Prevalence and Risk of Polypharmacy among the Elderly in an Outpatient Setting: A Retrospective Cohort Study in the Emilia-Romagna Region, Italy

Background: Polypharmacy, the simultaneous taking of many medications, has been well documented and is a topic of much concern for those looking to improve the quality of care for the elderly. Elderly patients often develop complicated and multi-factorial health states that require extensive pharmacotherapy, leaving this population at risk for exposure to drug-drug interactions and other adverse events. Previous literature supports an association between an increase in the rate of adverse events as the number of drugs taken by a patient increases. Objective: We sought to evaluate the prevalence of polypharmacy, and to determine patient characteristics that are predictive of exposure to polypharmacy, in the elderly population of the Emilia-Romagna region in Italy. Methods: We conducted a retrospective cohort study of the 2007 EmiliaRomagna outpatient pharmacy database linked with patient information available from a demographic file of approximately 1 million Emilia-Romagna residents aged ≥65 years. The cohort was comprised of 887 165 elderly subjects who had at least one prescription filled during the study year. Using the World Health Organization’s defined daily dose (DDD) to determine the duration of treatment for a given drug, we defined a polypharmacy episode as overlapping treatment with five or more medications occurring for at least one day. The prevalence of polypharmacy was measured together with subject characteristics found to be predictive of polypharmacy exposure. Results: A total of 349 689 elderly people in the population (39.4%) were exposed to at least one episode of polypharmacy during the study period. The prevalence of polypharmacy substantially increased with age and with a higher number of chronic conditions. Over 35% of those exposed to polypharmacy were exposed for 101 or more days of the year. The top three classes of medications involved in polypharmacy were antithrombotics, peptic ulcer disease and gastrooesophageal reflux disease agents and ACE inhibitors. The odds of exposure to polypharmacy were higher for older subjects, males and subjects living in urban areas. Conclusions: This study provides evidence that the prevalence of polypharmacy in the elderly in Emilia-Romagna is substantial. Educational programmes should be developed to inform clinicians about the magnitude of the polypharmacy phenomenon and the patient characteristics associated with polypharmacy. Raising physicians’ awareness of polypharmacy may help to ensure safe, effective and appropriate use of medication in the elderly. Introduction Polypharmacy, the simultaneous taking of many medications, has been well documented in the US and Europe. [1-3] It is a topic of much concern for those looking to improve the quality of care for the elderly, as patients in this population often develop complicated and multi-factorial health states. As the incidence of chronic disease increases, so does the need for pharmacotherapy. [2,4] This inherently places the elderly at risk of exposure to polypharmacy. Polypharmacy in the elderly has been correlated with increased age, [2,5] and with specific diseases, including cardiovascular diseases, rheumatic diseases and respiratory illnesses. [6] Previous studies have also demonstrated that as the number of concomitant medications increases in elderly patients, so does the risk of adverse drug events. [7-9] Furthermore, polypharmacy has been found to be associated with risk of emergency department visits, hospitalizations, hospital readmissions and death in the elderly. [7,10,11] The risk of morbidity and mortality associated with polypharmacy, combined with the trend of population aging worldwide, makes polypharmacy an area of prime concern and a potential target for decreasing preventable adverse events. Despite being a well recognized problem in the elderly population, a universally accepted, formal definition for polypharmacy has yet to be established. [1,12] Several studies have categorized polypharmacy into different levels based on the number of medications taken. [1,2,13-15] More specific definitions quantify polypharmacy by the number of simultaneous medications taken by a patient. The definition that is most frequently used is the simultaneous use of five or more medications. Based on this definition, prevalence estimates for polypharmacy in the outpatient setting vary from 4% to 42% in the elderly population. [3-6,16-23] While polypharmacy in the elderly has been described in several European countries, the literature on the topic in Italy is scant. The availability of a large, linkable outpatient pharmacy database in Emilia-Romagna, Italy, a large northern region with a population of about 4 million inhabitants, provides an excellent opportunity to evaluate the prevalence of polypharmacy in the elderly and to determine patient characteristics that are predictive of exposure. Methods The study protocol was approved by the Institution Review Board of Thomas Jefferson University, Philadelphia, Pennsylvania, USA. Study Design and Population We conducted a retrospective cohort study of medication use in the elderly using the Emilia-Romagna outpatient prescriptions database from January 1, 2007 to December 31, 2007. This database includes all medications reimbursed by the 2007 National Pharmaceutical Formulary (PFN, Prontuario Farmaceutico Nazionale). 1 The characteristics of the database have been described elsewhere. [24] We linked prescription claims in the pharmacy database with data from a 2007 demographic file of 960 359 elderly Emilia-Romagna residents 1 The PFN includes all medications marketed in Italy. It has a positive and a negative drug list, outlining which medicines will be reimbursed and which need to be paid for in full by patients, respectively. All essential medications, such as cardiovascular and antihyperglycaemic drugs, are reimbursed by the PFN; nonessential medications such as benzodiazepines, as well as any over-the-counter medications such as antitussive and cold drugs, are not reimbursed. All Italian citizens are entitled to access essential healthcare services, including PFNreimbursed medications. (aged ≥65 years as at January 1, 2007). 2 The study cohort was comprised of 887 165 elderly subjects who had at least one prescription filled during the study year (92.3% of the Emilia-Romagna elderly population). Study Definitions and Measures For the purposes of this study we defined polypharmacy as the simultaneous use of five or more medications, a definition that has been widely used in previous studies. [3,13,18,19,23,25] Medications were classified using the Anatomical Therapeutic Chemical (ATC) classification index, and were further differentiated to the fifth level of classification (e.g. B01AA03 represents warfarin). [26] Duration of therapy was calculated assuming that daily drug intake was equal to the defined daily dose (DDD), as determined by the WHO. [26] In addition, it was assumed that subjects completed the duration of therapy for all filled prescriptions. Treatment was assumed to have begun on the day that the prescription was filled. The number of drugs taken on each day of the year was then calculated for each subject, and occurrence of polypharmacy was tabulated from this information. One-year prevalence was defined as the number of individuals who had at least one episode of polypharmacy during the study period. Subjects exposed to polypharmacy were also stratified by the total number of days of exposure. Incidence of polypharmacy was determined using a method previously described by Bjerrum et al. [13] Subjects with first-time polypharmacy occurrence were identified for each month. As such, elderly exposed to polypharmacy for the first time in the final 3 months of 2007 were assumed to represent true incident cases. The mean monthly first-time occurrence during the final 3 months of 2007 was assumed to represent the monthly incidence of polypharmacy. Subject Characteristics Information on subjects’ age, sex and geographic location was retrieved from the demographic file. Level of co-morbid disease was calculated using the Chronic Condition Drug Group (CCDG) score. The CCDG score classifies up to 31 chronic conditions based on consumption of specific medications. [27] The CCDG score for an individual reflects the extent to which a person is affected by 2 Because of the reimbursement process, information in the Emilia-Romagna pharmacy database is very accurate. The pharmacy database includes a unique, anonymous patient identification number, which has been used to link the pharmacy database with the demographic file. The linkage between the demographic file and the pharmacy database was virtually complete. chronic conditions (i.e. higher CCDG scores reflect a higher number of chronic conditions). Data Analysis The unit of analysis for the study was the individual subject. Descriptive statistics were generated for all variables of interest. A bivariate analysis was used to compare the characteristics of drug users exposed to polypharmacy and those not exposed using chi-squared (χ 2 ) tests for categorical variables. A multivariable logistic regression analysis was used to identify factors that were predictive of polypharmacy exposure. Subject characteristics that were incorporated in our model as independent variables included sex (dichotomously), age (categorically) and geographic location (categorically). The CCDG score was not included in our model because in a separate analysis it was shown to be correlated with the number of medications a subject received (r = 0.71), and hence inherently correlated with polypharmacy. A p-value <0.05 was considered significant for all analyses. All data analysis was completed using SAS ® version 9.1 (SAS Institute Inc., Cary, NC, USA). Results Subject Characteristics and Medication Use Of the 887 165 elderly drug users in the region, the mean ± SD age of the study population was 75.5 ± 7.5 years. Fema