
been linked to health issues like dementia, bone fractures and pneumonia. Since
they’re one of the most commonly used drug classes in the U.S., prescribed to
upwards of 15 million Americans, adverse side effects could have wide-reaching
implications.
“Identification of specific causes of death attributable to
taking PPIs will inform the public about the risk of taking PPIs in the long
term and could inform risk stratification, risk mitigation strategies and help
shape the development of deprescription interventions to reduce unnecessary or
un-indicated PPI use,” Al-Aly, an assistant professor at the Washington
University School of Medicine in St. Louis, and co-authors wrote.
For their research, Al-Aly et al. sorted through de-identified
medical records maintained by the U.S. Department of Veterans Affairs between
2002 and 2004. They pulled information for 157,625 patients who’d been newly
prescribed PPIs and 56,842 people who’d been newly prescribed another class of
acid-suppressants, H2 blockers (Zantac, Pepcid and Tagamet are a few brand-name
examples).
After a decade of follow-up, the researchers identified a 17%
increased risk of death in the PPI group compared with the H2 blocker group,
with an excess 45 deaths per 1,000 people attributable to long-term PPI use.
Death rates as a whole were 387 per 1,000 people for PPIs and 342 per 1,000
people for H2 blockers.
The authors said that among people who took PPIs, 38.7% of
deaths were related to circulatory system diseases, 28.6% to neoplasms, 13.8%
to genitourinary system diseases and 9.3% to infectious and parasitic diseases.
Analyses by subcauses of death revealed new use of PPIs was associated with
excess mortality from CVD and CKD.
Patients who took PPIs but did so without a medical need—which
was more than half of the PPI population—saw the highest death rate from
PPI-related causes. In that subset of patients nearly 23 people per 1,000 died
of heart disease, 5 per 1,000 died from CKD and 3 per 1,000 died from stomach
cancer. Risk seemed to increase with longer-term use of the drugs, even if they
were taken at low doses, as was the case for 80% of users.
“Overuse of proton pump inhibitors is not devoid of harm,”
Al-Aly and Yan Xie, a biostatician at the Department of Veterans Affairs St.
Louis Health Care System, wrote in a BMJ blog. “The totality of the results suggests
the need to avoid proton pump inhibitors when not medically indicated; for
those who have a medical indication for PPIs, use should be limited to the
lowest effective dose and shortest duration possible.”
Al-Aly et al.’s work has reportedly drawn interest from the U.S.
FDA, according to the University of Washington.
“PPIs sold over the-counter should have a clearer warning about
potential for significant health risks, as well as a clearer warning about the
need to limit length of use, generally not to exceed 14 days,” he said in a release. “People who feel the need to take
over-the-counter PPIs longer than this need to see their doctors.”
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