Potential risks associated with some commonly used drugs among older people in institutional settings - focus on proton pump inhibitors and drugs with anticholinergic properties

Background: Frail older people in institutional settings are known to suffer from comorbidities and are often administered a high number of concomitant drugs. They are therefore prone to polypharmacy, adverse drug effects, and drug-drug interactions (DDIs). Older people living in assisted living represent a particularly frail segment of the elderly population, and a large proportion of them suffer from cognitive impairment. During the last decade knowledge has accumulated on the adverse effects of drugs with anticholinergic properties (DAPs) and long-term use of protonpump inhibitors (PPIs) among older people. Less is known about the extent and prevalence of these effects among the frailest older people in institutional settings. Residents in assisted living facilities are often taken care of by consulting primary care physicians. Therefore, they may have rare opportunities for a thorough reassessment of their medication after admission to institutional care. Thus, their use of drugs intended to be taken over a limited period is often extended. Aims: This study explores the associations of DAPs and PPIs with adverse effects and investigates potentially severe DDIs among older residents in institutional settings. Of particular interest were adverse effects and mortality associated with the use of PPIs (Studies 1 and 2). In addition, concomitant use of DAPs and acetylcholinesterase inhibitors (ChEIs) and their association with psychological well-being (PWB) were investigated (Study 3). Finally, the prevalence of potentially severe D-class drug-drug interactions (DDDIs) and their association with mortality were clarified (Study 4). Methods: This study consists of four substudies. Study 1 includes 1987 residents (mean age 83.7 years, 80.7% women) from a project investigating the nutrition of nursing homes in Helsinki in 2003. Study 2 consists of three samples from various institutional settings: 1389 residents in 69 assisted living facilities in 2007 (first cohort; mean age 82.7 years, 78.9% women), 1004 residents of long-term care hospitals in 2003 (second cohort; mean age 81.3 years, 75.3% women), and 425 residents in acute geriatric wards or in nursing homes in 1999-2000 (third cohort; mean age 86.1 years, 81.6% women) in Helsinki. Study 3 investigates 1475 residents (mean age 82.8 years, 77.7% women) from a project assessing nutrition in assisted living facilities in the metropolitan area of Finland. In Study 4, these same residents were followed up for mortality for 3 years. Those 1327 residents having complete follow-up data available were included (mean-age 82.7 years, 78.3% women). In all studies participants were interviewed by trained nurses. Demographics were retrieved from medical records. Drug use and medical diagnoses were confirmed from medical records, and drugs were coded with the WHO Anatomical Therapeutic Chemical Classification System. All DAPs were classified according to the Anticholinergic Risk Scale (Study 3). Mini Nutritional Assessment (MNA) was used for evaluating nutritional status, Clinical Dementia Rating (CDR) for assessing dementia and disability, PWB scale for exploring residents’ well-being, and Charlson comorbidity index (CCI) for assessing the severity and burden of diseases. Swedish, Finnish, Interaction X-referencing database (SFINX) was used to detect DDDIs (Study 4). Mortality data were retrieved from central records in Studies 2 and 4. Results: Of nursing home residents in Study 1, 22% were administered proton-pump inhibitors (PPIs) on a daily basis. Regular PPI use was associated with diarrhoea, prior hip fracture, coronary heart disease, and lactose intolerance, indicating possible side effects or use for an inappropriate therapeutic intent. In Study 2, the prevalence of the use of PPIs varied from 21.4% (geriatric wards and nursing homes) to 26.4% (assisted living facilities). The use of PPIs was not associated with mortality among residents in assisted living facilities. However, their use was associated with increased mortality in settings where residents experienced higher levels of disability and comorbidities (long-term hospitals, geriatric wards, and nursing homes), and thus, possible higher vulnerability to adverse drug events (ADEs) of PPIs. In the acute geriatric hospital and nursing home cohort, the risk for mortality was HR 1.90 (95% CI 1.23 to 2.94) even after adjustment for age, gender, comorbidities, delirium, and use of aspirin and selective serotonin reuptake inhibitors. In Study 3, 41.6% of residents were administered DAPs. Of residents in assisted living facilities, 10.7% were administered ChEIs and DAPs concomitantly. DAP use was associated with use of a higher number of drugs, more severe disability, depression, psychiatric disorders, and Parkinson ́s disease. DAP use was associated with low psychological wellbeing even after adjustment for age, gender, education, comorbidities, and use of ChEIs. In Study 4, 5.9% of residents in assisted living facilities were susceptible to severe DDDIs. The most common DDDIs were related to use of potassiumsparing diuretics, carbamazepine and methotrexate. Residents exposed to severe DDIs were more often exposed to polypharmacy than residents not exposed to DDIs. No significant difference in mortality emerged between residents with and without DDDIs. Conclusions: The PPIs are common in institutionalized settings and they may expose to unexpected adverse effects such as diarrhoea and higher mortality among frail older people. Inappropriate use of DAPs and ChEIs concomitantly is common in assisted living facilities. DAP 8