May 30, 2019

Study Links Use of PPIs to Fatal Heart, Kidney Disease and Stomach Cancer

A study published in The BMJ has linked long-term use of proton pump inhibitors (PPIs) to fatal cases of cardiovascular disease, chronic kidney disease, and upper gastrointestinal cancer.

These risks increase as the use of PPI continues, even when the drugs are taken at low doses.

“Taking PPIs over many months or years is not safe, and now we have a clearer picture of the health conditions associated with long-term PPI use,” said senior author Ziyad Al-Aly, MD, Washington University School of Medicine in St. Louis, St. Louis, Missouri.

Other researchers independently have linked PPIs to adverse health problems such as dementia, bone fractures, heart disease, and pneumonia, among others.

For the current study, researchers sifted through de-identified medical records in a database maintained by the US Department of Veterans Affairs. Examining medical data acquired from July 2002 to June 2004, the researchers identified 157,625 people -- mostly Caucasian men aged 65 years and older -- who had been newly prescribed PPIs, and 56,842 people who had been newly prescribed H2 blockers. They followed the patients for up to 10 years.

The researchers found a 17% increased risk of death in the PPI group compared with the H2 blocker group. They calculated 45 excess deaths attributable to long-term PPI use per 1,000 people. Death rates for PPIs were 387 per 1,000 people, and death rates for H2 blockers were 342 per 1,000.

“Given the millions of people who take PPIs regularly, this translates into thousands of excess deaths every year,” said Dr. Al-Aly.

PPI use was associated with deaths caused by cardiovascular disease, chronic kidney disease, and upper gastrointestinal cancer. Specifically, 15 per 1,000 of the PPI users died from heart disease, 4 per 1,000 from chronic kidney disease, and 2 per 1,000 from stomach cancer.

Death rates due to cardiovascular disease were 88 among the PPI group and 73 among the H2 blockers group. For stomach cancer, death rates were 6 in the PPI group and 4 in the H2 blockers group. Death rates due to chronic kidney disease were 8 and 4 in the PPI and H2 blocker groups, respectively.

In addition, more than half of the people taking PPIs did so without a medical need, although the data did not indicate why the patients had been prescribed PPIs. Among this group, PPI-related deaths were more common, with almost 23 people per 1,000 dying from heart disease, almost 5 per 1,000 from chronic kidney disease, and 3 from stomach cancer.

“Most alarming to me is that serious harm may be experienced by people who are on PPIs but may not need them,” said Dr. Al-Aly. “Overuse is not devoid of harm.”

The study also found that more than 80% of PPI users were on low doses of the prescription drug, or those equivalent to doses offered in over-the-counter versions.

“This suggests the risk may not be limited to prescription PPIs, but it also may occur at over-the-counter doses,” said Dr. Al-Aly.

The team will continue to study adverse health effects related to PPIs, in particular regarding those at the highest risk.

“A lot of people may be taking PPIs unnecessarily,” said Dr. Al-Aly. “These people may be exposed to potential harm when it is unlikely the drugs are benefiting their health. Our study suggests the need to avoid PPIs when not medically necessary. For those who have a medical need, PPI use should be limited to the lowest effective dose and shortest duration possible.”

Reference: http://dx.doi.org/10.1136/bmj.l1580

SOURCE: Washington University in St. Louis
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