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Impact of a Comprehensive COPD Therapeutic Interchange Program on 30-Day Readmission Rates in Hospitalized Patients

Maren A. McGurran PharmD, BCPS
Lisa M. Richter PharmD, BCPS, BCCCP
Nathan D. Leedahl PharmD, BCPS
David D. Leedahl PharmD, BCPS-AQ ID, BCCCP

BACKGROUND

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States, and nearly 6.4% of Americans reported that they have been diagnosed with the disease.12 This number is likely an underestimate as a result of the more than 50% of adults with low pulmonary function who reported that they were not aware that they had COPD.3 The prevalence of COPD is expected to increase over the next 30 years because of the aging population.4 The direct economic costs attributable to COPD and asthma have been estimated at $53.7 billion, with the cost for prescription medicines at $20.4 billion and hospital inpatient stays at $13.1 billion.5

Pharmacological therapy for COPD is used to reduce symptoms, reduce the frequency and severity of exacerbations, and improve exercise tolerance and health status.6 According to the Global Initiative for Chronic Obstructive Lung Disease 2017 report, bronchodilators, anticholinergics, inhaled corticosteroids, and combination products are the mainstays for inhaled COPD pharmacological treatment.6 The choice within each class depends largely on multiple patient-specific factors, including availability, cost, delivery mechanism, clinical response, and side effects.6

There are over 20 inhaled medications approved by the Food and Drug Administration (FDA) that can be used for the pharmacological management of COPD. Because of the many different inhaler options, patients who are admitted to the hospital with a COPD diagnosis are maintained on various pharmacologic regimens to manage their disease outside the hospital. This creates a problem for inpatient pharmacies in maintaining a cost-effective inventory and for respiratory therapists or nurses in administering treatment with the appropriate technique.

Therapeutic interchange is defined by the American Society of Health-System Pharmacists as “an authorized exchange of therapeutic alternatives in accordance with previously established and approved written guidelines or protocols within a formulary system.”7 Interchanges can be used as a method of pharmaceutical cost management and are a way to standardize hospital therapy. They also offer one proposed way for managing the variety of different COPD inhalers that patients may present with on their home medication list.

What is unknown is how therapeutic interchange programs for COPD medications produce clinical effectiveness while also taking into account pharmacy costs. The aim of this study was to evaluate the clinical and financial impact of a CTIP in hospitalized patients with COPD.

METHODS

Study Design

The study groups consisted of two hospital systems within the same health care enterprise system. Our intervention group was admitted to a 550-bed tertiary hospital and managed with a pharmacist-led CTIP for inhaled products used in COPD, and our control group was admitted to a 545-bed tertiary care hospital, which did not have a CTIP in place. Our intervention group utilizes a pharmacist-led CTIP, approved by the local pharmacy and therapeutics (P&T) committee, for all known inhaled products used for COPD management during the study period (Table 1). These products will be interchanged at time of verification for one of the nine approved respiratory products. Our control group did not have CTIP for any inpatient medications. The study was approved by the institutional review board with a waiver of informed consent and HIPAA authorization, and was performed in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments.

Study Population

Electronic medical records were identified with the presence of COPD on diagnosis at time of discharge, as determined by International Classification of Diseases, 10th Revision (ICD-10) code starting with J44: J44.0 (COPD, with acute lower respiratory infection), J44.1 (COPD with acute exacerbation), or J44.9 (COPD, unspecified). COPD did not have to be the primary reason for admission. The intervention group had 1,350 patients and the control group had 1,535 patients included in the analysis. Patients under the age of 18 were excluded from analysis. Only the index hospitalization was included in the analysis, and subsequent readmissions were not included.

Data Collection

In addition to 30-day mortality, readmission rates, and pharmacy inhaler and nebulized-product costs, the following information was collected for each patient: length of stay, age, sex, payer, comorbidities, and case-mix index (CMI). The severity of illness was determined by the CMI. The charge report for the patient population included only inhalers and/or unit-dosed nebulized products that were administered. All pharmacy costs for inhalers and unit-dose nebulized products were determined by the average wholesale price (AWP) in June 2018. Only patients with pharmacy charges for inhalers and unit-dose nebulized products were included in the cost analysis. Baseline characteristics related to comorbidities were determined by ICD-10 codes associated with those conditions.

OUTCOMES

We performed a retrospective, cohort analysis from July 1, 2016 through June 30, 2017. The primary outcome was 30-day readmission rate. The secondary outcomes were 30-day mortality rates and pharmacy cost for inhaled products.

Statistical Analysis

Pearson’s Chi-squared tests were used for categorical variables. T-tests and Wilcoxon rank-sum tests were used for statistical analysis of parametric and non-parametric continuous variables, respectively. Data are percentages with the mean ± standard deviation (SD). Data were assessed by univariable analysis, with a P-value of ≤ 0.05 being considered as statistically significant. Data were analyzed with JMP software, version 12.2.0 (Cary, North Carolina).

RESULTS

We reviewed 2,885 patients’ index hospitalization with the presence of COPD diagnosis at time of discharge (1,350 in the intervention group and 1,535 in the control group). The acuity of these two hospital systems, as determined by fiscal year 17 average CMI, was 2 and 1.58 for our intervention and control groups, respectively. Baseline characteristics between the groups were similar; however, the intervention group had a statistically higher rate of asthma, depression, and hypertension, and a higher severity of illness, as illustrated by CMI (2.3 vs. 1.6; P = < 0.01). Overall, Medicare was the primary payer for both groups, but there were statistically significant differences in the primary payer between the two groups. The intervention group had a statistically significant, greater number of patients on Medicare (79% vs. 75.1%; P = 0.01) and Medicaid (8.5% vs. 5.9%; P = < 0.01), but the control group had a statistically significant, greater number of patients with private insurance (14.7% vs. 9.2%; P = < 0.01) and self-paid patients (1.3% vs. 0.4%; P = 0.01). A full summary of baseline characteristics can be found in Table 2.

Univariable analysis demonstrated that the patients in the intervention group, who utilized a CTIP, had a statistically significant, lower 30-day readmission rate (5.8% vs. 8.3%; P = 0.012). The difference in 30-day mortality was not statistically significant (Table 3). In the intervention group and the control group, 1,006 (75%) patients and 1,194 (78%) patients, respectively, received at least one inhaler and/or unit-dose nebulized products. The intervention group was statistically associated with a lower average pharmacy-inhaler cost per patient ($221 vs. $311; P = < 0.01). However, the intervention group was associated with a statistically significant, longer length of stay (6.2 days vs. 4.6 days; P = < 0.01). A full summary of clinical outcomes and pharmacy-inhaler and nebulized-product costs per patient can be found in Tables 3 and 4, respectively.

DISCUSSION

Therapeutic interchanges are implemented as a method for pharmaceutical cost management and a way to standardize therapy. There are no studies comparing patient outcomes and pharmacy costs in a facility with a CTIP for COPD inhalers with a facility that does not utilize formulary interchanges.

We noted a decreased rate of 30-day readmissions and decreased pharmacy-inhaled medication costs per patient in the intervention group. The control group had a decreased length of hospital stay, and no statistically significant difference in 30-day mortality was noted between the groups. Patients admitted in the two groups exhibited similar characteristics, with the exception that more patients had asthma, depression, hypertension, and a higher severity of illness in the intervention group. This is consistent with our intervention hospital system’s higher acuity during our study period.

Although there was a lower 30-day readmission rate in our intervention group, this may have been influenced by the longer length of stay. While we cannot exclude the possibility that the CTIP was responsible for the increased length of stay, there may have been other factors that affected the length of stay, such as the higher severity of illness found in our intervention group, issues with placement post-discharge, or other unmeasured confounding variables.

There are conflicting financial studies looking at the use of multidose inhalers (MDI) compared with nebulizers. One study found that pharmacy inhaler charges were lower when using MDI versus hand-held nebulizers.8 Another study found that there were savings in switching to nebulizer treatments from MDI.9 Neither of these studies evaluated patient outcomes. A study assessing the interchange of a combination of long-acting beta agonist (LABA)/long-acting muscarinic antagonist (LAMA) product for patients with COPD over a daily anticholinergic inhaler plus a twice-daily LABA, found that the interchange was not statistically associated with an increased 30-day readmission rate, but was associated with a lower cost of care.10

In addition to pharmacy costs, other aspects of health care are affected by formulary substitutions. In the intervention group, three primary inhalers were utilized (Figure 1) versus a more robust spread of inhalers in the control group (Figure 2). The three primary inhalers utilized in the intervention group were all once-daily inhalers. For the control group, two of the three most frequently dispensed inhalers are FDA-approved for twice-daily dosing. Using once-daily medications leads to fewer administrations needing to be delivered, and could save time. Moreover, doing so allows respiratory therapists or nurses to focus on the administration of these inhalers, instead of having to rotate through different inhaler types and administration techniques. A CTIP also could aid in inventory control. Being able to primarily use three inhalers allows for the acquisition of a smaller variety of inhalers, and avoids having to obtain inhalers from outside sources and having to label and identify the patient’s own inhalers for use inside the hospital.

The intervention group was associated with statistically fewer pharmacy costs for inhalers and unit-dose nebulized products. Another cost-saving measure, which was unaccounted for in this study and could come about through formulary substitution, is pharmacy reimbursements through rebates. This could lead to greater pharmacy department cost savings in some cases.

The results of this study may have some applicability to the therapeutic and financial effect of a CTIP on asthma patients. There is overlap with the inhaled and unit-dose medications. However, only 8.5% of our patient population had asthma, and additional research would need to be carried out to evaluate these effects. Furthermore, this study has internal validity, as demonstrated by the fact that the CTIP implemented by our intervention group did not harm patients and was associated with pharmacy cost savings. However, we cannot directly apply these findings to a CTIP that uses different inhaler interchanges.

There are several limitations to our study, which was conducted at a single health care system and was retrospective in nature. We relied on the use of ICD-10 codes for the diagnosis of COPD, as opposed to clinical diagnosis. An additional limitation is that patients’ discharge medication lists were not evaluated to see if patients were returned to their home inhaler. Although this limitation exists, the CTIP process at this health care system was to link the home and formulary-substituted products upon discharge. This provided transparency to the prescriber regarding what medication the patient was taking at home. Moreover, a previous study that looked at an automatic therapeutic substitution (ATS) at an academic center found that only 5% of patients were discharged on the ATS medication. 11 Lastly, pharmacy costs were calculated from the AWP in June 2018. We cannot exclude the possibility that varying charges for the same product existed at certain points in time during our study. Also, these pharmacy costs do not include potential rebates and group purchasing rates.

CONCLUSION

This study demonstrates that the use of a CTIP of COPD inhalers through an approved therapeutic interchange policy does not worsen patient outcomes and may provide pharmacy cost savings. The automatic therapeutic formulary substitution was statistically associated with a decreased 30-day readmission rate (5.8% vs. 8.3%; P = 0.012) and decreased pharmacy costs for inhalers and unit-dose nebulized products ($221 vs. $311; P = < 0.01), but also with an increased length of hospital stay (6.2 days vs. 4.6 days; P = < 0.01). Randomized prospective trials are needed to validate whether a CTIP of COPD inhalers is safe and cost-effective.

Figures and Tables

Intervention Group: Inhaler Distribution

Control Group: Inhaler Distribution

CTIP Inhaled Medications

Generic Brand Manufacturer Dosing Therapeutic Substitution
Generic, brand name, manufacturer, dosing
LAMA/LABA Combination Inhalers
Tiotropium bromide/olodaterol Stiolto Respimat Boehringer Ingelheim 2 inhalations once daily Umeclidinium/vilanterol, Anoro Ellipta, GlaxoSmithKline, 62.5/25 mcg: 1 inhalation once daily
Glycopyrrolate/formoterol fumarate Bevespi Aerosphere AstraZeneca 2 inhalations once daily
Indacaterol/glycopyrrolate Utibron Neohaler Sunovion 1 inhalation b.i.d.
ICS/LABA Combination Inhalers
Fluticasone propionate/salmeterol Advair HFA, Advair Diskus, Advair Airduo GlaxoSmithKline 45/21 mcg: 2 inhalations b.i.d.
55/14 mcg: 1 inhalation b.i.d.
100/50 mcg: 1 inhalation b.i.d.
115/21 mcg: 2 inhalations b.i.d.
113/14 mcg: 1 inhalation b.i.d.
250/50 mcg: 1 inhalation b.i.d.
Fluticasone furoate/vilanterol, Breo Ellipta, GlaxoSmithKline, 100/25 mcg: 1 inhalation once daily
Budesonide/formoterol Symbicort AstraZeneca 80/4.5 mcg: 2 inhalations b.i.d.
Mometasone/formoterol Dulera Merck 100/5 mcg: 2 inhalations b.i.d.
Fluticasone propionate/salmeterol Advair HFA, Advair Diskus, Advair Airduo GlaxoSmithKline 230/21 mcg: 2 inhalations b.i.d.
232/14 mcg: 1 inhalation b.i.d.
500/50 mcg: 1 inhalation b.i.d.
Fluticasone furoate/vilanterol, Breo Ellipta, GlaxoSmithKline, 200/25 mcg: 1 inhalation once daily
Budesonide/formoterol Symbicort AstraZeneca 160/4.5 mcg: 2 inhalations b.i.d.
Mometasone/formoterol Dulera Merck 200/5 mcg: 2 inhalations b.i.d.
LAMA Inhalers
Tiotropium Spiriva Respimat Boehringer Ingelheim 2.5 mcg: 2 inhalations once daily Umeclidinium, Incruse Ellipta, GlaxoSmithKline, 62.5 mcg: 1 inhalation once daily
Tiotropium Spiriva Handihaler Boehringer Ingelheim 18 mcg: 1 inhalation once daily
Aclidinium Tudorza Pressair AstraZeneca 400 mcg: 1 inhalation b.i.d.
Glycopyrrolate Seebri Neohaler Sunovion 15.6 mcg: 1 inhalation b.i.d.
LABA Inhalers
Salmeterol Serevent Diskus GlaxoSmithKline 50 mcg Formoterol nebulization, Mylan, 20 mcg, same frequency as Serevent Diskus
Arformoterol Brovana Sunovion 15 mcg Formoterol nebulization, Mylan, 20 mcg, same frequency as Brovana
Indacaterol Arcapta Neohaler Sunovion 75 mcg: 1 inhalation once daily Formoterol nebulization, Mylan, 20 mcg: 1 nebulization b.i.d.
Olodaterol Striverdi Respimat Boehringer Ingelheim 2.5 mcg: 2 inhalations once daily Formoterol nebulization, Mylan, 20 mcg: 1 nebulization b.i.d.
SABA Inhalers
Albuterol ProAir HFA Teva 90 mcg: 2 inhalations every 4–6 hours Albuterol nebulization, Nephron, 2.5 mg/3 mL, same frequency as albuterol inhaler
Proventil HFA Merck
Ventolin HFA GlaxoSmithKline
Levalbuterol Xopenex HFA Sunovion 45 mcg: 2 inhalations every 4–6 hours as needed Levalbuterol nebulization, Teva, 1.25 mg, same frequency as Xopenex
ICS Inhalers
Beclomethasone QVAR Redihaler Teva 80–240 mcg/day Budesonide nebulization, Nephron, 0.25 mg: 1 nebulization 1–2 times/day
241–480 mcg/day Budesonide nebulization, Nephron, 0.5 mg: 1 nebulization b.i.d.
> 481 mcg/day Budesonide nebulization, Nephron, 1 mg: 1 nebulization b.i.d.
Budesonide Pulmicort AstraZeneca 180–600 mcg/day Budesonide nebulization, Nephron, 0.25 mg: 1 nebulization 1–2 times/day
601–1,200 mcg/day Budesonide nebulization, Nephron, 0.5 mg: 1 nebulization b.i.d.
> 1,201 mcg/day Budesonide nebulization, Nephron, 1 mg: 1 nebulization b.i.d.
Ciclesonide Alvesco Colvis 160 mcg/day Budesonide nebulization, Nephron, 0.25 mg: 1 nebulization 1–2 times/day
320 mcg/day Budesonide nebulization, Nephron, 0.5 mg: 1 nebulization b.i.d.
640 mcg/day Budesonide nebulization, Nephron, 1 mg: 1 nebulization b.i.d.
Fluticasone Flovent GlaxoSmithKline 88–264 mcg/day Budesonide nebulization, Nephron, 0.25 mg: 1 nebulization 1–2 times/day
265–660 mcg/day Budesonide nebulization, Nephron, 0.5 mg: 1 nebulization b.i.d.
> 661 mcg/day Budesonide nebulization, Nephron, 1 mg: 1 nebulization b.i.d.
Mometasone Asmanex Merck = 200 mcg/day Budesonide nebulization, Nephron, 0.25 mg: 1 nebulization 1–2 times/day
220–440 mcg/day Budesonide nebulization, Nephron, 0.5 mg: 1 nebulization b.i.d.
> 440 mcg/day Budesonide nebulization, Nephron, 1 mg: 1 nebulization b.i.d.
SABA/SAMA Combination Inhalers
Albuterol/ipratropium Combivent Respimat Boehringer Ingelheim 2.5/0.5 mg: 1 inhalation four times daily Albuterol/ipratropium nebulization, Nephron, 3/0.5 mg, same frequency as Combivent Respimat
SAMA Inhalers
Ipratropium Atrovent HFA Boehringer Ingelheim 17 mcg: 2 inhalations four times daily Ipratropium nebulization, Nephron, 500 mcg, same frequency as Atrovent HFA

Abbreviations: b.i.d.: twice daily; mcg: microgram; mg: milligram; ICS: inhaled corticosteroid; LABA: long-acting beta agonist; LAMA: long-acting muscarinic antagonist; SABA: short-acting beta agonist; SAMA: short-acting muscarinic antagonist

Characteristics of Patients Discharged With the Presence of COPD Diagnosis

Intervention (n = 1,350) Control (n = 1,535) P value
Male, n (%) 708 (52) 824 (54) 0.52
Female, n (%) 642 (48) 711 (46)
Age (years ± SD) 71 ± 11.2 70 ± 11.8 0.18
Case-mix index (score ± SD) 2.3 ± 0.73 1.6 ± 0.43 < 0.01
Comorbid conditions
 Asthma (%) 9.7 7.4 0.03
 CKD (%) 16.3 17.9 0.26
 Depression (%) 20.1 12.4 < 0.01
 Diabetes Mellitus (%) 23.9 23.4 0.76
 Heart Failure (%) 22.9 22.9 1.0
 Hypertension (%) 48.1 41.2 < 0.01
 Ischemic Heart Disease (%) 25.5 23.1 0.14
Insurance type
 Medicaid (%) 8.5 5.9 < 0.01
 Medicare (%) 79.0 75.1 0.01
 Private (%) 9.2 14.7 < 0.01
 Self (%) 0.4 1.3 0.01
 Veterans a_airs (%) 2.8 2.9 0.85

CKD: chronic kidney disease; COPD: chronic obstructive pulmonary disease; SD: standard deviation

Association of Formulary Substitution With Clinical Outcomes

Intervention (n = 1,350) Control (n = 1,535) P value
30-day readmission rates (%) 5.8 8.3 0.012
30-day mortality (%) 9.9 8.4 0.17
Hospital length of stay (days ± SD) 6.2 ± 9.2 4.6 ± 4.5 < 0.01

SD: standard deviation

Pharmacy Inhaler and Nebulized Products Cost

Intervention (n = 1,006) Control (n = 1,194) P value
Pharmacy cost for inhalers and unit-dose nebulized products per patient ($ ± SD) 221 ± 380 311 ± 352 < 0.01

SD: standard deviation; $: U.S. dollar

Author bio: 
Dr. McGurran is a PGY2 pharmacy resident at Parkland Health & Hospital System in Dallas, Texas. Dr. N. Leedahl is the Lead Pharmacist for Sanford Health Enterprise Pharmacy in Fargo, North Dakota. Dr. D. Leedahl is a Clinical Pharmacy Manager for Sanford Medical Center in Fargo, North Dakota and a Clinical Investigator with Sanford Research in Sioux Falls, South Dakota. Dr. Richter is the Director of Experiential Outreach and Assessment and Assistant Professor of Practice at North Dakota State University in Fargo.

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