Use of potentially inappropriate medication and polypharmacy in elderly: a repeated cross-sectional study

Potential inappropriate medications (PIM) have an increased risk for adverse drug reactions (ADR) in an elderly population. With increasing age, multimorbidity is growing along with the use of medications. For several years, polypharmacy has been found to increase in western societies. Polypharmacy is associated with an increased risk of ADR. In this study, we analysed the prevalence of PIM in an elderly population and in different strata of the variables age, gender, number of chronic conditions and polypharmacy and how that prevalence changed over time. Methods


Introduction
One of the most common treatments, especially in elderly patients (≥75 years), are drug therapies. The goal of drug therapy is to prevent, treat or cure disease or symptoms of disease. For elderly people with multimorbidity and polypharmacy, the effect may, however, be the contrary. Advances in drug development in recent decades have resulted in that the health care system today can prevent, treat and cure more symptoms and diseases than ever before. The developments in medical practice and drug development have significantly contributed to the increase in life expectancy that is seen today [ 1 ].
With longer life expectancy and higher multimorbidity, the risk of polypharmacy increases.
Polypharmacy, most commonly defined as the use of five or more medications at the same time, increases the risk of interactions or side effects from drug therapy [ 2 , 3 ]. Adverse drug reactions (ADR) from interactions or side effects can be misinterpreted as new symptoms or diagnoses and generate prescriptions for new medications. This negative spiral of prescribing to treat side effects or interactions is also known as the prescribing cascade and increases the risk of polypharmacy. Except for drug-drug interactions that can increase the risk of the prescribing cascade, drugdiagnose interaction or contraindication can lead to an increased risk [ 4 , 5 ]. With use of multiple medications and the presence of multiple chronic conditions in a patient, the risk of medications that are contraindicated for one of the chronic conditions increases. Side-effects, drug-drug and drug-diagnose interactions all increase the risk of adverse drug events (ADE) [ 6 ] The risk of side effects and ADR also increases with physiological age, which is related to changes that occur in the body as we age, for example, altered body fat/water ratio and decreased kidney function. As a result of these changes, the pharmacokinetic and pharmacodynamic properties of medications can be changed. The elderly population therefore has a higher risk of side effects and adverse reactions from e.g. medications that are lipophilic or have a high renal elimination compared to a younger and middleaged population [ 1 , 6 ]. These medications with a higher risk for side effects are commonly referred to by the term potentially inappropriate medications (PIM) for elderly. The definition of PIM for elderly varies between different quality criteria mainly because they are developed in different countries with different treatment regimens [ 7 ]. The two frequently used quality criteria are Beers and the Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) criteria [ 8 , 9 ]. In Sweden, the Swedish National Board of Health and Welfare has published a Swedish version in the report; 'Quality indicators for good drug therapy in elderly'. The indicators cover a range of different quality indicators for drug treatment in elderly [ 10 ]. The purpose of the indicators is to facilitate the follow-up of medical treatment in an elderly population. Use of potentially inappropriate medication (PIM) in the elderly has been found to lead to increased morbidity and mortality [ 10 , 11 ]. From 2010 to 2014, there was a national campaign to improve care of elderly in Sweden [ 12 ]. Among many strategies, there was a focus on reducing use of PIM in elderly 75 years and older.
The aim of this descriptive study was to analyse the prevalence of PIM in an elderly population and in different strata of the variables age, gender, number of chronic conditions and polypharmacy and how that prevalence changed over time.

Setting and study populations
Blekinge is located in the southeastern corner of Sweden and is one of the smallest counties with approximately 153 000 inhabitants in 2011 and 2013. Almost all inhabitants are registered to a primary care center in Sweden. The majority of funding for primary health care comes from a specific county council tax, both public (operated by the county council) and private care centers. Both public and private primary care centers were included in the study. We included two cohorts for comparison in this registry based In Sweden, prescribed medicines are prescribed for use at most three months within the high cost threshold for medicines. Therefore a three month period was used to construct a medicine list on both regularly used and as-needed medicines [ 15 ]. If the same drug was dispensed more than once it was still counted only once.
Since the county council's register of dispensed medicines does not contain exact dose, we used Defined Daily Doses (DDD) to calculate the duration of the drug exposure. We Multimorbidity was defined as number of chronic conditions. It was determined by using a validated assessment tool that captures chronic conditions grouped in 60 different diagnose categories [ 17 ]. All information about diagnoses for a two-year period prior to 31/3-2011 (cohort 1) and 31/12-2013 (cohort 2) were included.

Data analyses
All variables were used as categories in the analyses. Gender was categorised as male or female and use of PIM; use or no use of PIM. Age was categorised into four groups: 75-<80, 80-<85, 85-<90 and ≥90 and number of chronic conditions was divided into five groups or strata: none, one, two to four, five to seven and eight or more, chronic conditions. For the descriptive analysis of the cohorts, use of medications were divided into three strata; no-medication, use of 1 to 4 and use of five or more. A first descriptive analysis of the two cohorts in the different strata of the variables age, gender, use of PIM, number of chronic conditions and polypharmacy was performed. The differences were analysed using chi-square test. A significance level (α) of 0.05 and 0.001 was used.
Polypharmacy is known to increase the risk of ADR and therefore we wanted to analyse polypharmacy in the different strata [ 3 ]. For analysis of polypharmacy in different strata, use of medication was divided into two categories; no use to use of four medications (<5, no-polypharmacy) and use of five or more (≥5, polypharmacy). Nonusers of medications decreased from 20.82% to 19.19%, the use of 1-4 medications increased from 46.57% to 47.39% and the prevalence of polypharmacy from 32.62% to 33.41% (p-value <0.001) ( Table 1).
Use of PIM decreased in all strata of the variables. Among patients with chronic conditions, the greatest decrease was seen in two to four chronic conditions from 4.28% to 2.75% (p-value, <0.001) (  24 ]. Therefore, quality indicators that aim to decrease the use of PIM can lead to an improvement of quality in drug treatment in elderly.
In our study, the prevalence of multimorbidity increased but the prevalence of polypharmacy stayed relatively stable. That polypharmacy stabilises while the number of chronic conditions increases is an interesting finding. One could think that if multimorbidity is increasing that polypharmacy would hence follow. However, the use of medication did increase; just not polypharmacy in comparison with the rest of the population.
As a result of medical developments in recent decades, more morbidities are treatable which has led to increased use of number of medications [ 1 ]. Number of drugs, as polypharmacy, are frequently used and also found to be an independent risk factor for ADRs while very few studies include a morbidity measurement when evaluating quality of drug treatment [ 25 , 26 ]. Polypharmacy increases the risk of drug-drug interaction considerably [ 4 ]. Use of medication has been found to increase with age even after adjustment of level of multimorbidity [ 27 ]. One could argue that the severity of the morbidity is increasing with age and therefore the number of medications increases. Nonetheless, polypharmacy is not wrong, per se, as long as the complete medication list is reviewed, and the risk benefit ratio is considered for the individual patient; this is called appropriate polypharmacy [ 1 , 28 ]. When evaluating quality of drug treatment in elderly and the risk of ADE, it is sometimes difficult to include and to evaluate contraindications for drug use, drugdiagnose interactions that lead to ADEs. This increases the risk of underestimating the risk of ADEs when evaluating risk of drug use in studies.
Our result shows that even if the use of PIM decreases, the prevalence of polypharmacy is stable while the number of chronic conditions increases. The most common drug classes in patients 75 years and older with polypharmacy are not PIM (according to our definition) but cardiovascular drugs (including antithrombotic agents), analgesics and psychotropic drugs [ 29 ]. These are also the most commonly used drugs in drug-related events such as bleeding or bruising, which are associated with antithrombotic agents and dizziness or unsteadiness due to psychotropic medicines [ 6 ]. Different methods have been tested to improve drug treatment in elderly.
Implementing the STOPP criteria in a hospital setting reduced the number of ADR in a study from Cork University Hospital [ However, it still demonstrates that improvement of quality of care can be achieved through implementing different systematic methods for optimisation of drug treatment in elderly. There are several studies that show that using a systematic method, such as medication reviews, in multi professional teams reduces the use of PIM and medication cost. It is a method developed not to focus on specific risk medication but a systematic approach to optimise a patient's medical treatment as a whole; diagnoses, medicines and patient's physical conditions, e.g. kidney function [ 31-33 ].

Strengths and Limitations
Our definition from the Swedish National Board of Health and Welfare is stricter in its definition and includes fewer drugs and drug classes than other definitions [ 7 , 10 ]. For example, we do not include nonsteroidal anti-inflammatory drug (NSAID) or cardiovascular drugs except for disopyramide. Our definition of PIM is commonly used in Sweden as an indicator for quality of drug treatment in elderly, both nationally and by county councils, and is therefore relevant in this setting. This means that our results cannot be directly translated to other settings where the definition of PIM is broader.
The information of medicines in the study was register data from the county council's register that includes prescribed and pharmacy dispensed medicines for all inhabitants in Blekinge. We were not able to assess use of illegal drugs or over the counter drugs in this study. Data from the Medical Products Agency indicates that 11% of the Swedish population bought prescription drugs from non-approved pharmacies during 2011 [ 34 ]. By constructing a medicine list on collected prescribed drugs from the index date of hospitalisation and three months back for each risk set, it allowed us to determine, as closely as possible, as to what the patient was using. On the other hand, there is a possibility that we are missing medications used as needed because they are dispensed more rarely than every three months. We were also unable to take compliance into consideration when determining use of PIM.
Multimorbidity in the study population was measured as the number of chronic conditions and is dependent on the quality of registration of diagnoses [ 17 ]. The recording of diagnoses in this study has not been validated. However, we used registered diagnoses from a two-year period from both primary-and secondary care to get as close to total coverage as possible. Another Swedish study has found that 75% of the total population in Blekinge county had at least one diagnosis registered during a Due to the requirement of anonymized data, each individual could not be asked for consent to participate; active refusal of participation was instead applied. This was done by publishing information about the planned study in the Swedish local newspapers "Sydöstran" and "Blekinge Läns Tidning". The advertisement presented the study and contained information on how to contact the data extractor in Blekinge county council by phone, email or mail in order to opt out of the study. The data extractor was then responsible for that those who opted out were excluded before any data were delivered to the research manager, Kristine Thorell.

Consent for publication Not applicable
Availability of data and material The datasets generated and/or analysed during the current study are not publicly available due to individual privacy being compromised.