Payer formulary tier increases of apixaban: how patients respond and potential implications.

OBJECTIVE: To assess potential impacts of formulary tier increases of apixaban-an efficacious oral anticoagulant (OAC) for preventing stroke in patients with atrial fibrillation (AF)-on patients' prescription drug plan (PDP) switching and OAC treatment patterns. METHODS: Nationwide claims data for Medicare beneficiaries with Parts A, B, and D (100% sample) were used to assess apixaban-treated AF patients who faced a formulary tier increase for apixaban in 2017 by their Part D PDP. Patients' out-of-pocket (OOP) costs for apixaban were described, along with PDP switching and OAC treatment patterns. RESULTS: Among 1845 included patients, 97.7% had apixaban on tier 3 of their plan's formulary in 2016 and faced its increase to tier 4 for 2017. Approximately 4% (N = 81) of patients pre-emptively switched to a different PDP for 2017 with almost all switching to plans with apixaban on a lower formulary tier and 85.2% continuing apixaban treatment. Among the 96% (N = 1764) of patients who remained on the same PDP for 2017, over half (57.5%) continued apixaban treatment, despite increased OOP costs ($54 vs. $135 for a 30-day supply in 2016 vs. 2017). Only 12.4% of those who remained on the same plan for 2017 switched to another OAC, while as much as 30.1% discontinued OACs. These discontinuers exhibited higher comorbidity burdens than patients continuing on any OAC. CONCLUSION: The majority of patients continued on apixaban despite higher OOP cost, suggesting patients' reluctance to change treatment for non-medical reasons; however, 30% of patients discontinued OAC treatment after higher apixaban tier placement.

Trends and factors associated with outpatient anticoagulant treatment initiation among VTE patients with active cancer.

BACKGROUND: Patients with venous thromboembolism (VTE) and cancer are at higher risk of recurrent VTE and mortality. Clinical guidelines recommend anticoagulant treatment for these patients. This study assessed trends in outpatient anticoagulant treatment and factors associated with this treatment initiation in outpatient setting among this high-risk patient population. OBJECTIVE: To study trends and factors associated with anticoagulant treatment initiation among patients with VTE and cancer. METHODS: VTE cancer patients age ≥65 were identified from the SEER-Medicare database from 01JAN2014-31DEC2019. Patients were enrolled for ≥6 months prior to their first VTE (i.e. index event) and without evidence of other reasons for anticoagulation (i.e., atrial fibrillation). Patients were also required to be enrolled for ≥30 days after index. Cancer status was identified from SEER or Medicare database in the 6 months pre- through 30 days post-VTE. Patients were classified into treated or untreated cohorts depending on whether they initiated outpatient anticoagulant treatment within 30 days post-index. The trends of treated vs. untreated were evaluated by quarter. Logistic regression was used to identify demographic-, VTE-, cancer- and comorbid-related factors associated with anticoagulant treatment initiation. RESULTS: A total of 28,468 VTE-cancer patients met all study criteria. Of these, ~46 % initiated outpatient anticoagulant treatment within 30 days, and ~54 % did not. The above rates were stable from 2014 to 2019. Factors such as VTE diagnosis in inpatient setting, pulmonary embolism (PE) diagnosis, and pancreatic cancer were associated with increased odds whereas bleeding history and some comorbid factors were associated with decreased odds of initiating anticoagulant treatment. CONCLUSION: Over half of VTE patients with cancer did not initiate outpatient anticoagulant treatment within the first 30-days after VTE diagnosis. This trend was stable from 2014 to 2019. A range of cancer-, VTE-, and comorbid-related factors were associated with the likelihood of the treatment initiation.

Effectiveness and Safety of Direct Oral Anticoagulants Among Patients with Non-valvular Atrial Fibrillation and Multimorbidity.

INTRODUCTION: In the USA, there is a steady rise of atrial fibrillation due to the aging population with increased morbidity. This study evaluated the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) among elderly patients with non-valvular atrial fibrillation (NVAF) and multimorbidity prescribed direct oral anticoagulants (DOACs). METHODS: Using the CMS Medicare database, a retrospective observational study of adult patients with NVAF and multimorbidity who initiated apixaban, dabigatran, or rivaroxaban from January 1, 2012 to December 31, 2017 was conducted. High multimorbidity was classified as having ≥ 6 comorbidities. Cox proportional hazard models were used to evaluate the hazard ratios of S/SE and MB among three 1:1 propensity score matched DOAC cohorts. All-cause healthcare costs were estimated using generalized linear models. RESULTS: Overall 36% of the NVAF study population had high multimorbidity, forming three propensity score matched (PSM) cohorts: 12,511 apixaban-dabigatran, 60,287 apixaban-rivaroxaban, and 12,567 dabigatran-rivaroxaban patients. Apixaban was associated with a lower risk of stroke/SE and MB when compared with dabigatran and rivaroxaban. Dabigatran had a lower risk of stroke/SE and a similar risk of MB when compared with rivaroxaban. Compared to rivaroxaban, apixaban patients incurred lower all-cause healthcare costs, and dabigatran patients incurred similar all-cause healthcare costs. Compared to dabigatran, apixaban patients incurred similar all-cause healthcare costs. CONCLUSION: Patients with NVAF and ≥ 6 comorbid conditions had significantly different risks for stroke/SE and MB when comparing DOACs to DOACs, and different healthcare expenses. This study's results may be useful for evaluating the risk-benefit ratio of DOAC use in patients with NVAF and multimorbidity.

Effectiveness and safety of apixaban vs warfarin among venous thromboembolism patients at high-risk of bleeding.

This study evaluated effectiveness and safety of apixaban versus warfarin among venous thromboembolism patients at high-risk of bleeding (defined as having at least one of the following bleeding risk factors: ≥75 years; used antiplatelet, NSAIDs, or corticosteroids; had prior gastrointestinal bleeding or gastrointestinal-related conditions; late stage chronic kidney disease). Adult venous thromboembolism patients initiating apixaban or warfarin with ≥1 bleeding risk factor were identified from Medicare and four commercial claims databases in the United States. To balance characteristics between apixaban and warfarin patients, stabilized inverse probability treatment weighting was conducted. Cox proportional hazards models were used to estimate the risk of recurrent venous thromboembolism, major bleeding, and clinically relevant non-major bleeding. In total, 88,281 patients were identified. After inverse probability treatment weighting, the baseline patient characteristics were well-balanced between the two cohorts. Among venous thromboembolism patients at high-risk of bleeding, apixaban was associated with significantly lower risk of recurrent venous thromboembolism, major bleeding and clinically relevant non-major bleeding. No significant interactions were observed between treatment and number of risk factors on major bleeding and clinically relevant non-major bleeding or between treatment and type of bleeding risk factors on any of the outcomes. In conclusion, apixaban was associated with significantly lower risk of recurrent venous thromboembolism and bleeding among venous thromboembolism patients at high-risk of bleeding. Effects were generally consistent across subgroups of patients with different number or type of bleeding risk factors.

Non-persistence to Oral Anticoagulation Treatment in Patients with Non-valvular Atrial Fibrillation in the USA.

BACKGROUND: Studies have shown that patients with non-valvular atrial fibrillation (NVAF) who discontinue oral anticoagulants (OACs) are at higher risk of complications such as stroke. OBJECTIVE: This analysis compared the risk of non-persistence with OACs among patients with NVAF. METHODS: Adult patients with NVAF who initiated apixaban, dabigatran, rivaroxaban, or warfarin were identified using 01JAN2013-30JUN2019 data from Centers for Medicare and Medicaid Services and four US commercial claims databases. Non-persistence was defined as discontinuation (no evidence of index OAC use for ≥ 60 days from the last days' supply) or switch to another OAC. Kaplan-Meier curves were generated to illustrate time to non-persistence along with cumulative incidences of non-persistence. Baseline and time-varying covariates were evaluated, and adjusted Cox proportional hazards models were used to evaluate non-persistence risk. RESULTS: In total, 363,823 patients receiving apixaban, 57,121 receiving dabigatran, 282,831 receiving rivaroxaban, and 317,337 receiving warfarin were included. Of these, 47-72% discontinued/switched OAC therapy within an average 9-month follow-up. Apixaban was associated with a lower risk of non-persistence than were dabigatran (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.61-0.62), rivaroxaban (HR 0.76; 95% CI 0.75-0.76), and warfarin (HR 0.74; 95% CI 0.74-0.75). Dabigatran was associated with a higher risk of non-persistence than were warfarin (HR 1.21; 95% CI 1.19-1.22) and rivaroxaban (HR 1.23; 95% CI 1.22-1.25), and rivaroxaban was associated with a lower risk of non-persistence than was warfarin (HR 0.98; 95% CI 0.97-0.98). Clinical events (stroke/systemic embolism and major bleeding [MB]) during follow-up were predictors of non-persistence (stroke HR 1.57; 95% CI 1.53-1.61; MB HR 2.96; 95% CI 2.92-3.00). CONCLUSION: In over one million patients with NVAF, our results suggest differences in anticoagulation treatment persistence across OAC agents, even after accounting for clinical events after OAC initiation. It is important for clinicians and patients to take these differences into consideration, especially as non-persistence to OAC therapy is associated with thromboembolic complications.

Effectiveness and Safety of Apixaban Versus Warfarin in Obese Patients with Nonvalvular Atrial Fibrillation Enrolled in Medicare and Veteran Affairs.

Real-world studies have evaluated the use of anticoagulants in obese patients with nonvalvular atrial fibrillation (NVAF), but they have been limited by sample size or the use of diagnosis codes on claims to define obesity. This retrospective study used body weight data of ≥100 kg or a body mass index of ≥30 kg/m2 to identify elderly (aged ≥65 years) NVAF patients with obesity in dually enrolled Veterans Affairs and fee-for-service Medicare patients. It evaluated the risk of stroke/systemic embolism (SE) and major bleeding (MB) in patients that initiated apixaban versus warfarin. Stabilized inverse probability treatment weighting was used to balance the baseline characteristics between patients prescribed apixaban and warfarin in obese patients. Cox models were used to evaluate the relative risk of stroke/SE and MB. Overall, 35.9% (n = 26,522) of the NVAF population were obese, of which 13,604 apixaban and 12,918 warfarin patients were included. After inverse probability treatment weighting, patient characteristics were balanced. The mean age was 75 years, the mean CHA2DS2-VASc score (Congestive Heart Failure, Hypertension, Age ≥75 [Doubled], Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack [Doubled], Vascular Disease, Age 65-74, Female) was 3.8, the mean HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) Score was ∼2.6, and >98% of patients were males. Obese apixaban patients were associated with a similar risk of stroke/SE (hazard ratio: 0.82; 95% confidence interval: 0.66 to 1.03) and a significantly lower risk of MB (hazard ratio: 0.62; 95% confidence interval: 0.54 to 0.70) versus warfarin. No significant interaction was observed between treatment and obesity status (nonobese, obese/nonmorbid, obese/morbid) for stroke/SE (interaction p = 0.602) or MB (interaction p = 0.385). In obese patients with NVAF, apixaban was associated with a similar risk of stroke/SE and a significantly lower risk of MB versus warfarin.

Effectiveness and Safety of Apixaban Versus Warfarin Among Older Patients with Venous Thromboembolism with Different Demographics and Socioeconomic Status.

INTRODUCTION: Impact of demographics and socioeconomic status (SES) on anticoagulant treatment outcomes among patients with venous thromboembolism (VTE) is not well understood. This study evaluated risks of recurrent VTE, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB) among older patients with VTE initiating apixaban or warfarin stratified by demographics and SES. METHODS: Adult patients (≥ 65 years) who initiated apixaban or warfarin after a VTE event were selected from the US CMS Medicare database (September 2014-December 2017). Stabilized inverse probability treatment weighting (IPTW) was used to balance patient characteristics between treatment cohorts. Patients were stratified by age, gender, race, and SES. For each subgroup, Cox proportional hazard models were used to evaluate if there was a significant interaction (p < 0.10) between treatment and subgroup for recurrent VTE, MB, and CRNMB. RESULTS: In total, 22,135 apixaban and 45,840 warfarin patients with VTE were included. Post-IPTW, patient characteristics were balanced between treatment cohorts. In older patients, apixaban treatment was associated with significantly lower risks of recurrent VTE (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.52-0.79), MB (HR 0.65; 95% CI 0.57-0.75), and CRNMB (HR 0.79; 95% CI 0.75-0.85) versus warfarin. When stratified by demographics and SES, higher incidence rates of recurrent VTE, MB, and CRNMB were observed for black vs white patients and patients with lower vs higher SES. Comparison of apixaban with warfarin by different demographic and SES subgroups showed generally consistent results as the overall analysis. For most subgroups, no significant interaction was observed between treatment and subgroup strata for recurrent VTE, MB, and CRNMB. CONCLUSION: Among older patients with VTE initiating apixaban or warfarin, higher rates of recurrent VTE and bleeding were observed in black patients and patients with lower SES. Apixaban had a lower risk of recurrent VTE, MB, and CRNMB compared to warfarin. Analyses of demographic and SES subgroups showed consistent findings.

Effectiveness and safety of oral anticoagulants among non-valvular atrial fibrillation patients with polypharmacy.

AIMS: Polypharmacy is prevalent among non-valvular atrial fibrillation (NVAF) patients and presents a potential issue for the effective management of NVAF. This study compared the risk of stroke/systemic embolism (SE) and major bleeding (MB) among NVAF patients with polypharmacy newly prescribed oral anticoagulants (OACs). METHODS AND RESULTS: A retrospective study of NVAF patients with polypharmacy who initiated OACs from 01 January 2013 to 30 September 2015 was conducted using US CMS Medicare and four commercial databases. Polypharmacy was defined as ≥6 concomitant medications on the index date. Propensity score matching was conducted to compare non-vitamin K antagonists OACs (NOACs) to warfarin as well as between NOACs. Cox proportional hazard models were used to evaluate the risk of stroke/SE and MB. A total of 188 893 patients with polypharmacy were included, with an average of 8 concomitant medications (interquartile range 6-9). Compared to warfarin, apixaban [hazard ratio (HR): 0.59, 95% confidence interval (CI): 0.52-0.68], and rivaroxaban (HR: 0.75, 95% CI: 0.69-0.83) were associated with a lower risk of stroke/SE. Apixaban (HR: 0.57, 95% CI: 0.54-0.61) and dabigatran (HR: 0.76, 95% CI: 0.66-0.88) were associated with a decreased risk of MB compared with warfarin. Compared with dabigatran and rivaroxaban, apixaban was associated with a lower risk of stroke/SE and MB. Dabigatran was associated with lower risk of MB compared with rivaroxaban. CONCLUSIONS: In this observational study of anticoagulated NVAF patients with polypharmacy, effectiveness and safety profiles are more favourable for NOACs vs. warfarin. Our observations are hypothesis generating and may help inform future clinical trials regarding appropriate OAC treatment selection in polypharmacy patients.

Utilization of anticoagulants and predictors of treatment among hospitalized patients with atrial fibrillation in the USA.

OBJECTIVE: To evaluate utilization of anticoagulants (ACs) and the predictors of treatment of patients with a diagnosis of atrial fibrillation (AF) during a hospital stay in the USA. METHODS: Patients (≥18 years of age) who had a primary or secondary discharge diagnosis code of AF during a hospitalization (without a diagnosis of venous thromboembolism) were identified from the Premier Hospital database (1 January 2016-30 September 2017). AC treatments were examined during hospitalizations to assign AF patients into 3 study cohorts: those who received an oral AC (OAC), those who received parenteral AC only, and those who did not receive AC therapy. Multivariable logistic regression analyses were carried out to evaluate potential predictors of receiving parenteral AC only vs. OAC therapy, no AC therapy vs. OAC therapy, as well as the specific OAC drug choices. RESULTS: Of the patients hospitalized with an AF diagnosis (n = 482,729; mean age: 74.7 years; 46.8% female; 82.9% White; 79.4% with Medicare), 42.6% received OAC therapy (most commonly, warfarin or apixaban), 35.3% parenteral AC only, and 22.2% no AC therapy. A key predictor of not receiving OAC therapy was having an AF diagnosis in the second position (applicable to 87.4% of study population). Greater comorbidity level and prior baseline bleeding were strong predictors of receiving parenteral AC only or not receiving any AC therapy vs. receiving OAC therapy. Predictors of receiving warfarin vs. apixaban included higher stroke risk and prior baseline bleeding. LIMITATIONS: OAC utilization may have been underestimated since outpatient OAC utilization was not included in the analysis. CONCLUSIONS: A substantial portion of hospitalized AF patients did not receive any AC therapy, particularly those patients with an AF diagnosis in the second position on hospital records. The predictors of inpatient AC treatment that were identified may be helpful in the clinical decision-making process for patients who are hospitalized with AF.

Comparisons between Oral Anticoagulants among Older Nonvalvular Atrial Fibrillation Patients.

OBJECTIVES: Older adult patients are underrepresented in clinical trials comparing non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin. This subgroup analysis of the ARISTOPHANES study used multiple data sources to compare the risk of stroke/systemic embolism (SE) and major bleeding (MB) among very old patients with nonvalvular atrial fibrillation (NVAF) prescribed NOACs or warfarin. DESIGN: Retrospective observational study. SETTING: The Centers for Medicare & Medicaid Services and three US commercial claims databases. PARTICIPANTS: A total of 88 582 very old (aged ≥80 y) NVAF patients newly initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, to September 30, 2015. MEASUREMENTS: In each database, six 1:1 propensity score matched (PSM) cohorts were created for each drug comparison. Patient cohorts were pooled from all four databases after PSM. Cox proportional hazards models were used to estimate hazard ratios (HRs) of stroke/SE and MB. RESULTS: The patients in the six matched cohorts had a mean follow-up time of 7 to 9 months. Compared with warfarin, apixaban (HR = .58; 95% confidence interval [CI] = .49-.69), dabigatran (HR = .77; 95% CI = .60-.99), and rivaroxaban (HR = .74; 95% CI = .65-.85) were associated with lower risks of stroke/SE. For MB, apixaban (HR = .60; 95% CI = .54-.67) was associated with a lower risk; dabigatran (HR = .92; 95% CI = .78-1.07) was associated with a similar risk, and rivaroxaban (HR = 1.16; 95% CI = 1.07-1.24) was associated with a higher risk compared with warfarin. Apixaban was associated with a lower risk of stroke/SE and MB compared with dabigatran (stroke/SE: HR = .65; 95% CI = .47-.89; MB: HR = .60; 95% CI = .49-.73) and rivaroxaban (stroke/SE: HR = .72; 95% CI = .59-.86; MB: HR = .50; 95% CI = .45-.55). Dabigatran was associated with a lower risk of MB (HR = .77; 95% CI = .67-.90) compared with rivaroxaban. CONCLUSION: Among very old NVAF patients, NOACs were associated with lower rates of stroke/SE and varying rates of MB compared with warfarin. J Am Geriatr Soc 67:1662-1671, 2019.

Continuation with apixaban treatment is associated with lower risk for hospitalization and medical costs among elderly patients.

Objective: To compare the risk of hospitalization and costs associated with major bleeding (MB) or stroke/systemic embolism (SE) among elderly patients with nonvalvular atrial fibrillation (NVAF) who initiated apixaban then switched to another oral anticoagulant (OAC) vs. those who continued with apixaban treatment. Methods: NVAF patients (≥65 years) initiating apixaban were identified from the Humana database (1 January 2013-30 September 2017) and grouped into switcher and continuer cohorts. For switchers, the earliest switch from apixaban to another OAC was defined as the index event/date. A random date during apixaban treatment was selected as the index date for continuers. Patients were followed from index date to health plan disenrollment or 31 December 2017, whichever was earlier. Multivariable regression analyses were used to examine the association of switchers vs. continuers with risk of MB-related or stroke/SE-related hospitalization and healthcare costs during follow-up. Results: Of 7858 elderly NVAF patients included in the study, 14% (N = 1110; mean age: 78 years) were switchers; 86% (N = 6748; mean age: 79 years) were continuers. Apixaban switchers vs. continuers had significantly greater risk of MB-related hospitalization (hazard ratio [HR]: 2.00; 95% CI: 1.52-2.64; p < .001) during follow-up; risk of stroke/SE hospitalization did not differ significantly (HR: 1.36, 95% CI: 0.89-2.06, p = .154). MB- and stroke/SE-related medical costs were higher for switchers vs. continuers, although total all-cause healthcare costs were similar. Conclusion: Elderly patients with NVAF in the US who continued with apixaban treatment had a lower risk of MB-related hospitalization and lower MB- and stroke/SE-related medical costs compared to patients who switched to another OAC.

Impact of comorbid conditions in COPD patients on health care resource utilization and costs in a predominantly Medicare population.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often have multiple underlying comorbidities, which may lead to increased health care resource utilization (HCRU) and costs. OBJECTIVE: To describe the comorbidity profiles of COPD patients and examine the associations between the presence of comorbidities and HCRU or health care costs. METHODS: A retrospective cohort study utilizing data from a large US national health plan with a predominantly Medicare population was conducted. COPD patients aged 40-89 years and continuously enrolled for 12 months prior to and 24 months after the first COPD diagnosis during the period of January 01, 2009, through December 31, 2010, were selected. Eleven comorbidities of interest were identified 12 months prior through 12 months after COPD diagnosis. All-cause and COPD-related hospitalizations and costs were assessed 24 months after diagnosis, and the associations with comorbidities were determined using multivariate statistical models. RESULTS: Ninety-two percent of 52,643 COPD patients identified had at least one of the 11 comorbidities. Congestive heart failure (CHF), coronary artery disease, and cerebrovascular disease (CVA) had the strongest associations with all-cause hospitalizations (mean ratio: 1.56, 1.32, and 1.30, respectively; P<0.0001); other comorbidities examined had moderate associations. CHF, anxiety, and sleep apnea had the strongest associations with COPD-related hospitalizations (mean ratio: 2.01, 1.32, and 1.21, respectively; P<0.0001); other comorbidities examined (except chronic kidney disease [CKD], obesity, and osteoarthritis) had moderate associations. All comorbidities assessed (except obesity and CKD) were associated with higher all-cause costs (mean ratio range: 1.07-1.54, P<0.0001). CHF, sleep apnea, anxiety, and osteoporosis were associated with higher COPD-related costs (mean ratio range: 1.08-1.67, P<0.0001), while CVA, CKD, obesity, osteoarthritis, and type 2 diabetes were associated with lower COPD-related costs. CONCLUSION: This study confirms that specific comorbidities among COPD patients add significant burden with higher HCRU and costs compared to patients without these comorbidities. Payers may use this information to develop tailored therapeutic interventions for improved management of patients with specific comorbidities.

Association between adherence to medications for COPD and medications for other chronic conditions in COPD patients.

BACKGROUND: Patients with COPD often have multiple comorbidities requiring use of multiple medications, and adherence rates for maintenance COPD (mCOPD) medications are already known to be suboptimal. Presence of comorbidities in COPD patients, and use of medications used to treat those comorbidities (non-COPD medications), may have an adverse impact on adherence to mCOPD medications. OBJECTIVE: The objective of the study was to evaluate the association between non-adherence to mCOPD medications and non-COPD medications in COPD patients. METHODS: COPD patients were identified using a large administrative claims database. Selected patients were 40-89 years old and continuously enrolled for 12 months prior to and 24 months after the first identified COPD diagnosis (index date) during January 1, 2009 to December 31, 2010. Patients were required to have ≥1 prescription for a mCOPD medication within 365 days of the index date and ≥1 prescription for one of 12 non-COPD medication classes within ±30 days of the first COPD prescription. Adherence (proportion of days covered [PDC]) was measured during 365 days following the first COPD prescription. The association between non-adherence (PDC <0.8) to mCOPD and non-adherence to non-COPD medications was determined using logistic regression, controlling for baseline patient characteristics. RESULTS: A total of 14,117 patients, with a mean age of 69.9 years, met study criteria. Of these, 40.9% were males and 79.2% were non-adherent to mCOPD medications with a mean PDC of 0.47. Non-adherence to mCOPD medications was associated with non-adherence to 10 of 12 non-COPD medication classes (odds ratio 1.38-1.78, all P<0.01). CONCLUSION: Adherence to mCOPD medications is low. Non-adherence (or adherence) to mCOPD medications is positively related to non-adherence (or adherence) to non-COPD medications, implying that the need to take medications prescribed for comorbid conditions does not adversely impact adherence to mCOPD medications.

Development and Validation of a Predictive Model to Identify Individuals Likely to Have Undiagnosed Chronic Obstructive Pulmonary Disease Using an Administrative Claims Database.

BACKGROUND: Despite the importance of early detection, delayed diagnosis of chronic obstructive pulmonary disease (COPD) is relatively common. Approximately 12 million people in the United States have undiagnosed COPD. Diagnosis of COPD is essential for the timely implementation of interventions, such as smoking cessation programs, drug therapies, and pulmonary rehabilitation, which are aimed at improving outcomes and slowing disease progression. OBJECTIVE: To develop and validate a predictive model to identify patients likely to have undiagnosed COPD using administrative claims data. METHODS: A predictive model was developed and validated utilizing a retro-spective cohort of patients with and without a COPD diagnosis (cases and controls), aged 40-89, with a minimum of 24 months of continuous health plan enrollment (Medicare Advantage Prescription Drug [MAPD] and commercial plans), and identified between January 1, 2009, and December 31, 2012, using Humana's claims database. Stratified random sampling based on plan type (commercial or MAPD) and index year was performed to ensure that cases and controls had a similar distribution of these variables. Cases and controls were compared to identify demographic, clinical, and health care resource utilization (HCRU) characteristics associated with a COPD diagnosis. Stepwise logistic regression (SLR), neural networking, and decision trees were used to develop a series of models. The models were trained, validated, and tested on randomly partitioned subsets of the sample (Training, Validation, and Test data subsets). Measures used to evaluate and compare the models included area under the curve (AUC); index of the receiver operating characteristics (ROC) curve; sensitivity, specificity, positive predictive value (PPV); and negative predictive value (NPV). The optimal model was selected based on AUC index on the Test data subset. RESULTS: A total of 50,880 cases and 50,880 controls were included, with MAPD patients comprising 92% of the study population. Compared with controls, cases had a statistically significantly higher comorbidity burden and HCRU (including hospitalizations, emergency room visits, and medical procedures). The optimal predictive model was generated using SLR, which included 34 variables that were statistically significantly associated with a COPD diagnosis. After adjusting for covariates, anticholinergic bronchodilators (OR = 3.336) and tobacco cessation counseling (OR = 2.871) were found to have a large influence on the model. The final predictive model had an AUC of 0.754, sensitivity of 60%, specificity of 78%, PPV of 73%, and an NPV of 66%. CONCLUSIONS: This claims-based predictive model provides an acceptable level of accuracy in identifying patients likely to have undiagnosed COPD in a large national health plan. Identification of patients with undiagnosed COPD may enable timely management and lead to improved health outcomes and reduced COPD-related health care expenditures.

COPD exacerbation frequency and its association with health care resource utilization and costs.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) exacerbations account for a substantial proportion of COPD-related costs. OBJECTIVE: To describe COPD exacerbation patterns and assess the association between exacerbation frequency and health care resource utilization (HCRU) and costs in patients with COPD in a Medicare population. METHODS: A retrospective cohort study utilizing data from a large US national health plan was conducted including patients with a COPD diagnosis during January 1, 2007 to December 31, 2012, aged 40-89 years and continuously enrolled in a Medicare Advantage Prescription Drug plan. Exacerbation frequency, HCRU, and costs were assessed during a 24-month period following the first COPD diagnosis (follow-up period). Four cohorts were created based on exacerbation frequency (zero, one, two, and ≥three). HCRU and costs were compared among the four cohorts using chi-square tests and analysis of variance, respectively. A trend analysis was performed to assess the association between exacerbation frequency and costs using generalized linear models. RESULTS: Of the included 52,459 patients, 44.3% had at least one exacerbation; 26.3%, 9.5%, and 8.5% had one, two, and ≥three exacerbations in the 24-month follow-up period, respectively. HCRU was significantly different among cohorts (all P<0.001). In patients with zero, one, two, and ≥three exacerbations, the percentages of patients experiencing all-cause hospitalizations were 49.7%, 66.4%, 69.7%, and 77.8%, respectively, and those experiencing COPD-related hospitalizations were 0%, 40.4%, 48.1%, and 60.5%, respectively. Mean all-cause total costs (medical and pharmacy) were more than twofold greater in patients with ≥three exacerbations compared to patients with zero exacerbations ($27,133 vs $56,033; P<0.001), whereas a greater than sevenfold difference was observed in mean COPD-related total costs ($1,605 vs $12,257; P<0.001). CONCLUSION: COPD patients frequently experience exacerbations. Increasing exacerbation frequency is associated with a multiplicative increase in all-cause and COPD-related costs. This underscores the importance of identifying COPD patients at risk of having frequent exacerbations for appropriate disease management.

Factors associated with inpatient readmission among managed care enrollees with COPD.

OBJECTIVE: To assess factors associated with inpatient readmission among a US managed care population with chronic obstructive pulmonary disease (COPD). BACKGROUND: COPD is often accompanied by intermittent acute exacerbations, which may result in hospitalizations. These exacerbations are often associated with an increased frequency of subsequent exacerbations, which may lead to inpatient readmissions. METHODS: We assessed US managed care claims data for enrollees≥40 years old with an inpatient admission with a primary diagnosis of COPD (ICD-9-CM codes 491.xx, 492.xx or 496.xx) between 1 January 2010 and 31 December 2013 (discharge date of first observed inpatient admission defined the "index date"). Patients were required to be continuously enrolled for ≥12 months before the index date. Two non-mutually exclusive cohorts were analyzed: (1) patients with ≥30 days of post-index date continuous enrollment (to evaluate 30-day readmission) and (2) patients with ≥90 days of post-index date continuous enrollment (to evaluate 90-day readmission). Logistic regression evaluated the association between patient characteristics and risk of 30- and 90-day COPD-related and all-cause readmission. RESULTS: After applying selection criteria, 140,981 patients had ≥30 days of enrollment post-index date, and 123,545 patients had ≥90 days of enrollment post-index date. Within 30 days, nearly 20% of patients had an all-cause readmission and 7% had a COPD-related readmission. Within 90 days, 28% had an all-cause readmission and 12% had a COPD-related readmission. Logistic regression indicated that longer length of stay, older age, greater comorbidity burden, specific comorbidities and COPD complexity were associated with significantly greater odds of COPD-related 30- and 90-day readmission. Results for all-cause readmission were generally similar. CONCLUSIONS: Many of the factors associated with inpatient readmission documented here can be ascertained at discharge and may be used to inform discharge plans, with the end goal of improving patient outcomes, including reducing the risk of readmission.

Clinical and economic burden of COPD in a medicaid population.

OBJECTIVE: To evaluate the clinical and economic burden of COPD patients to Medicaid. STUDY DESIGN: Retrospective, observational matched cohort design. METHODS: We calculated the incremental costs incurred and medical resources used by COPD patients relative to those without COPD. Data were obtained from 8 Medicaid states during 2003-2007. COPD patients were defined as Medicaid beneficiaries ≥40 years with a COPD diagnosis (ICD-9 CM: 491.xx, 492.xx, 496.xx) and treated with maintenance drugs for COPD. Patients were matched (1:3) to Medicaid beneficiaries without a COPD diagnosis on age, gender, race, index year, Medicare/Medicaid dual eligibility, and use of long-term care. Results were stratified by Medicare/Medicaid dual eligibility status and race. RESULTS: A total of 10,221 COPD and 30,663 non-COPD patients were included. Cohorts were on average 65 years of age, 80% White, and 64.8% having Medicare/Medicaid dual eligibility. Inpatient hospitalizations and home healthcare visits/durable medical equipment were primary drivers of incremental medical costs. COPD patients were more than twice as likely to have a hospitalization (odds ratio [95% confidence interval] = 2.32 [2.19, 2.45]) or home healthcare visit/durable medical equipment (2.95 [2.82, 3.08]) compared to non-COPD patients. Medicaid incurred $2118/year in incremental costs due to COPD. On average, incremental costs were 7 times greater for non-dual-eligible patients ($4917) compared to dual-eligible patients ($667), and were more than double for Blacks compared to Whites ($4141 vs $1593). CONCLUSION: COPD imposes a substantial economic and clinical burden on the Medicaid program; this burden differs by dual eligibility status and race.

Short-acting ß-agonist use and its ability to predict future asthma-related outcomes.

BACKGROUND: Short-acting ß-agonist (SABA) use is well established in predicting asthma events in adults. However, this predictive ability has yet to be established in a pediatric population together with an assessment of amount of use. OBJECTIVE: To identify the number of SABA canisters that best predicts future asthma-related exacerbations and the optimal length of time for measurement of SABA use in pediatric and adult asthma patients. METHODS: Asthma patients were identified from a Medicaid and a commercially insured database (January 1, 2004, through December 31, 2005, and January 1, 2004, through June 30, 2006, respectively). Following the date of first asthma medication, an assessment period (3, 6, or 12 months) was used to measure SABA use. Asthma-related exacerbations were identified in the subsequent 12-month period. Receiver operating characteristic curve analyses and logistic regression were used to select the critical values of SABA use and optimal assessment periods and to conduct incremental analysis, respectively. RESULTS: A total of 33,793 Medicaid and 101,437 commercial patients met the study criteria. Use of 3 or more SABA canisters during 12 months was identified in both pediatric Medicaid and commercial populations to best predict an increased risk of an asthma-related exacerbation. For adults, use of 2 or more SABA canisters was found as the critical value with shorter optimal assessment periods of 3 and 6 months. Each additional SABA canister resulted in an 8% to 14% and 14% to 18% increase in risk of an asthma-related exacerbation in children and adults, respectively. CONCLUSION: The study identified critical values of SABA use that predict future asthma events. Each additional SABA canister predicted increases in exacerbation risk in children and adults.

Outcomes associated with timing of maintenance treatment for COPD exacerbation.

OBJECTIVES: To examine the impact of timing of maintenance treatment initiation (early vs delayed) on risk of future exacerbations and costs in chronic obstructive pulmonary disease (COPD) patients. STUDY DESIGN: Retrospective cohort design using data (January 1, 2003, through June 30, 2009) from a large, US-based integrated pharmacy and medical claims database. METHODS: Administrative claims from January 1, 2003, through June 30, 2009, were used. Methotrexate (MTx)-naïve patients (aged >40 years) with at least 1 COPD-related hospitalization/emergency department (ED) visit were included (discharge date was index date). Patients initiating MTx within the first 30 days and 31 to 180 days post-index were classified into early and delayed cohorts, respectively. Clinical and economic outcomes related to COPD exacerbations were assessed for 1 year post-index and compared between cohorts using regression models controlling for baseline characteristics. The incremental effect on outcomes of every 30-day delay in MTx initiation up to 6 months after the index event was also assessed. RESULTS: The majority of the 3806 patients (78.6%) received early MTx. A significantly higher proportion of patients in the delayed cohort had a COPD-related hospitalization/ED visit compared with the early cohort (25.6% vs 18.0%; P <.001). After controlling for baseline differences, the delayed cohort had a 43% (P <.001) higher risk of a future COPD-related hospitalization/ED visit compared with the early cohort. Every 30-day delay was associated with 9% risk increase (P = .002). Treatment delay also increased COPD-related costs ($5012 vs $3585; P <.001). CONCLUSION: Early MTx initiation is associated with reduced risk of future COPD exacerbations and lower costs.