The prevalence of polypharmacy in elderly: a cross section study from Bosnia and Herzegovina

Kosana D. Stanetić1, Suzana M. Savić1, Bojan M. Stanetić2, Olja M. Šiljegović3, Bojana S. Đajić4 1Primary Health Center Banja Luka, Department of family medicine, Medical faculty, University of Banja Luka, Bosnia and Herzegovina 2Department of Cardiology, University Clinical Center of the Republic of Srspka, Banja Luka, Bosnia and Herzegovina 3Primary Health Center Doboj, Bosnia and Herzegovina 4Primary Health Center Gradiška, Bosnia and Herzegovina The prevalence of polypharmacy in elderly: a cross section study from Bosnia and Herzegovina Оригинални радови / Original Articles


Introduction
We define polypharmacy as a simultaneous usage of five or more drugs, an over usage of medically indicated drugs, or a therapy regime in which at least one type of drug is unnecessary 1 .As the human population grows older, the multi-morbidity increases and polypharmacy intensifies, all of which consequently represents a risk of new morbidity and mortality.Polypharmacy, the usage of different supplements, non-prescribed drugs, and potentially undesirable drug effects set a challenge for the efficient drug prescription.Adverse drug effects frequently cause hospitalization, and one of USA studies proved that undesirable drug effects caused 25% of hospitalizations of patients aged more than 80 2 .
Drugs play a pertinent part in treating geriatric patients for chronic diseases in order to alleviate the pain and improve quality of life 3 .It is crucial for a family doctor to rationally prescribe drugs and get well-acquainted with pharmacokinetics and pharmacodynamics of drugs in the elderly 4 .
Aging affects pharmacokinetics and pharmacodynamics of drugs, which further impacts on the choice and dosage of drugs.Drug effects with the elderly may be more or less highlighted than with the younger patients.The nervous system of the elderly is more sensitive to opioid analgesics, benzodiazepines, antipsychotics, and antiparkinsonics.As one grows older, effects of some drugs are minor (e.g.beta blockers), and there are some changes in drug absorption.The reduced absorption is caused by the decreased small intestine surface and the increased stomach pH.The drug distribution within the body is altered due to the decrease in fluids and muscles and the increase in fat tissue.Liposoluble drugs are better distributed with the elderly patients.Furthermore, aging causes changes in metabolism and drug elimination.Metabolism of many drugs is affected by the impaired flow through the liver and the reduced liver mass.The kidney mass and renal flow are reduced and creatinine clearance decreases, which further causes the reduced renal drug elimination that correlates with the creatinine clearance which drops by 50% between the age 25 and 85.Drug pharmacodynamics is closely related with changes in drug sensitivity, which may rise or fall as one ages.These changes are due to deviations in drug-receptor bonds, the decrease in number of receptors, or an altered cellular response 5,6 .
Polypharmacy represents a large burden for developed countries due to undesirable drug effects.In these countries, approximately 1 to 4 elderly patients get hospitalized because of the prescription of at least one inadequate drug, and around 20% of all hospital patient deaths are caused by potentially preventable undesirable drug effects 7 .
In order to rationally prescribe drugs, one may follow recommendations of Mark Beers, an American geriatric doctor, who defined criteria for drug prescription to elderly patients and who determined which drugs should be avoided, which should have a limited usage, and the dosage of which should be time-limited 8,9 .In practice, one may find it rather useful to use criteria singled out by an Irish scientist Gallagher and his associates, who determined which drugs were possibly inadequate for patients aged more than 65 -STOPP (Screening Tool of Older Person's Prescriptions) and criteria for drug prescription for patients aged more than 65 under the condition that there were no subscription contraindications -START (Screening Tool to Alert doctors to Right Treatment).The purpose of these criteria was to set the evidence-based rules in order to avoid the common, potentially inadequate prescriptions and possible negligence 10 .
The aim of our study was to estimate the prevalence of 65+ patients who continuously use five or more drugs and to single out the most frequently used drugs in reference with sex and age.

Method
The research was a cross section study run during October-December 2015 period.During the study, we examined electronic medical charts of all patients older than 65 who were registered at two family clinic departments at the Educational Family Medicine Centre of the Banja Luka Health Centre.The research protocol was approved by the relevant local ethics committee and complies with the Declaration of Helsinski.
Data collected from the electronic medical charts referred to age, sex, chronic diseases (cardiovascular diseases, mental illness and neurological diseases, musculoskeletal diseases, diabetes, malignant diseases, renal insufficiency, glaucoma, benign prostatic hyperplasia, and other chronic diseases) and drugs used in a continuous therapy (antihypertensive, nitrates, diuretics, antiarrhythmic, benzodiazepine, anti-epileptic, anti-parkinsonians, anticoagulation therapy, anti-aggregation therapy, nonsteroidal anti-inflammatory drugs, oral anti-diabetics, insulin, systemic corticosteroids, combination of beta 2 agonist + inhalator corticosteroids, bisphosphonates, statins, alpha1 adrenergic receptors, and other drugs used by the patients in a continuous therapy).We also surveyed the patients on supplementary drugs (ginkgo biloba, omega 3 fatty acids, herbal supplements for treating benign prostatic hyperplasia, vitamin supplements, mineral supplements, etc.) which they use either upon doctor's instructions or they buy it in chemist's self-willingly.All the data were entered into a questionnaire designed for the purpose of our study.Furthermore, data were entered into a Microsoft Excel chart and were statistically processed using SPSS program.

Examinees
The study covered 432 patients registered at two family clinic departments at the Educational Family Medicine Centre of the Banja Luka Health Centre, who were older than 65, suffered from at least one chronic disease, and used at least one drug in a continuous therapy.For the purpose of our study, the patients were singled out in reference with age.The first group were patients aged 65 to 70, the second group were patients aged 71 to 75, the third group were patients aged 76 to 80, and the fourth group were patients aged 80+.

Statistical methods
We used a descriptive analysis of frequency and percentage in order to examine the samples for patients with chronic diseases and the type of drugs they used in a continuous therapy.Chi-Square test was used in order to determine to which extent age affected the usage of most frequently prescribed continuous drugs.The non-parametric Spearman's coefficient was used where appropriate for the regression analyses.The effect of age on the number of continuous drugs with polypharmacy patients was determined by using the non-parametric Kruskal-Wallis test.

Results
In the present study, 3551 patients who were registered at two family clinic departments at the Educational Family Medicine Centre of the Banja Luka Health Centre were screened.A total number of 432 patients aged 65+ were included in this study.Out of 432 patients included, 243 (56.25%) patients continuously used fewer than five drugs as follows: 27 (6.3%)patients used one drug, 44 (10.2%) patients used two drugs, 83 (19.2%) patients used three drugs, and 89 (20.6%) patients used four drugs.On the other hand, 189 (43.75%) patients used five or more drugs as follows: 61 (14.1%) patients used five drugs, 44 (10.2%) patients used six drugs, 49 (11.3%)patients used seven drugs, 17 (3.9%)patients used eight drugs, 11 (2.5%) patients used nine drugs, and 7 (1.6%)patients used ten drugs.
There were 170 (39.35%) male patients and the average age was 73.88 ± 6.5, in which the youngest patient was 65 and the oldest one was 92 years of age.The group aged 65-70 covered 166 (38.45 %) patients, the group aged 71-75 had 101 (23.37 %), the group aged 76-80 had 86 (19.90 %), and the group aged 81+ had 79 (18.28%) patients.The most common chronic diseases were cardiovascular and musculoskeletal diseases.In addition, 94 patients suffered from diabetes type 2, and 35 patients suffered from a malignant disease (Table 1).The following were the most frequently used drugs with patients treated for cardiovascular diseases: ACE inhibitors 186 (43.1%),ACE inhibitor + diuretic combination 177 (41.0%), beta blockers 136 (31.5%), calcium channel blockers 131 (30.3%), nitrates 105 (24.3%), statins 114 (26.4%), anti-aggregation therapy (ASA, clopidogrel) 157 (36.3%), and benzodiazepine 195 (45.1%) (Table 2).We statistically processed the obtained results in order to examine the usage of individual drugs or a group of drugs in comparison with age.The analysis showed that the usage of nitrates (p = 0.000), diuretics (p = 0.005) and antiarrhythmic drugs (p = 0.014) statistically largely increased with age.Speaking of statin usage, there was a statistically relevant difference among our test groups in reference with age (p = 0.028), in which case patients aged 71-75 mostly used these drugs and patients aged 81+ used them the least (Table 3).There were 65 (34.39%)male and 124 (65.61%) female patients within the group who continuously used five or more drugs.Chi-Square test showed no statistically relevant difference (p=0.119) in number of used drugs between male and female patients.
In the regression analysis, number of drugs taken by the study population did not correlate with age (R 2 =0.022, Figure 1).Furthermore, the effect of age on the number of drugs used in a continuous therapy with polypharmacy patients could not be proved (Kruskal-Wallis, p=0.555, Figure 2).

Discussion
Results of our study have shown a high percentage of polypharmacy patients (43.75%).This phenomenon exists in most developed countries, which has been proved in multiple studies led by other authors.Hence, Golchin et al conducted a study on 59 patients aged 65+ and proved polypharmacy with 35.6% of the examinees. 11Opposite to our opinion, results of a UK study that covered 1,900 patients aged 65+ indicated that the number of polypharmacy patients grew as the time passed.Thus, 15.1% of patients used 5 to 9 drugs in 2003, and the figures rose up to 25.2% in 2011.Results of the same study showed that the number of patients using 10 or more drugs grew from 1.3% in 2003 up to 3.8% in 2011 12 .
Many authors studied the prescription of potentially inadequate drugs to the elderly and they compared their results with Beers, STOPP, and START criteria.The study of Bradley et al included 166,108 patients aged 70+ and they inferred that 34% of the patients were using potentially inadequate drugs longer than three months -NSAIDs (nonsteroidal antiinflammatory drugs) 9% and benzodiazepine 6% 13 .In addition, results of our study showed that the patients mostly used NSAIDs (12.5%) as a long-term therapy, and even 45.1 % used benzodiazepine.
A French study showed an upward trend in prescribing drugs to the elderly over the last decade, and the most commonly prescribed drugs were for cardiovascular disease treatment, analgesics, and NSAIDs 14 .Likewise, a large national research in Taiwan indicated a high level (86.2%) of prescription of potentially inadequate drugs to the elderly, of which most frequent ones were NSAIDs and benzodiazepine 15 .Drugs for cardiovascular disease treatment were also most commonly prescribed drugs in our study but there were also many patients using benzodiazepine, analgesics, and NSAIDs.
According to our study, most commonly prescribed drugs were those for cardiovascular disease treatment, which complies with the most frequent chronic diagnosis.Moreover, 45.1% of benzodiazepine continuous usage is troublesome due to its effect on the fall risk, cognitive damages, delirium, and possible car accidents.A relatively large number of patients using NSAIDs (12.5%) as a long-term therapy is a risk to gastrointestinal bleeding.
Drug prescription to the elderly patients demands a balance between too many or too few drugs.Hence, it is necessary to consider specificities typical of this age as well as the potentially undesirable drug effects.

Conclusion
Polypharmacy was present with 43.75% patients in our study.We found no statistically relevant difference for patients with polypharmacy between the number of drugs in reference with either sex or age.Mostly used potentially inadequate drugs were nonsteroidal anti-inflammatory drugs and benzodiazepines.A clinical assessment of a family doctor along with an individual treatment plan based upon medical, functional, and social conditions should be the foundation of the rational drug prescription at family clinic departments.

Kosana D. Stanetić at al.
The prevalence of polypharmacy in elderly: a cross section study from Bosnia and Herzegovina There were 65 (34.39%)male and 124 (65.61%) female patients within the group who continuously used five or more drugs.Chi-Square test showed no statistically relevant difference (p=0.119) in number of used drugs between male and female patients.In the regression analysis, number of drugs taken by the study population did not correlate with age (R 2 =0.022), (Figure 1).Furthermore, the effect of age on the number of drugs used in a continuous therapy with polypharmacy patients could not be proved (Kruskal-Wallis, p=0.555, Figure 2).

Discussion
Results of our study have shown a high percentage of polypharmacy patients (43.75%).This phenomenon exists in most developed countries, which has been proved in multiple studies led by other authors.Hence, Golchin et al conducted a study on 59 patients aged 65+ and proved polypharmacy with 35.6% of the examinees. 11Opposite to our opinion, results of a UK study that covered 1,900 patients aged 65+ indicated that the number of polypharmacy patients grew as the time passed.Thus, 15.1% of patients used 5 to 9 drugs in 2003, and the figures rose up to 25.2% in 2011.Results of the same study showed that the number of patients using 10 or more drugs grew from 1.3% in 2003 up to 3. 8% in 2011 12 .Many authors studied the prescription of potentially inadequate drugs to the elderly and they compared their results with Beers, STOPP, and START criteria.The study of Bradley et al included 166,108 patients aged 70+ and they inferred that 34% of the patients were using potentially inadequate drugs longer than three months -NSAIDs (nonsteroidal anti-inflammatory drugs) 9% and benzodiazepine 6% 13 .In addition, results of our study showed that the patients mostly used NSAIDs (12.5%) as a long-term therapy, and even 45.1 % used benzodiazepine.

Figure 1 .
Figure 1.Linear regression of age vs. number of drugs

Figure 2 .
Figure 2. The effect of age on the number of drugs used in a continious therapy with polypharmacy patients (n=189) Kosana D. Stanetić at al.The prevalence of polypharmacy in elderly: a cross section study from Bosnia and Herzegovina

Table 1 .
Chronic diseases of the patients (n=432)

Table 2 .
Drugs used within a continuous therapy (n=432)

Table 3 .
Effect of age on the usage of most commonly prescribed drugs in continuous therapy (n=432) *Statistically relevant difference at p<0,05