Date Published: February 3, 2016
Publisher: Public Library of Science
Author(s): Heinz G. Endres, Petra Kaufmann-Kolle, Valerie Steeb, Erik Bauer, Caroline Böttner, Petra Thürmann, Angelo Scuteri.
The safety of potentially inappropriate medications (PIMs) in elderly patients is still debated. Using the PRISCUS list, we examined the incident all-cause hospitalization risk associated with PIMs compared to PIM alternatives during the 180 days post individual first pharmacy dispensing (index date).
Routine claims data from a German health insurer on 392,337 ambulatory patients aged ≥65 years, were used to estimate adjusted hazard ratios (HRs) for hospitalization associated with incident PIM use. Observation period was January 2009 –December 2010. Users of PIM alternatives, as defined by the PRISCUS list, were the reference group. Patients with PIM dispensing or hospital stay in a six month “washout” period (second half of 2008) were excluded. All potential confounders were determined in the half year before the individual index date.
In the total cohort 60.7% were female. Median age was 73 years. Of 79,041 incident PIM users, 58.4% had PIMs dispensed in one quarter of 2009 or 2010, 19.3% in two quarters, and 22.3% in three or more quarters. There were 126,535 hospitalizations during the observation period, and 47,470 of them occurred within 180 days post first dispensing. Multivariable Cox regression analysis revealed PIM use as a significant risk factor for hospitalization (HR 1.378; 95% CI 1.349–1.407) compared to use of PIM alternatives.
PIM use compared to use of PIM alternatives is associated with an increased risk of all-cause hospitalization in the 180 days following individual index date. Future analyses comparing a single PIM with its corresponding alternative may help identify those PIMs responsible for this.
Pharmacotherapy in adults 65 years of age or older is different from such treatment in younger patients. Comorbidities, multiple comedications, potential interactions, patient preferences, and physiologic decline in all steps of pharmacokinetics (PK) and pharmacodynamics (PD) must be considered. The geriatric dosing axiom, “start low and go slow” is based upon this PK/PD concern given that age-related changes in PK/PD alter the risk-benefit ratio of drug treatment . Thus, older patients are at higher risk for potentially inappropriate medication and/or dosing, which may be compounded by their need for extensive pharmacotherapy of multiple chronic conditions [2, 3]. Several explicit lists of potentially inappropriate medications (PIMs) have been introduced to assist clinicians in screening for PIMs, starting with the 1991 Beers list for nursing home residents in the USA, subsequently expanded and revised in 1997, 2003, and 2012 in order to update evidence and to improve clinical relevance [2, 4–8]. Another recently published PIM list is the German PRISCUS list, which is specifically adapted for the requirements of the German drug market. As with the Beers list, PIMs for the PRISCUS list were identified and categorized by an interdisciplinary expert panel with the Delphi method used as the consensus process . The PRISCUS list provides information regarding drugs to avoid, to be used with caution under certain circumstances, therapeutic alternatives, special comorbidities to consider, and monitoring advice if a PIM must be used. Most recently, a PIM list for several European countries was published .
We conducted a prospective cohort study based on routine data of practitioners of all medical specialties using claims data from AOK Baden-Württemberg. We deliberately chose the observation period January 2009 to December 2010 in order to avoid any influence on prescriptions by the publication of the PRISCUS list (in the second half of 2010). As an appropriate control group for patients exposed to a PIM (cases) we chose patients who received a medication classified as a safer PIM alternative in the PRISCUS list . PIM alternatives belong to the same drug class or subclass used to treat the same conditions as treated by the PIMs. Since the data provides the quantity of active ingredient(s) per pill, we were able to detect dose-dependent PIM drugs, i.e. drugs that are only characterized as PIMs above a minimum dosage (e.g. Lorazepam > 2 mg/d).
The final dataset was a cohort of 392,337 elderly patients, with a total number of 92,243 incident PIM users (23.5% of the cohort). Two-thirds of the PIM users (61,424) were women. For regression analysis the exposed group included 79,041 incident PIM users because the other 13,202 PIM cases had a hospitalization within the 180 days preceding the index date. Hence, the final control group included 313,296 incident users of a PIM alternative according to the PRISCUS list (Fig 1) .
Our results suggest that PIM use among the elderly is widespread and is associated with an increased risk of all-cause hospitalization as compared to PIM alternatives. From nearly 400,000 patients aged 65 years or older in ambulatory care of medical specialists, it was found that 23.5% received pharmacy dispensings of PIMs. Usually, the patients received PIMs for one to two quarters of the year. Thus, PIMs are still taken, at least temporarily, by approximately one-fifth of all elderly patients in ambulatory care. This is consistent with findings from prior studies [18, 24].
We compared the safety of PIMs with PIM alternatives, as defined in the PRISCUS list, in a cohort of 392,337 members of a German insurance group who were aged 65 years or older. The clinically relevant adverse event used in the comparison was hospitalization within 180 days following index date. This comparison would likely never be made in the setting of a randomized controlled trial. We adjusted for all available relevant baseline characteristics. HR calculation demonstrated a significant association between PIM dispensing and subsequent excess hospitalization. The population attributable risk percent for PIM users reached almost 6% and, assuming causality, demonstrates the need for monitoring older patients taking PIMs. As a next step, a more specific analysis comparing a single PIM or PIM drug class with the corresponding alternatives could provide a better understanding of the factors that may contribute to the increased hospitalization risk.