PPIs, Mortality, and Rehospitalization in Older Patients Post Hospitalization
RESEARCH · April 01, 2013
TAKE-HOME MESSAGE
- Use of proton pump inhibitors (PPIs) is associated with an increased risk of all-cause mortality in older patients discharged from acute care hospitals, even after adjusting for established predictors of adverse outcomes in this population, for whom physicians need to balance the benefits and risks of long-term high-dose PPI use.
SUMMARY
PracticeUpdate Editorial Team
In the past 2 decades, the use of proton pump inhibitors (PPIs) has increased dramatically, particularly in older individuals. This may be due, in part, to the superiority of PPIs over histamine receptor antagonists in the treatment of gastroesophageal reflux disease (GERD) and peptic ulcers, which are frequently more critical disorders in older patients.
Recently, studies have suggested an increased risk of fractures, community-acquired pneumonia, and Clostridium difficile infections with long-term PPI use. The properties of PPIs, including mechanism of action and potential for drug interactions; the general health of older persons (eg, nutritional status, comorbidities); and inappropriate prescribing contribute to the risks associated with long-term PPI use in this population.
In two recent studies, PPI use was associated with increased mortality in older patients who were institutionalized or after discharge from the hospital. The present study investigated the association between PPI use and the risk of death, or the combined endpoint of death or rehospitalization, in older patients discharged from acute care hospitals.
Mortality and the combined endpoint of death or rehospitalization were investigated in a cohort from the observational Italian Pharmacosurveillance in the Elderly Care study in patients aged ≥ 65 years consecutively admitted to acute care medical wards from April through June 2007. The study cohort comprised 491 patients (mean age, 80 years; 46% men) with complete baseline and follow-up data; 317 were nonusers and 174 were PPI users.
Cognitive impairment (Mini-Mental State Examination score < 24: 62.6% vs 43.5%), overall comorbidity, and prescription drug use was significantly greater (P = .001 for all) in PPI users than in nonusers. Fewer nonusers than PPI users at baseline died during the 1-year follow-up (10.4% vs 18.4%). Similarly, when the combined endpoint was considered, fewer nonusers than PPI users at baseline died or were rehospitalized during the follow-up period (18.6% vs 30.5%). Incidence rates for mortality (21.5 vs 12.0; P = .009) or the combined endpoint of death or rehospitalization (39.8 vs 22.9; P = 003) were higher in PPI users than in nonusers.
According to time-dependent Cox proportional hazards regression, hazard ratios (adjusted for age, sex, body mass index, hypoalbuminemia, cognitive impairment, dependency in activities of daily living, GERD, peptic ulcer, diarrhea, infectious disease, fracture, polypharmacy at discharge, and antithrombotic or nonsteroidal anti-inflammatory drug use) showed that the use of PPIs was independently associated with mortality, 1.51 (95% CI, 1.03−2.77; P = .03) but not with the combined endpoint of death or rehospitalization, 1.49 (95% CI, 0.98−2.17; P = .11). The risk of 1-year mortality was significantly increased in patients exposed to high-dose PPIs vs none, 2.59 (95% CI, 1.22−7.16; P = .007); however, a similar association was not seen when the combined endpoint was considered.
In agreement with recent findings, this study showed that the use of PPIs is associated with an increased risk of all-cause mortality, but not the combined endpoint of mortality or rehospitalization, in older patients discharged from acute care hospitals, even after adjusting for established predictors of adverse outcomes including age, cognitive impairment, disability, comorbidities, drugs known to interact with PPIs, polypharmacy, and nutritional status. Randomized controlled studies of PPI use in older patients are warranted. Physicians need to balance the benefits and risks of long-term high-dose PPI use in this population.
JAMA internal medicine
Proton Pump Inhibitors and Risk of 1-Year Mortality and Rehospitalization in Older Patients Discharged From Acute Care Hospitals
JAMA Intern Med 2013 Apr 01;173(7)518-523, M Maggio, A Corsonello, GP Ceda, et al