Disclosures: Mahmud reports receiving support from the NIH/National Institute of Diabetes and Digestive and Kidney Diseases. Please see the study for all other authors’ relevant financial disclosures.
May 03, 2022
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PPI use should be limited to appropriate indications, lowest effective dose in cirrhosis

Disclosures: Mahmud reports receiving support from the NIH/National Institute of Diabetes and Digestive and Kidney Diseases. Please see the study for all other authors’ relevant financial disclosures.
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Although proton pump inhibitors were linked with an increased risk for infection and decompensation in patients with cirrhosis, they may still be of benefit in those with prior gastrointestinal bleeding, according to published data.

“In this study we found that proton pump inhibitor use was associated with liver-related adverse events that may mediate liver-related mortality,” Nadim Mahmud, MD, MS, MPH, MSCE, assistant professor of medicine and epidemiology at the University of Pennsylvania Perelman School of Medicine, told Healio. “However, in patients who had a prior hospitalization with gastrointestinal bleed, PPIs were associated with reduced mortality. This suggests that in the presence of an appropriate indication, such as peptic ulcer-related bleeding, PPIs are important and may confer a mortality benefit.”

HGI0522Mahmud_Graphic_01_WEB

In a retrospective study published in Gastroenterology, Mahmud and colleagues included 76,251 patients with cirrhosis in the Veterans Health Administration, 23,628 of whom were on a PPI at study onset. Investigators classified PPI exposure as a time-updating variable from the index time of cirrhosis diagnosis and analyzed data after adjusting for time-varying covariates, including cardiovascular comorbidities, gastrointestinal bleeding and statin exposure.

According to study results, binary PPI exposure correlated with reduced all-cause mortality in patients hospitalized for GI bleeding (HR = 0.88; 95% CI, 0.84-0.91) but did not significantly associate with the other covariates (HR = 0.99; 95% CI, 0.97-1.02). Conversely, cumulative PPI exposure correlated with increased mortality in patients without hospitalization for GI bleeding (HR = 1.07 per 320 mg-months [omeprazole equivalents]; 95% CI, 1.06-1.08). PPI exposure also correlated with severe infection (HR = 1.21; 95% CI, 1.18-1.24) and decompensation (HR = 1.64; 95% CI, 1.61-1.68).

Further, results from cause-specific mortality analysis showed PPI exposure was associated with increased liver-related mortality (HR = 1.23; 95% CI, 1.19-1.28) but with decreased non-liver-related mortality (HR = 0.88; 95% CI, 0.85-0.91).

“Our study would argue that in patients with cirrhosis, PPIs should not be avoided solely because of concerns regarding liver-related adverse events,” Mahmud continued. “However, prescriptions should be limited to appropriate indications at the lowest effective dose.”