Proton-Pump Inhibitors Associated with Increased Mortality Risk


Clinical question: Is the use of proton-pump inhibitors (PPIs) associated with risk of mortality or combined risk of death or rehospitalization in older patients discharged from acute-care hospitals?

Background: Previous studies have shown that the use of PPIs could be associated with increased mortality in institutionalized older people and in patients discharged from acute-care hospitals. Older patients could be more vulnerable to adverse effects of PPIs, such as drug-drug interactions and absorption of nutrients, because of the higher incidence of polypharmacy and malnutrition in the elderly.

Study design: Prospective cohort.

Setting: Eleven acute-care medical wards participating in the Italian study Pharmacosurveillance in the Elderly Care.

Synopsis: All patients aged 65 years or older consecutively admitted to participating wards from April to June 2007 underwent screening. Excluding patients who refused, died during hospitalization, or were admitted to long-term care or rehabilitation units, a total of 491 patients were analyzed. The study team administered questionnaires during admission and conducted follow-up visits every three months for one year after discharge. Outcomes included one-year survival of patients discharged from acute-care medical wards and the combined endpoint of death or rehospitalization.

Overall, 174 patients (35.4%) had PPI exposure. After adjusting for age, cognitive impairment, disability, comorbidities, nutritional status, and number of drugs prescribed, patients exposed to PPIs had a significantly increased risk of death (adjusted HR 1.51, 95% CI 1.03-2.77). This association was strongest among patients receiving high-dose PPIs. No such association was found when considering the combined endpoint (HR 1.49, 95% CI 0.98-2.17). Limitations of the study include observational design, small size, potential for confounding by indication for PPI, and indeterminate PPI use prior to index hospitalization. Finally, the finding of an association between PPIs and increased mortality does not equate to a causative relationship between the two variables.

Bottom line: Proton-pump inhibitor use in older patients discharged from acute-care hospitals is associated with increased all-cause mortality at one year.

Citation: Maggio M, Corsonello A, Ceda GP, et al. Proton-pump inhibitors and risk of 1-year mortality and rehospitalization in older patients discharged from acute care hospitals. JAMA Intern Med. 2013;173(7):518-523.

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