CLINICAL INVESTIGATIONS
2012 American Geriatrics Society Beers Criteria: Enhanced Applicability for Detecting Potentially Inappropriate Medications in European Older Adults? A Comparison with the Screening Tool of Older Person’s Potentially Inappropriate Prescriptions Encarnacio´n Blanco-Reina, MD, PhD,* Gabriel Ariza-Zafra, MD, PhD,† Ricardo Oca~ na-Riola, ‡ † PhD, and Matilde Leo´n-Ortiz, MD
OBJECTIVES: To determine the prevalence of potentially inappropriate medications (PIMs) and related factors through a comparative analysis of the Screening Tool of Older Person’s Potentially Inappropriate Prescriptions (STOPP), the 2003 Beers criteria, and the 2012 AGS update of the Beers criteria. DESIGN: Cross-sectional. SETTING: Primary care. PARTICIPANTS: Community-dwelling persons aged 65 and older who live on the island of Lanzarote, Spain (N = 407). MEASUREMENTS: Sociodemographic characteristics; independence in activities of daily living; cognitive function; Geriatric Depression Scale; clinical diagnoses; and complete data on indication, dosage, and length of drug treatments. One thousand eight hundred seventh-two prescriptions were examined, and the rate of PIMs was assessed with the three criteria. The primary endpoint was the percentage of participants receiving at least one PIM. Multivariate logistic regression was used to examine the factors related to PIMs. RESULTS: Potentially inappropriate medications were present in 24.3%, 35.4%, and 44% of participants, according to the 2003 Beers criteria, STOPP, and 2012 Beers criteria, respectively. The profile of PIMs was also different (the most frequent being benzodiazepines in both Beers criteria lists and aspirin in the STOPP). The number of drugs
From the *Pharmacology and Therapeutics Department, Medical School, Ma´laga Biomedical Institute, University of Ma´laga, Ma´laga, †Geriatrics Department, Complejo Hospitalario Universitario of Albacete, Albacete, and ‡Department of Statistics, Andalusian School of Public Health, Granada, Spain. Address correspondence to Encarnacio´n Blanco Reina, Pharmacology and Therapeutics Department, School of Medicine, Campus de Teatinos, Boulevard Louis Pasteur, Malaga 29071, Spain. E-mail: [email protected] DOI: 10.1111/jgs.12891
JAGS 62:1217–1223, 2014 © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society
was associated with risk of prescribing PIMs in all three models, as was the presence of a psychological disorder in the 2003 Beers criteria (odds ratio (OR) = 2.07, 95% confidence interval (CI) = 1.26–3.40) and the 2012 Beers criteria (OR = 2.91, 95% CI = 1.83–4.66). The kappa for degree of agreement between STOPP and the 2012 Beers criteria was 0.35 (95% CI = 0.25–0.44). CONCLUSION: The 2012 Beers criteria detected the highest number of PIMs, and given the scant overlapping with the STOPP criteria, the use of both tools may be seen as complementary. J Am Geriatr Soc 62:1217–1223, 2014.
Key words: potentially inappropriate medications; Beers criteria; Screening Tool of Older Person’s Potentially Inappropriate Prescriptions; older adults
I
nappropriate prescribing in elderly adults is of concern given the association with negative health outcomes, including adverse drug events (ADEs), morbidity, health services use, hospitalization, and economic costs.1–5 Different screening tools have been developed to detect potentially inappropriate prescribing. The Beers criteria, published in 1991, later revised and updated in 1997 and 2003,6–8 was the first and most widely known of these tools and has been used in most research published on potentially inappropriate medications (PIMs), although in Europe, these criteria have several weaknesses, the main one being that many of the drugs on the list are rarely used or unavailable in most European countries. Furthermore, the Beers criteria give no consideration to drug–drug interactions, duration of treatment, varying indications for certain drugs, and underuse of indicated drugs.9 In view of these limitations, the Screening Tool of Older Person’s Potentially Inappropriate Prescriptions (STOPP) and Screening Tool to Alert doctors to the Right Treatment (START)10 have been developed and validated in Europe.
0002-8614/14/$15.00
1218
BLANCO-REINA ET AL.
The STOPP criteria are organized according to physiological system and overcome some of the limitations seen in the Beers criteria. Several studies have shown a higher detection rate for inappropriate prescribing with STOPP than with the Beers criteria.11–13 More recently, with the support of the American Geriatrics Society (AGS), a new update of the Beers criteria has been published—the 2012 AGS Beers criteria—providing a more-dynamic list that is more in line with clinical practice. The inclusion of an evidence-based approach has improved the quality of the criteria. Each criterion now includes a clear recommendation with a given quality of evidence and strength of recommendation. The addition of several recently marketed medications, together with the exclusion of drugs no longer available are further positive points, and another new feature is a third list of drugs to be used with caution in older adults.14,15 There are similarities and differences between the STOPP criteria and the 2012 Beers criteria in the drugs to avoid and drug–disease interactions sections. One of the most consistent findings is that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in older adults is high risk, showing up on drugs to avoid lists and drug–disease interactions with heart failure, chronic renal failure, and peptic ulcer disease. Both lists also include tricyclic antidepressants as a class of drugs that can exacerbate a number of conditions, including falls, fractures, dementia, and cognitive impairment. Differences are also clear, such as the use of NSAIDs in individuals with hypertension for the STOPP criteria, which is not included in the 2012 Beers criteria. Another difference involves benzodiazepine use. Although the two instruments both include long-acting benzodiazepines as drugs to avoid, only the 2012 Beers criteria includes short- and intermediate-acting benzodiazepines as well.16 Further discrepancies highlight the danger of anticholinergic drugs in the 2012 Beers criteria or the limitations for warfarin use included in the STOPP.17 It was felt that it would be interesting to determine whether this update increased the applicability of the Beers criteria in Europe and to compare the criteria with STOPP. Therefore, the present study aimed to determine the prevalence of PIMs in primary care using the 2003 Beers criteria, STOPP, and the 2012 AGS Beers criteria. Additional objectives included comparing specificity and sensitivity, calculating agreement of the different criteria, and analyzing the factors associated with inappropriate prescribing for each for these tools.
METHODS Study Design and Subjects This was a cross-sectional study. The study population comprised all community-dwelling residents aged 65 and older on Lanzarote, Canary Islands, Spain, where there are 15 primary healthcare centers. Stratified random sampling was used to select a representative sample of the population, with proportional allocation of the population for each healthcare center. Individuals aged 65 and older who were living in the community and provided informed consent to take part in the study were included. Considering a mean prevalence of inappropriate prescribing within primary
JULY 2014–VOL. 62, NO. 7
JAGS
care18–20 of 30%, a confidence level of 1 a = 0.95, absolute accuracy of 4.46%, and a design effect of 1.0, an overall sample of 407 participants was reached. Participants were selected randomly within each healthcare center from a general list of healthcare cards issued by the National Health System and provided by the Primary Care Board. Data were collected between 2005 and 2008.
Data Collection Participants were asked over the telephone to participate and were then requested to attend an interview at a healthcare center or at their homes. The main source of data was the interviews with each participant using a structured questionnaire and complemented by review of the packaging of all medications and medical records. In many cases, the primary caregiver was also present at the interview, which allowed the real medication that participants received to be determined as accurately as possible. In the questionnaire, in addition to full details of drug therapy, a wide range of variables were included regarding participant clinical (diseases) and sociodemographic (age, sex) characteristics and functional evaluation, so that these could be compared with those of other populations and to examine the possible risk factors leading to receiving PIMs. Full data were compiled on dosage and duration of drug treatment, and the corresponding Anatomical Therapeutic Chemical classification code was assigned to each drug. Clinical diagnoses were examined, and the Charlson Comorbidity Index (CCI)21 was calculated for each participant. Participants’ independence in activities of daily living was analyzed using the Katz Index,22 their cognitive function using the Short Portable Mental Status Questionnaire,23 and their mood status using the Geriatric Depression Scale (GDS-15).24 Data were also compiled on the use of healthcare resources over the last year (primary care center, emergency visits, hospitalizations). The same two researchers, both specialized geriatrics physicians (GAZ, MLO), conducted all interviews.
Statistical Analysis The percentage of participants receiving at least one PIM was the primary endpoint. This concept was measured using three tools: the 2003 Beers criteria, STOPP, and the 2012 AGS Beers criteria. Exploratory data analysis and frequency tables were used to describe all variables. According to each criterion, chi-square or Fisher tests were used to analyze the differences in PIM prevalence between categories of independent variables. Multivariate logistic regression was used to examine the factors related to PIMs, performing further diagnosis of the model to ensure goodness of fit.25 A generalized standard-error inflation factor was used to ensure no colinearity between independent variables.26 Linearity of the quantitative independent variables was checked through partial regression plots, and goodness of fit was guaranteed using the Hosmer–Lemeshow test.25 A 5% significance level was used to establish statistical significance. A specific model was estimated for each tool. Specificity and sensitivity were assessed using a two-by-two contingency table, and concordance between Beers criteria and
JAGS
JULY 2014–VOL. 62, NO. 7
2012 AGS BEERS CRITERIA VS STOPP FOR PIM SCREENING IN EUROPE
STOPP was estimated using kappa statistics. Statistical data analysis was performed using SPSS (SPSS, Inc., Chicago, IL) and R language. The local clinical research ethics committee granted ethical approval for this study.
RESULTS Characteristics of the Study Population The main characteristics of the study population are shown in Table 1. Four hundred seven participants were included in the present study (57.2% female). Mean participant age was 79.3 8.0 (range 65–100). The average CCI was 1.95, and 34.6% of participants had CCI scores
Table 1. Characteristics of the Study Population (N = 407) Characteristic
Value
Age, mean SD 79.3 8.0 Charlson Comorbidity Index, mean SD 1.9 1.7 Number of medications per participant, 4.5 2.9 mean SD Sex, n (%) Male 174 (42.8) Female 233 (57.2) Katz Index of activities of daily living, n (%) A 174 (42.8) B 100 (24.6) C 51 (12.5) D 16 (3.9) E 10 (2.5) F 26 (6.4) G 30 (7.4) Short Portable Mental Status Questionnaire errors, n (%) 0–2 234 (57.5) 3–4 114 (28) 5–7 20 (4.9) ≥8 39 (9.6) Geriatric Depression Scale-15 score, n (%)a 0–5 149 (43.3) 6–9 130 (37.8) ≥10 65 (18.9) Charlson Comorbidity Index, n (%) 0 104 (25.6) 1–2 162 (39.8) 3–4 103 (25.3) ≥5 38 (9.3) Most Prevalent Chronic Diseases, n (%) Hypertension 233 (57.2) Osteoarticular disease 217 (53.3) Heart disease 163 (40) Peripheral vascular disease 158 (38.8) Gastrointestinal disease 129 (31.7) Psychopathology 125 (30.9) Diabetes mellitus 97 (23.8) ≥1 hospitalizations in preceding year, n (%) 107 (26.2) Receipt of >1 Medications, n (%) Cardiovascular 283 (69.5) Digestive and metabolism 218 (53.6) Nervous system 210 (51.6) SD = standard deviation. a ≤5, no depression; >5, suggestive of depression; >10, almost always depression.
1219
>2. The most common diagnoses were hypertension (57.2%), bone and joint disorders (53.3%), heart disease (40%), and peripheral vascular disease (38.8%); 23.8% had diabetes mellitus. During the preceding year, 26.2% had required hospitalization. Approximately one-third needed assistance with at least two activities of daily living, 57.5% had at least two errors on the Short Portable Mental Status Questionnaire, 43.3% of the participants had normal GDS scores, and 18.9% had a score of 10 or higher, which almost invariably indicates depression. The participants usually took a mean of 4.5 2.9 drugs (range 0–14). The most widely prescribed Anatomical Therapeutic Chemical groups were cardiovascular (69.5% of the participants had ≥1 drugs from this group), digestive and metabolism (53.6%), and nervous system (51.6%). Omeprazole and aspirin were the two most frequently used drugs. Approximately 40% of participants occasionally used a drug, on their own initiative and almost always for symptom relief; in order of frequency, these were benzodiazepines, analgesics (mainly acetaminophen), and laxatives.
Detecting PIMs and Comparing Tools Potentially inappropriate medication use according to the 2003 Beers criteria was identified in 24.3% of participants. Seventy-nine participants (19.4%) were taking one PIM, 19 (4.7%) were taking two, and one was taking three. STOPP criteria detected one to three PIMs in 35.4% of participants. The 2012 AGS Beers criteria identified PIMs in 44% of participants. Most of the older adults were taking a single PIM, although three participants were taking up to four PIMs according to this tool. These data are shown in detail in Table 2. In the bivariate analysis, no statistically significant differences were found in the prevalence of PIMs according to sex or age. The 2003 Beers criteria detected a total of 120 PIMs in the sample, 102 of which were independent of diagnosis and 18 were considering diagnosis. The most common were long-acting benzodiazepines (18.3% of PIMs overall according to the 2003 Beers criteria), noncyclooxygenase selective NSAIDs (long-term use of full-dosage, longer half-life), amiodarone, and fluoxetine (Table 3). The STOPP criteria identified 173 PIMs, 35 of which (20.2%) were aspirin prescribed at a dose of more than 150 mg/d, 28 (16.2%) were long-term long-acting benzodiazepines, 23 (13.3%) glyburide with type 2 diabetes mellitus, and 18 (10.4%) long-term use of NSAIDs (>3 months) for the relief of mild to moderate joint pain with osteoarthritis. As for organ systems, the highest number of PIMs identified with the STOPP criteria were found in the cardiovascular system (39.3%), followed by the central nervous system (21.4%) and the endocrine system (13.3%). When the 2012 AGS Beers criteria were applied, 241 PIMs were detected, most of which were independent of diagnosis (n = 223). Prescription of short- and intermediate-acting benzodiazepines and long-acting benzodiazepines (n = 52 and n = 43, respectively) accounted for the greater number of PIMs detected using the new tool, followed by first- and second-generation antipsychotics in participants with dementia, long-duration sulfonylureas and oral non-cyclooxygenase selective NSAIDs. As a result, central nervous
1220
BLANCO-REINA ET AL.
JULY 2014–VOL. 62, NO. 7
JAGS
Table 2. Number of Participants with Potentially Inappropriate Medications (PIMs) Identified According to the Different Criteria PIMs per Participant
Screening Tool of Older Person’s Potentially Inappropriate Prescriptions
2003 Beers Criteria
0 1 2 3 4 ≥1
308 79 19 1 0 99
(75.7) (19.4) (4.7) (0.2)
263 120 19 5 0 144
(24.3)
2012 American Geriatric Society Beers Criteria
(64.6) (29.5) (4.7) (1.2)
228 130 39 7 3 179
(35.4)
(56) (31.9) (9.6) (1.7) (0.7) (44)
Table 3. The Five Most Frequent Potentially Inappropriate Medications (PIMs) Detected According to the Three Tools 2003 Beers Criteria Order
First Second Third Fourth Fifth
2012 American Geriatrics Society Beers Criteria
Screening Tool of Older Person’s Potentially Inappropriate Prescriptions PIM, n (%)
Benzodiazepine, 22 (18.3)a Noncyclooxygenase NSAID, 20 (16.6)c Amiodarone, 10 (8.3) Fluoxetine, 10 (8.3) Doxazosin, 9 (7.5)
Aspirin, 35 (20.2) Benzodiazepine, 28 (16.2)d
Benzodiazepine, 95 (39.4)b Antipsychotic, 31 (12.8)
Glyburide, 23 (13.3) NSAID, 18 (10.4)e Diuretic,g duplicate class, 9 (5.2)
Sulfonylurea, 23 (9.5) Noncyclooxygenase NSAID, 21 (8.7)f Nonbenzodiazepine hypnotic, 13 (5.8)
a
Long-acting benzodiazepine. Short-, intermediate-, and long-acting benzodiazepines. c Long-term use of full-dosage, longer half-life, noncyclooxygenase selective nonsteroidal anti-inflammatory drug (NSAID). d Long-term, long-acting benzodiazepine and benzodiazepine with long-acting metabolites. e Long-term use of NSAID (>3 months) for relief of mild joint pain in ostearthritis. f Oral noncyclooxygenase selective NSAID for pain. g Loop diuretic as first-line monotherapy for hypertension. b
system drugs give rise to the greatest number of inappropriate prescriptions when applying these criteria (n = 143, 59.3%). The most common PIMs for each of the tools are summarized in Table 3. The list of medications to be used with caution in older adults was also evaluated; an 148 prescriptions of this type were found. For this new list in the 2012 AGS Beers criteria, warnings are provided most frequently for selective serotonin reuptake inhibitors
(32.4% of the total of medications to be used with caution), antipsychotics (26.3%), vasodilators (25%), and aspirin for primary prevention of cardiac events in adults aged 80 and older (8.8%). The different prevalence rates for PIMs and the sensitivity and specificity of each of the screening tools are shown in Table 4. Taking the most widely used criteria as the reference point (2003 Beers), STOPP had a sensitivity
Table 4. Sensitivity, Specificity, and Number of Criteria Used in Each Tool
Variable
2003 Beers Criteriaa
PIMs, n Prevalence of PIMs (95% CI) Used/total items, n/N (%) Sensitivity (95% CI) Specificity (95% CI) Kappa statistic (95% CI)b
120 24.3 (20.4–28.7) 21/68 (30.9) Reference Reference Reference
a
Screening Tool of Older Person’s Potentially Inappropriate Prescriptions
173 35.4 25/65 70.4 75.5 0.39
(30.9–40.1) (38.5) (60.7–78.5) (70.3–79.9) (0.30–0.48)
2012 AGS Beers Criteria
241 44 18/53 84.7 68.6 0.41
(39.2–48.8) (33.9) (76.2–90.5) (63.2–73.5) (0.32–0.50)
Chosen as the reference because it has been the most widely used tool in detection of potentially inappropriate medication (PIM) use. Strength of agreement between Screening Tool of Older Person’s Potentially Inappropriate Prescriptions (STOPP) and 2012 American Geriatric Society (AGS) Beers criteria (j = 0.35, 95% confidence interval (CI) = 0.25–0.44). b
JAGS
JULY 2014–VOL. 62, NO. 7
2012 AGS BEERS CRITERIA VS STOPP FOR PIM SCREENING IN EUROPE
of 70.4% and a specificity of 75.5% to detect PIMs. In the case of the 2012 Beers criteria, sensitivity to detect PIMs reached 84.7%, and specificity was 68.6%. The measure of agreement or kappa index was 0.396 (P < .001) between STOPP and the 2003 Beers criteria, 0.416 (P < .001) between the 2012 AGS Beers and the 2003 Beers criteria, and 0.353 (P < .001) between STOPP and the 2012 Beers criteria. Twenty-one of the 68 Beers criteria, 25 of the 65 STOPP items, and 18 of the 53 criteria in the updated 2012 Beers tool were used to detect inappropriate prescribing (Table 4). In any event, only approximately one-third of the items in these tools were of use in detecting all PIMs.
Risk Factors for Potentially Inappropriate Prescribing According to the Beers 2003, the risk of PIMs was greater with more drugs (odds ratio (OR) = 1.18, 95% confidence interval (CI) = 1.09–1.29) and a diagnosis of a mental disorder (OR = 2.07, 95% CI = 1.26–3.40). More medications also predicted the use of a PIM according to STOPP criteria (OR = 1.16, 95% CI = 1.08–1.25). According to the logistic regression model for the 2012 AGS Beers criteria, the risk of a PIM would be 21% greater for each drug added (OR = 1.21, 95% CI = 1.12–1.32), and the presence of a psychological disorder was found to be an influential predictor of PIM use (OR = 2.91, 95% CI = 1.83–4.66). There was no statistically significant association between sex or age and PIMs (Table 5).
DISCUSSION The prevalence and pattern of PIMs varied considerably according to the different tools. According to the 2003 Beers criteria, one-quarter of participants received an inappropriate prescription. Although numerous studies use this tool, the current study focused only on comparisons of interest in participants living in the community. The figures obtained for Lanzarote are similar to previously published figures in Madrid, Spain (24%)19 and are consistent with those from other international papers in Europe (~20%),27–29 Asia (23.7%),30 and the United States (23.3%).31 In the United Kingdom, studies conducted on databases revealed a prevalence of 32%.32,33 Even higher percentages were reported in Australia (48.7%)34 and Lebanon (59.6%).35 The high degree of variability in
1221
prevalence outcomes is clear despite the fact that only studies conducted in the same healthcare context (primary care) and on the use of the same tool throughout were compared with the current study. These differences were also revealed in the countries participating in a multicenter European study.29 Multiple factors may be responsible for this variability, although the differences in availability of certain drugs and prescribing habits may account for the major share of the differences. As a result, all comparisons must be made with caution, and other possible sources of variability must be taken into account, such as how the criteria are applied (e.g., some studies do not include “considering diagnosis” criteria) and sample selection (e.g., cutoff for age and any clinical, social, or functional characteristic that may account for differences in drug use). The single factor that was common to most studies was the use of long-half-life benzodiazepines or high doses of short-half-life benzodiazepines as the most frequent PIM.18,27,29,34,36,37 Potentially inappropriate medication detection increased to 35% when the STOPP criteria were applied. The comparison of outcomes was more limited with these criteria because they were more recent and had been used mainly within Europe. The prevalence data are fairly consistent with two Irish studies (36% and 34%, respectively), which used prescribing databases.5,20 In terms of methodology, another study in Ireland is probably the closest to the current one, although the PIM rates found in that study were considerably lower (21.4%).18 This difference may stem from the fact that baseline status in the Irish sample was better because terminally ill individuals were excluded, the mean age was 4.5 years younger, and the CCI was 0.67 (vs 1.95 in the current study sample); that is, these individuals were younger and had lesser disease burden. Higher prevalence rates (~50%) can also be seen, albeit in a different context (the hospital setting),12,38 or even higher rates (70%) for long-term care residents.13 The current study found clearly differentiated patterns in the drugs involved mainly in the PIMs detected according to STOPP. Although aspirin at doses over 150 mg/d was the most frequent PIM on Lanzarote, proton pump inhibitors for peptic ulcers at the full therapeutic dose for 8 weeks was the most frequent PIM in the Irish studies.5,18,20 The effect of geographic location on prescribing patterns needs to be rethought because there are widely differing sociocultural, economic, and especially, healthcare components in each location. In any event and
Table 5. Multivariate Logistic Regression for Having at Least One Potentially Inappropriate Medication According to Three Tools 2003 Beers Criteria Characteristic
Age Number of medications Male ≥1 psychiatric disorders p
2012 American Geriatrics Society Beers Criteria: Enhanced Applicability for Detecting Potentially Inappropriate Medications in European Older Adults? A Comparison with the Screening Tool of Older Person’s Potentially Inappropriate Prescriptions Encarnacio´n Blanco-Reina, MD, PhD,* Gabriel Ariza-Zafra, MD, PhD,† Ricardo Oca~ na-Riola, ‡ † PhD, and Matilde Leo´n-Ortiz, MD
OBJECTIVES: To determine the prevalence of potentially inappropriate medications (PIMs) and related factors through a comparative analysis of the Screening Tool of Older Person’s Potentially Inappropriate Prescriptions (STOPP), the 2003 Beers criteria, and the 2012 AGS update of the Beers criteria. DESIGN: Cross-sectional. SETTING: Primary care. PARTICIPANTS: Community-dwelling persons aged 65 and older who live on the island of Lanzarote, Spain (N = 407). MEASUREMENTS: Sociodemographic characteristics; independence in activities of daily living; cognitive function; Geriatric Depression Scale; clinical diagnoses; and complete data on indication, dosage, and length of drug treatments. One thousand eight hundred seventh-two prescriptions were examined, and the rate of PIMs was assessed with the three criteria. The primary endpoint was the percentage of participants receiving at least one PIM. Multivariate logistic regression was used to examine the factors related to PIMs. RESULTS: Potentially inappropriate medications were present in 24.3%, 35.4%, and 44% of participants, according to the 2003 Beers criteria, STOPP, and 2012 Beers criteria, respectively. The profile of PIMs was also different (the most frequent being benzodiazepines in both Beers criteria lists and aspirin in the STOPP). The number of drugs
From the *Pharmacology and Therapeutics Department, Medical School, Ma´laga Biomedical Institute, University of Ma´laga, Ma´laga, †Geriatrics Department, Complejo Hospitalario Universitario of Albacete, Albacete, and ‡Department of Statistics, Andalusian School of Public Health, Granada, Spain. Address correspondence to Encarnacio´n Blanco Reina, Pharmacology and Therapeutics Department, School of Medicine, Campus de Teatinos, Boulevard Louis Pasteur, Malaga 29071, Spain. E-mail: [email protected] DOI: 10.1111/jgs.12891
JAGS 62:1217–1223, 2014 © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society
was associated with risk of prescribing PIMs in all three models, as was the presence of a psychological disorder in the 2003 Beers criteria (odds ratio (OR) = 2.07, 95% confidence interval (CI) = 1.26–3.40) and the 2012 Beers criteria (OR = 2.91, 95% CI = 1.83–4.66). The kappa for degree of agreement between STOPP and the 2012 Beers criteria was 0.35 (95% CI = 0.25–0.44). CONCLUSION: The 2012 Beers criteria detected the highest number of PIMs, and given the scant overlapping with the STOPP criteria, the use of both tools may be seen as complementary. J Am Geriatr Soc 62:1217–1223, 2014.
Key words: potentially inappropriate medications; Beers criteria; Screening Tool of Older Person’s Potentially Inappropriate Prescriptions; older adults
I
nappropriate prescribing in elderly adults is of concern given the association with negative health outcomes, including adverse drug events (ADEs), morbidity, health services use, hospitalization, and economic costs.1–5 Different screening tools have been developed to detect potentially inappropriate prescribing. The Beers criteria, published in 1991, later revised and updated in 1997 and 2003,6–8 was the first and most widely known of these tools and has been used in most research published on potentially inappropriate medications (PIMs), although in Europe, these criteria have several weaknesses, the main one being that many of the drugs on the list are rarely used or unavailable in most European countries. Furthermore, the Beers criteria give no consideration to drug–drug interactions, duration of treatment, varying indications for certain drugs, and underuse of indicated drugs.9 In view of these limitations, the Screening Tool of Older Person’s Potentially Inappropriate Prescriptions (STOPP) and Screening Tool to Alert doctors to the Right Treatment (START)10 have been developed and validated in Europe.
0002-8614/14/$15.00
1218
BLANCO-REINA ET AL.
The STOPP criteria are organized according to physiological system and overcome some of the limitations seen in the Beers criteria. Several studies have shown a higher detection rate for inappropriate prescribing with STOPP than with the Beers criteria.11–13 More recently, with the support of the American Geriatrics Society (AGS), a new update of the Beers criteria has been published—the 2012 AGS Beers criteria—providing a more-dynamic list that is more in line with clinical practice. The inclusion of an evidence-based approach has improved the quality of the criteria. Each criterion now includes a clear recommendation with a given quality of evidence and strength of recommendation. The addition of several recently marketed medications, together with the exclusion of drugs no longer available are further positive points, and another new feature is a third list of drugs to be used with caution in older adults.14,15 There are similarities and differences between the STOPP criteria and the 2012 Beers criteria in the drugs to avoid and drug–disease interactions sections. One of the most consistent findings is that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in older adults is high risk, showing up on drugs to avoid lists and drug–disease interactions with heart failure, chronic renal failure, and peptic ulcer disease. Both lists also include tricyclic antidepressants as a class of drugs that can exacerbate a number of conditions, including falls, fractures, dementia, and cognitive impairment. Differences are also clear, such as the use of NSAIDs in individuals with hypertension for the STOPP criteria, which is not included in the 2012 Beers criteria. Another difference involves benzodiazepine use. Although the two instruments both include long-acting benzodiazepines as drugs to avoid, only the 2012 Beers criteria includes short- and intermediate-acting benzodiazepines as well.16 Further discrepancies highlight the danger of anticholinergic drugs in the 2012 Beers criteria or the limitations for warfarin use included in the STOPP.17 It was felt that it would be interesting to determine whether this update increased the applicability of the Beers criteria in Europe and to compare the criteria with STOPP. Therefore, the present study aimed to determine the prevalence of PIMs in primary care using the 2003 Beers criteria, STOPP, and the 2012 AGS Beers criteria. Additional objectives included comparing specificity and sensitivity, calculating agreement of the different criteria, and analyzing the factors associated with inappropriate prescribing for each for these tools.
METHODS Study Design and Subjects This was a cross-sectional study. The study population comprised all community-dwelling residents aged 65 and older on Lanzarote, Canary Islands, Spain, where there are 15 primary healthcare centers. Stratified random sampling was used to select a representative sample of the population, with proportional allocation of the population for each healthcare center. Individuals aged 65 and older who were living in the community and provided informed consent to take part in the study were included. Considering a mean prevalence of inappropriate prescribing within primary
JULY 2014–VOL. 62, NO. 7
JAGS
care18–20 of 30%, a confidence level of 1 a = 0.95, absolute accuracy of 4.46%, and a design effect of 1.0, an overall sample of 407 participants was reached. Participants were selected randomly within each healthcare center from a general list of healthcare cards issued by the National Health System and provided by the Primary Care Board. Data were collected between 2005 and 2008.
Data Collection Participants were asked over the telephone to participate and were then requested to attend an interview at a healthcare center or at their homes. The main source of data was the interviews with each participant using a structured questionnaire and complemented by review of the packaging of all medications and medical records. In many cases, the primary caregiver was also present at the interview, which allowed the real medication that participants received to be determined as accurately as possible. In the questionnaire, in addition to full details of drug therapy, a wide range of variables were included regarding participant clinical (diseases) and sociodemographic (age, sex) characteristics and functional evaluation, so that these could be compared with those of other populations and to examine the possible risk factors leading to receiving PIMs. Full data were compiled on dosage and duration of drug treatment, and the corresponding Anatomical Therapeutic Chemical classification code was assigned to each drug. Clinical diagnoses were examined, and the Charlson Comorbidity Index (CCI)21 was calculated for each participant. Participants’ independence in activities of daily living was analyzed using the Katz Index,22 their cognitive function using the Short Portable Mental Status Questionnaire,23 and their mood status using the Geriatric Depression Scale (GDS-15).24 Data were also compiled on the use of healthcare resources over the last year (primary care center, emergency visits, hospitalizations). The same two researchers, both specialized geriatrics physicians (GAZ, MLO), conducted all interviews.
Statistical Analysis The percentage of participants receiving at least one PIM was the primary endpoint. This concept was measured using three tools: the 2003 Beers criteria, STOPP, and the 2012 AGS Beers criteria. Exploratory data analysis and frequency tables were used to describe all variables. According to each criterion, chi-square or Fisher tests were used to analyze the differences in PIM prevalence between categories of independent variables. Multivariate logistic regression was used to examine the factors related to PIMs, performing further diagnosis of the model to ensure goodness of fit.25 A generalized standard-error inflation factor was used to ensure no colinearity between independent variables.26 Linearity of the quantitative independent variables was checked through partial regression plots, and goodness of fit was guaranteed using the Hosmer–Lemeshow test.25 A 5% significance level was used to establish statistical significance. A specific model was estimated for each tool. Specificity and sensitivity were assessed using a two-by-two contingency table, and concordance between Beers criteria and
JAGS
JULY 2014–VOL. 62, NO. 7
2012 AGS BEERS CRITERIA VS STOPP FOR PIM SCREENING IN EUROPE
STOPP was estimated using kappa statistics. Statistical data analysis was performed using SPSS (SPSS, Inc., Chicago, IL) and R language. The local clinical research ethics committee granted ethical approval for this study.
RESULTS Characteristics of the Study Population The main characteristics of the study population are shown in Table 1. Four hundred seven participants were included in the present study (57.2% female). Mean participant age was 79.3 8.0 (range 65–100). The average CCI was 1.95, and 34.6% of participants had CCI scores
Table 1. Characteristics of the Study Population (N = 407) Characteristic
Value
Age, mean SD 79.3 8.0 Charlson Comorbidity Index, mean SD 1.9 1.7 Number of medications per participant, 4.5 2.9 mean SD Sex, n (%) Male 174 (42.8) Female 233 (57.2) Katz Index of activities of daily living, n (%) A 174 (42.8) B 100 (24.6) C 51 (12.5) D 16 (3.9) E 10 (2.5) F 26 (6.4) G 30 (7.4) Short Portable Mental Status Questionnaire errors, n (%) 0–2 234 (57.5) 3–4 114 (28) 5–7 20 (4.9) ≥8 39 (9.6) Geriatric Depression Scale-15 score, n (%)a 0–5 149 (43.3) 6–9 130 (37.8) ≥10 65 (18.9) Charlson Comorbidity Index, n (%) 0 104 (25.6) 1–2 162 (39.8) 3–4 103 (25.3) ≥5 38 (9.3) Most Prevalent Chronic Diseases, n (%) Hypertension 233 (57.2) Osteoarticular disease 217 (53.3) Heart disease 163 (40) Peripheral vascular disease 158 (38.8) Gastrointestinal disease 129 (31.7) Psychopathology 125 (30.9) Diabetes mellitus 97 (23.8) ≥1 hospitalizations in preceding year, n (%) 107 (26.2) Receipt of >1 Medications, n (%) Cardiovascular 283 (69.5) Digestive and metabolism 218 (53.6) Nervous system 210 (51.6) SD = standard deviation. a ≤5, no depression; >5, suggestive of depression; >10, almost always depression.
1219
>2. The most common diagnoses were hypertension (57.2%), bone and joint disorders (53.3%), heart disease (40%), and peripheral vascular disease (38.8%); 23.8% had diabetes mellitus. During the preceding year, 26.2% had required hospitalization. Approximately one-third needed assistance with at least two activities of daily living, 57.5% had at least two errors on the Short Portable Mental Status Questionnaire, 43.3% of the participants had normal GDS scores, and 18.9% had a score of 10 or higher, which almost invariably indicates depression. The participants usually took a mean of 4.5 2.9 drugs (range 0–14). The most widely prescribed Anatomical Therapeutic Chemical groups were cardiovascular (69.5% of the participants had ≥1 drugs from this group), digestive and metabolism (53.6%), and nervous system (51.6%). Omeprazole and aspirin were the two most frequently used drugs. Approximately 40% of participants occasionally used a drug, on their own initiative and almost always for symptom relief; in order of frequency, these were benzodiazepines, analgesics (mainly acetaminophen), and laxatives.
Detecting PIMs and Comparing Tools Potentially inappropriate medication use according to the 2003 Beers criteria was identified in 24.3% of participants. Seventy-nine participants (19.4%) were taking one PIM, 19 (4.7%) were taking two, and one was taking three. STOPP criteria detected one to three PIMs in 35.4% of participants. The 2012 AGS Beers criteria identified PIMs in 44% of participants. Most of the older adults were taking a single PIM, although three participants were taking up to four PIMs according to this tool. These data are shown in detail in Table 2. In the bivariate analysis, no statistically significant differences were found in the prevalence of PIMs according to sex or age. The 2003 Beers criteria detected a total of 120 PIMs in the sample, 102 of which were independent of diagnosis and 18 were considering diagnosis. The most common were long-acting benzodiazepines (18.3% of PIMs overall according to the 2003 Beers criteria), noncyclooxygenase selective NSAIDs (long-term use of full-dosage, longer half-life), amiodarone, and fluoxetine (Table 3). The STOPP criteria identified 173 PIMs, 35 of which (20.2%) were aspirin prescribed at a dose of more than 150 mg/d, 28 (16.2%) were long-term long-acting benzodiazepines, 23 (13.3%) glyburide with type 2 diabetes mellitus, and 18 (10.4%) long-term use of NSAIDs (>3 months) for the relief of mild to moderate joint pain with osteoarthritis. As for organ systems, the highest number of PIMs identified with the STOPP criteria were found in the cardiovascular system (39.3%), followed by the central nervous system (21.4%) and the endocrine system (13.3%). When the 2012 AGS Beers criteria were applied, 241 PIMs were detected, most of which were independent of diagnosis (n = 223). Prescription of short- and intermediate-acting benzodiazepines and long-acting benzodiazepines (n = 52 and n = 43, respectively) accounted for the greater number of PIMs detected using the new tool, followed by first- and second-generation antipsychotics in participants with dementia, long-duration sulfonylureas and oral non-cyclooxygenase selective NSAIDs. As a result, central nervous
1220
BLANCO-REINA ET AL.
JULY 2014–VOL. 62, NO. 7
JAGS
Table 2. Number of Participants with Potentially Inappropriate Medications (PIMs) Identified According to the Different Criteria PIMs per Participant
Screening Tool of Older Person’s Potentially Inappropriate Prescriptions
2003 Beers Criteria
0 1 2 3 4 ≥1
308 79 19 1 0 99
(75.7) (19.4) (4.7) (0.2)
263 120 19 5 0 144
(24.3)
2012 American Geriatric Society Beers Criteria
(64.6) (29.5) (4.7) (1.2)
228 130 39 7 3 179
(35.4)
(56) (31.9) (9.6) (1.7) (0.7) (44)
Table 3. The Five Most Frequent Potentially Inappropriate Medications (PIMs) Detected According to the Three Tools 2003 Beers Criteria Order
First Second Third Fourth Fifth
2012 American Geriatrics Society Beers Criteria
Screening Tool of Older Person’s Potentially Inappropriate Prescriptions PIM, n (%)
Benzodiazepine, 22 (18.3)a Noncyclooxygenase NSAID, 20 (16.6)c Amiodarone, 10 (8.3) Fluoxetine, 10 (8.3) Doxazosin, 9 (7.5)
Aspirin, 35 (20.2) Benzodiazepine, 28 (16.2)d
Benzodiazepine, 95 (39.4)b Antipsychotic, 31 (12.8)
Glyburide, 23 (13.3) NSAID, 18 (10.4)e Diuretic,g duplicate class, 9 (5.2)
Sulfonylurea, 23 (9.5) Noncyclooxygenase NSAID, 21 (8.7)f Nonbenzodiazepine hypnotic, 13 (5.8)
a
Long-acting benzodiazepine. Short-, intermediate-, and long-acting benzodiazepines. c Long-term use of full-dosage, longer half-life, noncyclooxygenase selective nonsteroidal anti-inflammatory drug (NSAID). d Long-term, long-acting benzodiazepine and benzodiazepine with long-acting metabolites. e Long-term use of NSAID (>3 months) for relief of mild joint pain in ostearthritis. f Oral noncyclooxygenase selective NSAID for pain. g Loop diuretic as first-line monotherapy for hypertension. b
system drugs give rise to the greatest number of inappropriate prescriptions when applying these criteria (n = 143, 59.3%). The most common PIMs for each of the tools are summarized in Table 3. The list of medications to be used with caution in older adults was also evaluated; an 148 prescriptions of this type were found. For this new list in the 2012 AGS Beers criteria, warnings are provided most frequently for selective serotonin reuptake inhibitors
(32.4% of the total of medications to be used with caution), antipsychotics (26.3%), vasodilators (25%), and aspirin for primary prevention of cardiac events in adults aged 80 and older (8.8%). The different prevalence rates for PIMs and the sensitivity and specificity of each of the screening tools are shown in Table 4. Taking the most widely used criteria as the reference point (2003 Beers), STOPP had a sensitivity
Table 4. Sensitivity, Specificity, and Number of Criteria Used in Each Tool
Variable
2003 Beers Criteriaa
PIMs, n Prevalence of PIMs (95% CI) Used/total items, n/N (%) Sensitivity (95% CI) Specificity (95% CI) Kappa statistic (95% CI)b
120 24.3 (20.4–28.7) 21/68 (30.9) Reference Reference Reference
a
Screening Tool of Older Person’s Potentially Inappropriate Prescriptions
173 35.4 25/65 70.4 75.5 0.39
(30.9–40.1) (38.5) (60.7–78.5) (70.3–79.9) (0.30–0.48)
2012 AGS Beers Criteria
241 44 18/53 84.7 68.6 0.41
(39.2–48.8) (33.9) (76.2–90.5) (63.2–73.5) (0.32–0.50)
Chosen as the reference because it has been the most widely used tool in detection of potentially inappropriate medication (PIM) use. Strength of agreement between Screening Tool of Older Person’s Potentially Inappropriate Prescriptions (STOPP) and 2012 American Geriatric Society (AGS) Beers criteria (j = 0.35, 95% confidence interval (CI) = 0.25–0.44). b
JAGS
JULY 2014–VOL. 62, NO. 7
2012 AGS BEERS CRITERIA VS STOPP FOR PIM SCREENING IN EUROPE
of 70.4% and a specificity of 75.5% to detect PIMs. In the case of the 2012 Beers criteria, sensitivity to detect PIMs reached 84.7%, and specificity was 68.6%. The measure of agreement or kappa index was 0.396 (P < .001) between STOPP and the 2003 Beers criteria, 0.416 (P < .001) between the 2012 AGS Beers and the 2003 Beers criteria, and 0.353 (P < .001) between STOPP and the 2012 Beers criteria. Twenty-one of the 68 Beers criteria, 25 of the 65 STOPP items, and 18 of the 53 criteria in the updated 2012 Beers tool were used to detect inappropriate prescribing (Table 4). In any event, only approximately one-third of the items in these tools were of use in detecting all PIMs.
Risk Factors for Potentially Inappropriate Prescribing According to the Beers 2003, the risk of PIMs was greater with more drugs (odds ratio (OR) = 1.18, 95% confidence interval (CI) = 1.09–1.29) and a diagnosis of a mental disorder (OR = 2.07, 95% CI = 1.26–3.40). More medications also predicted the use of a PIM according to STOPP criteria (OR = 1.16, 95% CI = 1.08–1.25). According to the logistic regression model for the 2012 AGS Beers criteria, the risk of a PIM would be 21% greater for each drug added (OR = 1.21, 95% CI = 1.12–1.32), and the presence of a psychological disorder was found to be an influential predictor of PIM use (OR = 2.91, 95% CI = 1.83–4.66). There was no statistically significant association between sex or age and PIMs (Table 5).
DISCUSSION The prevalence and pattern of PIMs varied considerably according to the different tools. According to the 2003 Beers criteria, one-quarter of participants received an inappropriate prescription. Although numerous studies use this tool, the current study focused only on comparisons of interest in participants living in the community. The figures obtained for Lanzarote are similar to previously published figures in Madrid, Spain (24%)19 and are consistent with those from other international papers in Europe (~20%),27–29 Asia (23.7%),30 and the United States (23.3%).31 In the United Kingdom, studies conducted on databases revealed a prevalence of 32%.32,33 Even higher percentages were reported in Australia (48.7%)34 and Lebanon (59.6%).35 The high degree of variability in
1221
prevalence outcomes is clear despite the fact that only studies conducted in the same healthcare context (primary care) and on the use of the same tool throughout were compared with the current study. These differences were also revealed in the countries participating in a multicenter European study.29 Multiple factors may be responsible for this variability, although the differences in availability of certain drugs and prescribing habits may account for the major share of the differences. As a result, all comparisons must be made with caution, and other possible sources of variability must be taken into account, such as how the criteria are applied (e.g., some studies do not include “considering diagnosis” criteria) and sample selection (e.g., cutoff for age and any clinical, social, or functional characteristic that may account for differences in drug use). The single factor that was common to most studies was the use of long-half-life benzodiazepines or high doses of short-half-life benzodiazepines as the most frequent PIM.18,27,29,34,36,37 Potentially inappropriate medication detection increased to 35% when the STOPP criteria were applied. The comparison of outcomes was more limited with these criteria because they were more recent and had been used mainly within Europe. The prevalence data are fairly consistent with two Irish studies (36% and 34%, respectively), which used prescribing databases.5,20 In terms of methodology, another study in Ireland is probably the closest to the current one, although the PIM rates found in that study were considerably lower (21.4%).18 This difference may stem from the fact that baseline status in the Irish sample was better because terminally ill individuals were excluded, the mean age was 4.5 years younger, and the CCI was 0.67 (vs 1.95 in the current study sample); that is, these individuals were younger and had lesser disease burden. Higher prevalence rates (~50%) can also be seen, albeit in a different context (the hospital setting),12,38 or even higher rates (70%) for long-term care residents.13 The current study found clearly differentiated patterns in the drugs involved mainly in the PIMs detected according to STOPP. Although aspirin at doses over 150 mg/d was the most frequent PIM on Lanzarote, proton pump inhibitors for peptic ulcers at the full therapeutic dose for 8 weeks was the most frequent PIM in the Irish studies.5,18,20 The effect of geographic location on prescribing patterns needs to be rethought because there are widely differing sociocultural, economic, and especially, healthcare components in each location. In any event and
Table 5. Multivariate Logistic Regression for Having at Least One Potentially Inappropriate Medication According to Three Tools 2003 Beers Criteria Characteristic
Age Number of medications Male ≥1 psychiatric disorders p
