Archives of Gerontology and Geriatrics 59 (2014) 630–635
Contents lists available at ScienceDirect
Archives of Gerontology and Geriatrics journal homepage: www.elsevier.com/locate/archger
Potentially inappropriate medications (PIMs) and anticholinergic levels in the elderly: A population based study in a French region Jean-Baptiste Beuscart a,b,*, Corinne Dupont c, Marie-Margueritte Defebvre c, Francois Puisieux a a b c
Geriatric Department, University Hospital of Lille, France Department of Biostatistics, EA2694, University Lille 2, Lille, France Agence Re´gionale de Sante´ Nord-Pas-de-Calais, Lille, France
A R T I C L E I N F O
A B S T R A C T
Article history: Received 3 April 2014 Received in revised form 6 August 2014 Accepted 8 August 2014 Available online 19 August 2014
Prescriptions of PIMs and anticholinergic drugs lead to adverse events and hospitalizations in the elderly. The objective of this study was to determine the prevalence of PIMs and prescriptions with a high anticholinergic effect in a French region. All prescriptions dispensed at community pharmacies in patients aged 75 and older between January 1 and March 31, 2012 were extracted from French Health Insurance information System – Nord-Pas-de-Calais Region for patients affiliated to the Social Security. Prescription of PIMs was defined according to the Laroche list. The anticholinergic score for each prescription was calculated using the Anticholinergic Drug Scale (ADS). 65.6% (n = 207,979) of people aged over 75 years, living in the Nord-Pas-de-Calais Region were included, of which 4.5% (n = 9284) living in nursing homes. Patients received an average of 8.3 drugs over the 3-month study period. In 32.6% (n = 67,863) of patients, at least one PMI was prescribed. According to the ADS, 10.0% (n = 20,978) of patients in the general population and 24.0% (n = 2231) of patients living in nursing homes was exposed to a prescription with a high or very high anticholinergic score (ADS 3). Hydroxyzine prescribed in 51.4% (n = 10,792) of them ranked first among drugs most often reported. In conclusion, PMIs and anticholinergic drugs were commonly prescribed in elderly living in the Nord-Pas-de-Calais Region. Improving the quality of prescriptions in the elderly appears necessary. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Inappropriate prescription Cholinergic antagonists Elderly Pharmacoepidemiology
1. Introduction In recent years, the number of prescribed drugs per patient has risen progressively all over the world and in France, and elderly people are major consumers (Gallagher, Barry, & O’Mahony, 2007; Haider, Johnell, Thorslund, & Fastbom, 2007; Hovstadius, Hovstadius, Astrand, & Petersson, 2010). The main reasons for this evolution are a longer life expectancy and an associated increase in chronic disease prevalence (Marengoni, Rizzuto, Wang, Winblad, & Fratiglioni, 2009). Many studies have shown that suboptimal or inappropriate prescribing is highly prevalent in the elderly leading to an increased risk of adverse drug events (ADEs), morbidity, mortality, and healthcare utilization (Hamilton, Gallagher, &
* Corresponding author at: CERIM, EA 2694, Faculte´ de Me´decine – Poˆle Recherche, 1, place Verdun, F – 59045 Lille Cedex, France. Tel.: +33 6 31 59 2866; fax: +33 3 2062 6881. E-mail address: [email protected] (J.-B. Beuscart). http://dx.doi.org/10.1016/j.archger.2014.08.006 0167-4943/ß 2014 Elsevier Ireland Ltd. All rights reserved.
O’Mahony, 2009). Inappropriate prescribing includes the use of PIMs, the misuse of medications (dose or duration), the use of medications with potentially serious drug–drug or drug–disease interactions, the overuse or underuse of medications. PIMs are defined as drugs with risk of ADEs exceeding their expected clinical benefit in patients, particularly when safer therapeutic alternatives are available to treat the same condition (Matanovic´ & VlahovicPalcevski, 2012). Several sets of explicit criteria for PIMs have been developed in the elderly. The Beers criteria are the most widely used in the scientific literacy but these North American criteria may not be relevant for Europe (Beers, 1997). Availability of drugs, clinical practice, socioeconomic levels and health care systems in Europe differ from those prevailing in the United States. The Laroche list has recently been proposed to detect PIMs in France and Europe (Laroche, Charmes, & Merle, 2007). The prevalence of PIMs was estimated at 53.6% by using this list in a large representative sample of French elderly people (Bongue et al., 2011). The French authorities have led health policy inciting to reduce PIM’s prescription, notably
J.-B. Beuscart et al. / Archives of Gerontology and Geriatrics 59 (2014) 630–635
cerebral vasodilators. However, its impact has not been evaluated in a large population-based study of elderly people in France. Drugs with anticholinergic effects are often specifically identified in lists of PIMs (Beers, 1997; Laroche et al., 2007). It is well known that the use of anticholinergic drugs is associated with increased risk of falls, cognitive impairment, delirium, and increased mortality (Ancelin et al., 2006; Huang, Chan, Shih, & Lee, 2012; Lampela et al., 2013; Landi et al., 2007). However, these lists do not take into account the fact that cumulative exposure of drugs with weak anticholinergic effects or with strong anticholinergic effects may be significant. Thus some scores have been developed based on known clinical effects and serum anticholinergic activities. The ADS was proposed to determine the potential anticholinergic of a prescription (Carnahan, Lund, Perry, Pollock, & Gulp, 2006; Dura´n, Azermai, & Stichele, 2013). The issue of the risk associated of anticholinergic effect is of particular concern in elderly, but remains poorly known for physicians. Additionally, the prevalence of prescriptions with a high anticholinergic effect in the general population is not known. The objective of this study was to determine the prevalence of PIMs and prescriptions with a high anticholinergic effect in a large population of people aged 75 and over living in a French region.
2. Patients and methods 2.1. Study design and source of data We conducted an observational study using the reimbursed prescriptions in non-hospital pharmacies between January 1 and March 31, 2012 in the French Nord-Pas-de-Calais Region. The number of people aged 75 and over living in the Nord-Pas-deCalais Region was estimated to 303,577 people for a total population of 4,035,269 inhabitants in 2010 (from INSEE, the French National Institute for Statistics and Economic Studies). All prescriptions of patients affiliated to the compulsory general scheme of Social Security System were retrieved from the French Health Insurance Information System of the Nord-Pas-de-Calais Region. This scheme covers 65.9% of people aged 75 and over in the Nord-Pas-de-Calais Region. Prescriptions for the elderly living in nursing homes with a pharmacy division and those affiliated to another health insurance system were not collected in this study. A total of 209,411 people aged 75 and over were eligible for the study. People who did not have any reimbursed prescription during the study (n = 255; 0.1%) or any prescription with at least one oral or injectable drug (n = 1177; 0.6%) were excluded from the study. Finally, the analysis focused on reimbursed prescriptions for 207,979 people aged 75 and over during the 3-month study period. 2.2. Data collection
631
PIM: medications were classified as inappropriate according to the list of Laroche (Laroche et al., 2007). This list is comprised of 34 criteria divided into three groups: (1) drugs with an unfavorable benefit to risk ratio, (2) drugs with questionable efficacy, and (3) drugs with both an unfavorable benefit to risk ratio and a questionable efficacy. Criteria involving a particular clinical situation (criteria 21–25) and those based on the dose (criteria 14, 27) were not considered, as the database did not contain these data. Anticholinergic score of prescriptions: The anticholinergic effect of prescriptions was measured using the ADS adapted according to the recent study of Dura´n et al. (2013). In this scale, the drugs were rated in an ordinal manner from zero to three. The zero level was assigned to an absence of known anticholinergic activity and level three to a high anticholinergic activity. The anticholinergic score of a given prescription was obtained by summing up levels of all prescribed drugs. This score was calculated for each prescription. For a given patient, only the prescription with the highest anticholinergic score was retained for the analysis. 2.4. Statistical analysis Quantitative variables were described by mean and standard deviation (SD) if the normality hypotheses (Shapiro–Wilks test) were fulfilled and by median and first and third quartiles (Q1, Q3) otherwise. Qualitative variables were described by frequency and percentage. Correlation between variables was performed using the Spearman’s rank test. 3. Results 3.1. Patients January 1 and March 31, 2012, a total of 207,979 people aged 75 years and over had at least one reimbursed prescription containing an oral or injected drug. They represented 99.3% of eligible people and 65.6% of people aged 75 years and over living in the Nord-Pas-de-Calais region. The majority of patients lived in their own home. Patient characteristics are shown in Table 1. 3.2. Polypharmacy is related to the total number of prescriptions per patient rather than the total number of drugs per prescription There was an important difference between the total number of drugs per prescription and the total number of drugs per patient. This result is shown in Fig. 1. The number of drugs per prescription was often relatively low with only one to four drugs prescribed in Table 1 Characteristics of the study population. Patients (n = 207,979)
All prescriptions issued and reimbursed in community pharmacy were extracted over the study period. All data were anonymous. Each prescription was characterized by a patient identifier (anonymous number), the prescribed drugs, the prescriber (anonymous number), the pharmacist who issued the prescription (anonymous number), the dates of prescription and drug delivery. Patient characteristics included age, gender, living at home or in nursing homes. 2.3. Classification of drugs Drugs were coded according to the Anatomical Therapeutic Chemical (ATC) Classification System. Oral or injectable medications were recorded. Eye drops, ointments, and aerosols were excluded from this study.
Age [years; mean (S.D.)] Female Living in nursing home Number of prescriptions during the 3-month study period [median IQR] Number of drugs during the 3-month study period
Contents lists available at ScienceDirect
Archives of Gerontology and Geriatrics journal homepage: www.elsevier.com/locate/archger
Potentially inappropriate medications (PIMs) and anticholinergic levels in the elderly: A population based study in a French region Jean-Baptiste Beuscart a,b,*, Corinne Dupont c, Marie-Margueritte Defebvre c, Francois Puisieux a a b c
Geriatric Department, University Hospital of Lille, France Department of Biostatistics, EA2694, University Lille 2, Lille, France Agence Re´gionale de Sante´ Nord-Pas-de-Calais, Lille, France
A R T I C L E I N F O
A B S T R A C T
Article history: Received 3 April 2014 Received in revised form 6 August 2014 Accepted 8 August 2014 Available online 19 August 2014
Prescriptions of PIMs and anticholinergic drugs lead to adverse events and hospitalizations in the elderly. The objective of this study was to determine the prevalence of PIMs and prescriptions with a high anticholinergic effect in a French region. All prescriptions dispensed at community pharmacies in patients aged 75 and older between January 1 and March 31, 2012 were extracted from French Health Insurance information System – Nord-Pas-de-Calais Region for patients affiliated to the Social Security. Prescription of PIMs was defined according to the Laroche list. The anticholinergic score for each prescription was calculated using the Anticholinergic Drug Scale (ADS). 65.6% (n = 207,979) of people aged over 75 years, living in the Nord-Pas-de-Calais Region were included, of which 4.5% (n = 9284) living in nursing homes. Patients received an average of 8.3 drugs over the 3-month study period. In 32.6% (n = 67,863) of patients, at least one PMI was prescribed. According to the ADS, 10.0% (n = 20,978) of patients in the general population and 24.0% (n = 2231) of patients living in nursing homes was exposed to a prescription with a high or very high anticholinergic score (ADS 3). Hydroxyzine prescribed in 51.4% (n = 10,792) of them ranked first among drugs most often reported. In conclusion, PMIs and anticholinergic drugs were commonly prescribed in elderly living in the Nord-Pas-de-Calais Region. Improving the quality of prescriptions in the elderly appears necessary. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Inappropriate prescription Cholinergic antagonists Elderly Pharmacoepidemiology
1. Introduction In recent years, the number of prescribed drugs per patient has risen progressively all over the world and in France, and elderly people are major consumers (Gallagher, Barry, & O’Mahony, 2007; Haider, Johnell, Thorslund, & Fastbom, 2007; Hovstadius, Hovstadius, Astrand, & Petersson, 2010). The main reasons for this evolution are a longer life expectancy and an associated increase in chronic disease prevalence (Marengoni, Rizzuto, Wang, Winblad, & Fratiglioni, 2009). Many studies have shown that suboptimal or inappropriate prescribing is highly prevalent in the elderly leading to an increased risk of adverse drug events (ADEs), morbidity, mortality, and healthcare utilization (Hamilton, Gallagher, &
* Corresponding author at: CERIM, EA 2694, Faculte´ de Me´decine – Poˆle Recherche, 1, place Verdun, F – 59045 Lille Cedex, France. Tel.: +33 6 31 59 2866; fax: +33 3 2062 6881. E-mail address: [email protected] (J.-B. Beuscart). http://dx.doi.org/10.1016/j.archger.2014.08.006 0167-4943/ß 2014 Elsevier Ireland Ltd. All rights reserved.
O’Mahony, 2009). Inappropriate prescribing includes the use of PIMs, the misuse of medications (dose or duration), the use of medications with potentially serious drug–drug or drug–disease interactions, the overuse or underuse of medications. PIMs are defined as drugs with risk of ADEs exceeding their expected clinical benefit in patients, particularly when safer therapeutic alternatives are available to treat the same condition (Matanovic´ & VlahovicPalcevski, 2012). Several sets of explicit criteria for PIMs have been developed in the elderly. The Beers criteria are the most widely used in the scientific literacy but these North American criteria may not be relevant for Europe (Beers, 1997). Availability of drugs, clinical practice, socioeconomic levels and health care systems in Europe differ from those prevailing in the United States. The Laroche list has recently been proposed to detect PIMs in France and Europe (Laroche, Charmes, & Merle, 2007). The prevalence of PIMs was estimated at 53.6% by using this list in a large representative sample of French elderly people (Bongue et al., 2011). The French authorities have led health policy inciting to reduce PIM’s prescription, notably
J.-B. Beuscart et al. / Archives of Gerontology and Geriatrics 59 (2014) 630–635
cerebral vasodilators. However, its impact has not been evaluated in a large population-based study of elderly people in France. Drugs with anticholinergic effects are often specifically identified in lists of PIMs (Beers, 1997; Laroche et al., 2007). It is well known that the use of anticholinergic drugs is associated with increased risk of falls, cognitive impairment, delirium, and increased mortality (Ancelin et al., 2006; Huang, Chan, Shih, & Lee, 2012; Lampela et al., 2013; Landi et al., 2007). However, these lists do not take into account the fact that cumulative exposure of drugs with weak anticholinergic effects or with strong anticholinergic effects may be significant. Thus some scores have been developed based on known clinical effects and serum anticholinergic activities. The ADS was proposed to determine the potential anticholinergic of a prescription (Carnahan, Lund, Perry, Pollock, & Gulp, 2006; Dura´n, Azermai, & Stichele, 2013). The issue of the risk associated of anticholinergic effect is of particular concern in elderly, but remains poorly known for physicians. Additionally, the prevalence of prescriptions with a high anticholinergic effect in the general population is not known. The objective of this study was to determine the prevalence of PIMs and prescriptions with a high anticholinergic effect in a large population of people aged 75 and over living in a French region.
2. Patients and methods 2.1. Study design and source of data We conducted an observational study using the reimbursed prescriptions in non-hospital pharmacies between January 1 and March 31, 2012 in the French Nord-Pas-de-Calais Region. The number of people aged 75 and over living in the Nord-Pas-deCalais Region was estimated to 303,577 people for a total population of 4,035,269 inhabitants in 2010 (from INSEE, the French National Institute for Statistics and Economic Studies). All prescriptions of patients affiliated to the compulsory general scheme of Social Security System were retrieved from the French Health Insurance Information System of the Nord-Pas-de-Calais Region. This scheme covers 65.9% of people aged 75 and over in the Nord-Pas-de-Calais Region. Prescriptions for the elderly living in nursing homes with a pharmacy division and those affiliated to another health insurance system were not collected in this study. A total of 209,411 people aged 75 and over were eligible for the study. People who did not have any reimbursed prescription during the study (n = 255; 0.1%) or any prescription with at least one oral or injectable drug (n = 1177; 0.6%) were excluded from the study. Finally, the analysis focused on reimbursed prescriptions for 207,979 people aged 75 and over during the 3-month study period. 2.2. Data collection
631
PIM: medications were classified as inappropriate according to the list of Laroche (Laroche et al., 2007). This list is comprised of 34 criteria divided into three groups: (1) drugs with an unfavorable benefit to risk ratio, (2) drugs with questionable efficacy, and (3) drugs with both an unfavorable benefit to risk ratio and a questionable efficacy. Criteria involving a particular clinical situation (criteria 21–25) and those based on the dose (criteria 14, 27) were not considered, as the database did not contain these data. Anticholinergic score of prescriptions: The anticholinergic effect of prescriptions was measured using the ADS adapted according to the recent study of Dura´n et al. (2013). In this scale, the drugs were rated in an ordinal manner from zero to three. The zero level was assigned to an absence of known anticholinergic activity and level three to a high anticholinergic activity. The anticholinergic score of a given prescription was obtained by summing up levels of all prescribed drugs. This score was calculated for each prescription. For a given patient, only the prescription with the highest anticholinergic score was retained for the analysis. 2.4. Statistical analysis Quantitative variables were described by mean and standard deviation (SD) if the normality hypotheses (Shapiro–Wilks test) were fulfilled and by median and first and third quartiles (Q1, Q3) otherwise. Qualitative variables were described by frequency and percentage. Correlation between variables was performed using the Spearman’s rank test. 3. Results 3.1. Patients January 1 and March 31, 2012, a total of 207,979 people aged 75 years and over had at least one reimbursed prescription containing an oral or injected drug. They represented 99.3% of eligible people and 65.6% of people aged 75 years and over living in the Nord-Pas-de-Calais region. The majority of patients lived in their own home. Patient characteristics are shown in Table 1. 3.2. Polypharmacy is related to the total number of prescriptions per patient rather than the total number of drugs per prescription There was an important difference between the total number of drugs per prescription and the total number of drugs per patient. This result is shown in Fig. 1. The number of drugs per prescription was often relatively low with only one to four drugs prescribed in Table 1 Characteristics of the study population. Patients (n = 207,979)
All prescriptions issued and reimbursed in community pharmacy were extracted over the study period. All data were anonymous. Each prescription was characterized by a patient identifier (anonymous number), the prescribed drugs, the prescriber (anonymous number), the pharmacist who issued the prescription (anonymous number), the dates of prescription and drug delivery. Patient characteristics included age, gender, living at home or in nursing homes. 2.3. Classification of drugs Drugs were coded according to the Anatomical Therapeutic Chemical (ATC) Classification System. Oral or injectable medications were recorded. Eye drops, ointments, and aerosols were excluded from this study.
Age [years; mean (S.D.)] Female Living in nursing home Number of prescriptions during the 3-month study period [median IQR] Number of drugs during the 3-month study period
