Boston—With an increase in the use of PPIs in the past 2 decades, reports of adverse effects have burgeoned. In some cases, concerns have even been raised about whether the regular use of PPIs might contribute to mortality.

Those possibilities led to a prospective cohort study from Massachusetts General Hospital and Harvard Medical School researchers. The study team used data collected from the Nurses' Health Study (2004-2018) and the Health Professionals Follow-up Study (2004-2018).

The authors reported in Gastroenterology that among 50,156 women and 21,731 men followed for 832,026 person-years and a median of 13.8 years, 22,125 deaths were documented. These included 4,592 deaths from cancer; 5,404 deaths from cardiovascular diseases; and 12,129 deaths from other causes.

"Compared to non-users of PPIs, PPI users had significantly higher risks of all-cause mortality and mortality due to cancer, cardiovascular diseases, respiratory diseases, and digestive diseases," the researchers explained. "Upon applying lag-times of up to 6 years, the associations were attenuated and no longer statistically significant (all-cause: HR, 1.03; 95% CI, 0.96-1.10; cancer: HR, 1.06; 95% CI, 0.88-1.28; cardiovascular diseases: HR, 0.96; 95% CI, 0.82-1.12; respiratory diseases: HR, 1.14; 95% CI, 0.89-1.45; and digestive diseases: HR, 1.31; 95% CI, 0.80-2.14). Longer duration of PPI use did not confer higher risks of all-cause and cause-specific mortality."

The study concluded, "After accounting for protopathic bias, PPI use was not associated with higher risks of all-cause mortality and mortality due to major causes."

In a recent article published in Clinical Gastroenterology and Hepatology, participants in a clinical consensus conference on gastroesophageal reflux disease (GERD) recently laid out best practices for use of PPIs.

The report urges clinicians to emphasize the safety of PPIs for the treatment of GERD. It urges that patients presenting with "troublesome" heartburn, regurgitation, and/or noncardiac chest pain without alarm symptoms be prescribed a 4- to 8-week trial of single-dose PPI therapy.

"With inadequate response, dosing can be increased to twice a day or switched to a more effective acid-suppressive agent once a day," according to the guidance, which added, "When there is adequate response, PPI should be tapered to the lowest effective dose."

The analysis goes on to advise that if PPI therapy is continued in a patient with unproven GERD, clinicians should evaluate the appropriateness and dosing within 12 months after initiation. It adds that endoscopy with prolonged wireless reflux monitoring off PPI therapy should be offered to establish the appropriateness of long-term PPI therapy.

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