Clinical and Economic Outcomes Associated With Potentially Inappropriate Prescribing in the Elderly

Clinical and economic outcomes associated with the use of specific potentially inappropriate medications in the elderly were evaluated.

Published Online: January 01, 2010
Karen M. Stockl, PharmD; Lisa Le, MS; Shaoang Zhang, PhD; and Ann S. M. Harada, PhD

Objective: To evaluate the risk of adverse events (AEs) and the healthcare costs for elderly patients receiving specific potentially inappropriate medications (PIMs).

Study Design: Retrospective cohort study.

Methods: Patients 65 years and older who started 1 of 23 PIMs were matched with control subjects who were not receiving PIMs. The following 4 AEs and PIMs were evaluated: delirium or hallucinations with Beers high-severity (BHS) anticholinergics, delirium or hallucinations with BHS narcotics (meperidine hydrochloride or pentazocine lactate or pentazocine hydrochloride), extrapyramidal effects with trimethobenzamide hydrochloride, and falls or fractures with BHS sedative hypnotics. The risk of having the AE of interest within 360 days and the annual healthcare costs were examined.

Results: Patients receiving BHS sedative hypnotics were significantly more likely to have a fall or fracture than controls (hazard ratio, 1.22; 95% confidence interval [CI], 1.10-1.35). Patients receiving BHS anticholinergics did not have higher risk of delirium or hallucinations than controls (hazard ratio, 1.03; 95% CI, 0.91-1.16). Delirium or hallucinations occurred at a higher rate among patients receiving BHS narcotics, and extrapyramidal effects occurred at a higher rate among patients receiving trimethobenzamide; however, too few events occurred to assess statistical significance. For all PIMs evaluated, annual adjusted medical and total healthcare costs were significantly higher for patients exposed to PIMs than for controls.

Conclusion: The use of certain BHS PIMs in the elderly may increase AEs or healthcare costs.

(Am J Manag Care. 2010;16(1):e1-e10)

Despite widespread adoption of the Beers list of potentially inappropriate medications (PIMs) in the elderly, outcomes data are limited. Clinical and economic outcomes associated with the use of specific PIMs in the elderly were evaluated.

  • Patients using Beers high-severity sedative hypnotics had increased risk of falls or fractures.
  • Increased risk of delirium or hallucinations was not observed for patients using highseverity anticholinergics.
  • Beers high-severity narcotics and trimethobenzamide hydrochloride may increase the rate of adverse events.
  • For all PIMs evaluated, medical costs were significantly higher for patients exposed to PIMs than for control subjects.
Developed in 1997 to improve the quality of pharmaceutical care, criteria by Beers1 have been widely used to identify potentially inappropriate medication (PIM) use in the elderly. In 2002, the Beers criteria were updated to incorporate new information from scientific literature.2 Severity ratings (high vs low) were assigned to each of the medications. Because some medications listed in the Beers criteria may be justified for certain patients, Zhan et al3 convened an expert panel to classify the Beers criteria into the following 3 categories: (1) drugs that should always be avoided by the elderly, (2) drugs that are rarely appropriate for the elderly, and (3) drugs that have some indications but are often misused.

Clinicians and managed care organizations (MCOs) have adopted the Beers criteria to help identify and target elderly members who may be at risk of adverse events (AEs) due to their use of PIMs. Starting in 2006, the National Committee for Quality Assurance4,5 has included a Healthcare Effectiveness Data and Information Set (HEDIS) performance measure for MCOs to evaluate the percentage of elderly members who received PIMs. The specifications for this HEDIS measure are based on the Beers criteria.

Despite the wide adoption of the Beers criteria within managed care, outcomes data associated with using these PIMs in the elderly are limited. While MCOs are tasked with developing clinical programs to decrease the use of PIMs in the elderly, it is unknown which specific PIMs are most beneficial to target to improve clinical outcomes and reduce healthcare costs. Because the Beers criteria were developed solely based on an expert consensus panel and have not been studied in controlled clinical trials, it has not been proven that reducing PIM use in the elderly prevents adverse clinical outcomes. Although retrospective claims analyses have examined healthcare expenditures or AEs among elderly patients receiving PIMs in the community setting,6-9 these studies grouped together patients with different types of PIMs and did not thoroughly examine outcomes associated with specific PIMs. Because outcomes may vary for different PIMs, studies evaluating specific PIMs are necessary to build stronger evidence that the use of PIMs leads to adverse outcomes in the elderly.

We tested the hypothesis that the use of specific Beers high-severity (BHS) medications designated as “always avoid” or “rarely appropriate” in the elderly would result in increased AEs and healthcare costs. Using retrospective claims data, we evaluated the risk of selected AEs and healthcare costs for elderly patients receiving specific BHS PIMs versus comparable elderly patients not receiving PIMs.


This was a retrospective cohort study using electronic pharmacy and medical claims from an MCO based in the western United States. To focus the analysis on a limited number of medications that would have a higher likelihood of causing AEs, medications were evaluated if they had a severity rating of “high” using the Beers criteria2 and were classified as “always avoid” or “rarely appropriate” by Zhan et al.3 Based on potential adverse outcomes that could occur in the elderly as reported in the Beers criteria2 or other literature sources,10,11 these medications fell within the following 5 AE categories: delirium or hallucinations related to BHS anticholinergic use, delirium or hallucinations related to BHS narcotic use, extrapyramidal AEs related to trimethobenzamide hydrochloride use, falls or fractures related to BHS sedative hypnotic use, and hypoglycemia related to chlorpropamide use. Because only 40 patients receiving chlorpropamide were identified, the last category was not included in the evaluation. A total of 23 medications and 4 AE categories were evaluated (Table 1).

Patient Identification and Matching

Patients 65 years and older were identified if they started 1 of 23 PIMs listed in Table 1 (with no prior use during the 180-day preperiod) during the identification period from January 2003 through June 2005. The date of the first prescription of the PIM during the identification period was defined as the index date. Patients 65 years and older who were not receiving the PIM or another PIM within the same AE category were selected as potential control subjects. For controls, an index date was randomly selected within the identification period. Table 2 gives additional inclusion and exclusion criteria that were applied for the different cohorts. The final cohorts were obtained by matching controls with patients exposed to a PIM on a 1:1 basis using the propensity score method.12 Independent variables used to calculate the propensity score for matching are given in Table 2. Matching was performed in a stepwise fashion; pairs were matched using the lowest window (propensity score, 0.0000001), and then the window was gradually extended by a factor of 10 until reaching 0.1.

Outcomes Variables

The primary outcome was the risk of having the AE of interest during a postperiod of up to 360 days for exposed patients versus controls. The AEs of interest were delirium or hallucinations for the BHS anticholinergics, delirium or hallucinations for the BHS narcotics, extrapyramidal effects for trimethobenzamide, and falls or fractures for the BHS sedative hypnotics. Patients were designated as having the AE of interest if they had an inpatient hospitalization, an emergency department visit, or 2 medical claims with a primary diagnosis code representing the AE (Table 1).

Patients were followed up from the index date until the first date when one of the following conditions occurred: (1) the patient discontinued the index medication (defined as a gap of >30 days past the end of supply date for the last prescription for the index medication and the end of the postperiod), (2) the patient in the anticholinergic or narcotic medication evaluation filled a BHS anticholinergic or narcotic other than the index medication, (3) the patient in the control group for trimethobenzamide filled trimethobenzamide, (4) the patient in the sedative hypnotic evaluation filled a BHS sedative hypnotic other than the index medication, (5) the patient reached the end of the 360-day postperiod, or (6) the patient had an AE of interest.

Pharmacy ingredient costs, medical charges, and total healthcare costs (pharmacy plus medical) were measured for exposed patients versus controls over the 360-day postperiod. Adjusted costs were estimated for the cohorts after controlling for potential confounding factors.

Statistical Analysis

Propensity scores were estimated using logistic regression analysis. Proportional hazards regression was used to analyze the relative risk of having the target AE for exposed patients versus controls. Patients who did not have the target AE were censored at their end of follow-up.

Costs were evaluated using t tests for means, Wilcoxon rank sum tests for medians, and generalized linear models (GLMs) with a log link and gamma distribution for adjusted costs. Adjustment variables included in the GLMs were age, sex, health plan type, geographic state, Charlson Comorbidity Index13 (calculated during the preperiod using a method adapted for electronic claims databases14), and preperiod costs. Statistical analysis was performed using SAS version 9.1 (SAS Institute, Inc, Cary, NC). All comparisons were 2-sided with a .05 level of significance.


BHS Anticholinergics

Among 37,358 pairs of patients exposed to BHS anticholinergics and controls, baseline characteristics were similar except that exposed patients filled more days supply for anticholinergics during the preperiod (Table 3). Exposed patients also had higher preperiod medical costs than


Patients exposed to BHS anticholinergics experienced 15.60 cases of delirium or hallucinations per 1000 person-years compared with 15.18 cases per 1000 person-years for controls (Table 4). The risk of delirium or hallucinations was not significantly different between patients exposed to BHS anticholinergics compared with controls (hazard ratio, 1.03; 95% confidence interval [CI], 0.91-1.16).

Compared with controls, exposed patients had lower adjusted pharmacy costs ($773 vs $796) but higher adjusted medical costs ($17,154 vs $15,214) and higher adjusted total healthcare costs ($18,398 vs $16,482) during the postperiod (P <.001 for all). These results are given in Table 5.

BHS Narcotics

The 395 patients who met the identification criteria for exposure to BHS narcotics were matched with controls having similar characteristics (Table 3). Exposed patients had higher preperiod medical costs than controls.

Delirium or hallucinations occurred at a rate of 16.07 cases per 1000 person-years among exposed patients and 10.75 cases per 1000 person-years among controls (Table 4). However, the number of events (5 for exposed patients and 4 for controls) was too few to assess whether there were statistical differences between cohorts.

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