Frequency of hospital readmissions for venous thromboembolism and associated hospital costs and length of stay among acute medically ill patients in the US.

Objectives: This study evaluated the frequency of hospital readmissions for venous thromboembolism (VTE) and the associated costs and length of stay (LOS) among acute medically ill patients in the US using a real-world claims database analysis. Methods: Patients (≥40 years of age) at risk of VTE due to hospitalization for acute medical illnesses, based on primary hospital discharge diagnosis codes, were identified from the MarketScan databases between July 1, 2011 and March 31, 2015. Patients were required to have continuous insurance enrollment in the 6 months prior to initial (index) hospitalizations (baseline period) and in the 6 months after hospital discharge (follow-up period). The proportions of patients with VTE-related (diagnosis at any position) and VTE as primary diagnosis hospital readmissions during the follow-up period were evaluated. The associated costs and LOS for such readmissions were also determined, as well as time to VTE-related readmissions. Results: Of the study population (n = 12,785; mean age = 68.3 years), most were hospitalized primarily for infectious diseases (35.2%), followed by respiratory diseases (27.9%), cancer (15.7%), heart failure (11.8%), ischemic stroke (8.1%), and rheumatic diseases (1.4%). Of the overall study population, 2.1% (n = 268) had a VTE-related hospital readmission in the 6 months following discharge of their index hospitalization, of which 36.6% (n = 98) were for a primary diagnosis of VTE. Approximately 25.4% of the VTE-related hospital readmissions occurred within the first 30 days of discharge and 58.2% within 90 days. The mean cost for a hospital readmission with a primary diagnosis of VTE was $18,681 (mean LOS = 5.0 days); for readmissions with a primary diagnosis of DVT and PE, mean costs were $14,719 and $23,305, respectively. Conclusions: Among this study population of patients hospitalized for acute medical illnesses, some experienced a VTE event requiring re-hospitalization, with 25% occurring within the first 30 days after hospital discharge.

Venous Thromboembolism Prophylaxis and Risk for Acutely Medically Ill Patients Stratified by Different Ages and Renal Disease Status.

The objectives of this study were to examine venous thromboembolism (VTE) prophylaxis patterns and risk for VTE events during hospitalization and in the outpatient continuum of care among patients hospitalized for acute illnesses in the United States with stratification by different age groups and renal disease status. Acutely ill hospitalized patients were identified from the MarketScan databases (January 1, 2012-June 30, 2015) and grouped by age (<65, 65-74, ≥75 years old) and whether or not they had a baseline diagnosis of renal disease, separately. Of acutely ill hospitalized patients, 60.1% (n = 10 748) were <65 years old, 15.7% (n = 2803) were 65 to 74 years old, and 24.3% (n = 4344) were ≥75 years old; 32.9% (n = 5892) had baseline renal disease. Among the study cohorts, the majority of patients received no VTE prophylaxis regardless of age or baseline renal status (52.1%-63.6%). Rates of VTE during hospitalization and in the 6 months postdischarge were 4.7%, 4.6%, and 4.5% for patients <65, 65 to 74, and ≥75 years old, respectively, and 6.3% and 3.8% for patients with and without baseline renal disease. The risk for VTE was elevated for 30 to 40 days after index admission regardless of age and renal disease status.

Influence of the duration of hospital length of stay on frequency of prophylaxis and risk for venous thromboembolism among patients hospitalized for acute medical illnesses in the USA.

BACKGROUND: We evaluated whether the duration of hospital stay influences venous thromboembolism (VTE) prophylaxis patterns and VTE risk during hospitalization and post-discharge among patients hospitalized for acute illnesses in the USA. METHODS: Patients hospitalized for acute illnesses were identified from the US MarketScan Commercial and Medicare databases (January 1, 2012-June 30, 2015). Patients were stratified by index hospital length of stay (LOS), with study groups with 1-3 day, 4-6 day, and ≥7 day LOSs. Use of VTE prophylaxis and VTE event rates during and after hospitalization (6-month follow-up) were evaluated. RESULTS: Of the overall population, 8647 had a 1-3 day LOS, 5551 had a 4-6 day LOS, and 3697 had a ≥7 day LOS. A greater proportion of patients with a 1-3 day LOS (66.2%) did not receive any VTE prophylaxis in comparison to patients with a 4-6 day LOS (55.0%) and ≥7 day LOS (48.8%; p<0.001). Proportions of patients with VTE events during the index hospitalization increased with longer hospital LOS (1-3 day LOS: 0.5%; 4-6 day LOS: 1.3%; ≥7 day LOS: 5.4%), as did proportions of patients with VTE events during the 6-month follow-up (1-3 day LOS: 2.4%; 4-6 day LOS: 2.7%; ≥7 day LOS: 4.2%). CONCLUSION: Among this study population of hospitalized acutely ill patients in the USA, VTE pharmacologic prophylaxis was underutilized, regardless of the duration of hospital stay. However, the risk for VTE events was substantial, with nearly 10% of those with a ≥7 day LOS having suffered a VTE event within 6 months.

Economic Burden of Treatment-Resistant Depression Among Patients Hospitalized for Major Depressive Disorder in the United States.

Objectives: This study aimed to evaluate hospital length of stay (LOS) and cost as well as readmission risk and the associated economic burden among patients hospitalized for treatment-resistant and non-treatment-resistant major depressive disorder. Methods: Adult patients with a primary hospital discharge diagnosis of major depressive disorder were identified from the Premier Hospital Database (January 1, 2012-September 30, 2015). Patients were stratified into two cohorts: those whose hospital treatment was suggestive of treatment-resistant depression and those with non-treatment-resistant depression. Hospital LOS and cost during the initial admission and readmissions rates, LOS, and cost within the 6-month follow-up were compared between cohorts with a propensity score-matched sample. Results: After matching, 45,066 patients were included in each cohort. For index hospitalizations, mean hospital LOS was longer (7.4 vs. 5.9 days, p<0.001) and mean hospital cost higher ($8,681 vs. $6,632, p<0.001) for patients with treatment-resistant depression vs. non-treatment-resistant depression. Rates for all-cause (24.4% vs. 20.0%, p<0.001), major depressive disorder-related (17.0% vs. 13.3%, p<0.001), and suicidal ideation/suicide attempt-related (12.8% vs. 9.5%, p<0.001) readmissions were higher for patients with treatment-resistant depression. Mean LOS and total hospital costs per patient for readmissions were also greater for patients with treatment-resistant depression vs. non-treatment-resistant depression. Correspondingly, the combined hospital cost (index hospitalization+all-cause readmissions) was greater for patients with treatment-resistant depression ($12,370 vs. $9,429, p<0.001). Conclusions: Treatment-resistant depression was associated with substantial economic burden among patients hospitalized for major depressive disorder. More-effective treatment and care for this patient population may reduce the hospital burden of patients with treatment-resistant depression.

Impact of earlier versus later monitoring on disease progression and healthcare costs among patients with chronic myeloid leukemia in the United States.

We evaluated the impact of molecular monitoring earlier as compared to later in the course of chronic myeloid leukemia (CML) on disease progression and healthcare costs in the real-world setting in the US. Patients with a diagnosis of CML were identified from the MarketScan claims databases (1 January 2006 to 30 June 2016). Multivariable regression analyses were used to control for differences in patient cohorts with earlier versus later monitoring. Of the 2730 CML patients in the study population, 60% (n = 1633) received earlier monitoring and 40% (n = 1097) received later monitoring only. After adjusting for differences in patient characteristics, patients with earlier monitoring had a lower likelihood of CML progression during the follow-up period (odds ratio: 0.72, confidence interval: 0.53-0.96; p = .03) and lower total healthcare costs ($6794 versus $9782 per-patient-per-month, p < .001) than patients with later monitoring. Patients who are monitored earlier in the course of CML may have better outcomes and lower total costs of care.

Venous Thromboembolism Prophylaxis and Risk in the Inpatient and Outpatient Continuum of Care Among Hospitalized Acutely Ill Patients in the US: A Retrospective Analysis.

INTRODUCTION: Venous thromboembolism (VTE) is a leading cause of preventable morbidity and mortality among hospitalized patients in the US. The objectives of this study were to examine VTE prophylaxis patterns and risk for VTE events during hospitalization and post-discharge among patients hospitalized for acute illnesses in the US. METHODS: Acutely ill hospitalized patients were identified from the MarketScan databases (January 1, 2012-June 30, 2015). Proportions of patients that received inpatient and/or outpatient VTE prophylaxis were determined. VTE rates were calculated for the overall study population and for each subpopulation with each acute illness type. Risk for VTE events after the index admission was determined by Kaplan-Meier analysis. RESULTS: Of the acutely ill patients (n = 17,895, mean age: 58.4 years), most were hospitalized for infectious diseases (40.6%), followed by respiratory diseases (31.0%), cancer (10.7%), heart failure (10.4%), ischemic stroke (6.4%), and rheumatic diseases (0.9%). Among the entire study population, 59.1% did not receive any VTE prophylaxis, and only 7.1% received both inpatient and outpatient prophylaxis. Among the overall study population, cumulative VTE rate, including during index admission and within 6 months post-discharge, was 4.6%. VTE risk in the inpatient and outpatient continuum of care remained elevated up to 30-40 days after hospital admission, with 60.1% of VTEs occurring within 40 days of hospital admission. CONCLUSION: In this retrospective analysis of nearly 18,000 patients hospitalized for acute illnesses, 59.1% did not receive any VTE prophylaxis and only 7.1% received VTE prophylaxis in both the inpatient and outpatient continuum of care, despite significant VTE risk extending from hospitalization into the post-discharge period. FUNDING: Portola Pharmaceuticals.

Comparison of Drug Switching and Discontinuation Rates in Patients with Nonvalvular Atrial Fibrillation Treated with Direct Oral Anticoagulants in the United States.

INTRODUCTION: Continuous usage of direct oral anticoagulants (DOACs) among nonvalvular atrial fibrillation (NVAF) patients is essential to maintain stroke prevention. We examined switching and discontinuation rates for the three most frequently initiated DOACs in NVAF patients in the USA. METHODS: Patients who initiated apixaban, rivaroxaban, or dabigatran (index event/date) were identified from the Pharmetrics Plus claims database (Jan 1, 2013-Sep 30, 2016, includes patients with commercial and Medicare coverage) and grouped into cohorts by index DOAC. Patients were required to have a diagnosis of NVAF and continuous health plan enrollment for 12 months prior to the index date (baseline period) and at least 3 months during the follow-up period. Drug switching rates to any other DOAC or warfarin and index DOAC discontinuation rate were evaluated separately with descriptive statistics, Kaplan-Meier analysis, and multivariable Cox regression analysis. RESULTS: Of the NVAF study population (n = 41,864), 37% initiated apixaban (n = 15,352; mean age 62 years), 51% initiated rivaroxaban (n = 21,250; mean age 61 years), and 13% initiated dabigatran (n = 5262; mean age 61 years). During the follow-up period, the unadjusted drug switching rates of patients treated with apixaban, rivaroxaban, and dabigatran were 3.6%, 6.3%, and 11.1%, respectively (p < 0.001 across the three cohorts); while the index DOAC discontinuation rates were 52.8%, 60.3%, and 62.9%, respectively (p < 0.001). After we controlled for differences in patient characteristics, patients treated with rivaroxaban (HR 1.8; 95% CI 1.6-2.0; p < 0.001) and dabigatran (HR 3.4; 95% CI 3.0-3.8, p < 0.001) had a significantly greater likelihood for drug switching than patients treated with apixaban. Also, both rivaroxaban (HR 1.1; 95% CI 1.1-1.2, p < 0.001) and dabigatran (HR 1.3; 95% CI 1.2-1.3, p < 0.001) treated patients were more likely to discontinue treatment. CONCLUSION: In the real-world setting, patients with NVAF newly treated with apixaban were less likely to switch or discontinue treatment compared to patients treated with rivaroxaban or dabigatran. FUNDING: Pfizer and Bristol-Myers Squibb.

Hospital Resource Utilization and Costs Associated With Warfarin Versus Apixaban Treatment Among Patients Hospitalized for Venous Thromboembolism in the United States.

A real-world US database analysis was conducted to evaluate the hospital resource utilization and costs of patients hospitalized for venous thromboembolism (VTE) treated with warfarin versus apixaban. Additionally, 1-month readmissions were evaluated. Of 28 612 patients with VTE identified from the Premier Hospital database (August 2014-May 2016), 91% (N = 26 088) received warfarin and 9% (N = 2524) received apixaban. Outcomes were assessed after controlling for key patient/hospital characteristics. For index hospitalizations, the average length of stay (LOS) was longer (3.8 vs 3.1 days, P < .001; difference: 0.7 days) and mean hospitalization cost higher (US$3224 vs US$2,740, P < .001; difference: US$484) for warfarin versus apixaban-treated patients. During the 1-month follow-up period, warfarin treatment was associated with a greater risk of all-cause readmission (odds ratio [OR]: 1.27; 95% confidence interval [CI]: 1.09-1.48, P = .003), major bleeding (MB)-related readmission (OR: 2.10; 95% CI: 1.03-4.27, P = .04), and any bleeding-related readmission (OR: 1.67; 95% CI: 1.09-2.56, P = .02) versus apixaban. The results of this real-world analysis show that compared to warfarin, apixaban treatment was associated with shorter index hospital stays, lower index hospitalization costs, and reduced risk of MB-related readmissions among hospitalized patients with VTE.

Economic value of regular monitoring of response to treatment among US patients with chronic myeloid leukemia based on an economic model.

BACKGROUND: Regular molecular monitoring with reverse-transcription quantitative PCR (RT-qPCR) analysis of BCR-ABL1 transcripts is associated with reduced disease progression among patients with chronic myeloid leukemia (CML). Molecular monitoring assists in the timely detection of primary or secondary resistance to tyrosine kinase inhibitor (TKI) therapy and is a recommended practice by the National Comprehensive Cancer Network guidelines. An economic model was developed to estimate the potential impact of CML monitoring vs lack of monitoring on patient healthcare costs. METHODS: An Excel-based decision-analytic economic model was developed from a US payer perspective. The model was used to estimate the expected healthcare cost differences between regular molecular monitoring of CML patients and lack of monitoring. CML progression rates among patients with vs without monitoring, the annual cost of CML progression, the average number of monitoring tests per year, and the average cost per RT-qPCR monitoring test were incorporated into the model. Univariate and multivariable sensitivity analyses were conducted. RESULTS: Based on estimates in published literature, disease progression to the accelerated/blast phase occurs among 0.35% of patients with monitoring and 5.12% of patients without monitoring, and the annual cost of CML progression is $136,308 per patient year. The analysis found that total healthcare costs, including the costs associated with CML progression and RT-qPCR monitoring tests (three tests per year), were $1,142 for patients with monitoring and $6,982 for patients without monitoring (difference = $5,840). In a hypothetical cohort of 100 patients with CML, achieving a 100% monitoring rate was associated with a total cost-savings of $584,005 compared to a 0% monitoring rate. This cost-savings remained consistent under both univariate and multivariable sensitivity analyses. CONCLUSION: Regular CML monitoring was associated with improved outcomes among CML patients and, consequently, reduced healthcare costs.

Comparison of the cost-effectiveness of biologic drugs used for moderate-to-severe psoriasis treatment in the United States.

PURPOSE: To compare the cost-effectiveness of the newly approved biologic drug, brodalumab, with other commonly used biologics for the treatment of moderate-to-severe psoriasis in the United States. METHODS: An economic model was constructed in Excel to compare average costs to achieve Psoriasis Area and Severity Index (PASI) 75, 90 and 100 among moderate-to-severe psoriasis patients treated with biologics. Total annual costs to health plans associated with treatment with five different biologics were estimated and cost-effectiveness compared using the estimated average cost per PASI 75, PASI 90 and PASI 100. RESULTS: Total annual costs to a health plan per patient with adalimumab, brodalumab, ixekizumab, secukinumab and ustekinumab were estimated at $51,246, $38,538, $65,484, $57,510 and $57,013. Mean annual treatment costs per PASI 75, 90 and 100 were the lowest for brodalumab, with the annual cost per PASI 75 for brodalumab, adalimumab, ixekizumab, secukinumab and ustekinumab estimated at $48,782, $82,655, $77,957, $75,671 and $87,243, per PASI 90 at $51,383, $119,178, $94,904, $108,509 and $130,615, and per PASI 100 at $87,585, $284,702, $176,983, $205,393, and $366,645. CONCLUSIONS: Brodalumab, which had the lowest drug cost and high drug efficacy, was associated with the lowest cost per PASI 75, 90 and 100 among the biologics evaluated.

The budget impact of brodalumab for the treatment of moderate-to-severe plaque psoriasis on US commercial health plans.

INTRODUCTION: Brodalumab is a new biologic approved by the US Food and Drug Administration in 2017 for the treatment of moderate-severe psoriasis. This study evaluated the impact of the introduction of brodalumab on the pharmacy budget on US commercial health plans. METHODS: An Excel-based health economic decision analytic model with a US health plan perspective was developed. The model incorporated published moderate-to-severe psoriasis prevalence data; market shares of common biologic drugs, including adalimumab, ustekinumab, secukinumab, ixekizumab, and etanercept, used for the treatment of moderate-severe psoriasis; 2017-year Wholesale Acquisition Costs for the biologic drugs; drug dispensing fee; patient co-pay; and drug contracting discount. Total annual health plan costs for the biologic drugs were estimated. Scenarios with different proportions of patients treated with brodalumab were compared to a control scenario when no brodalumab was used. RESULTS: In a hypothetical commercial health plan covering two million members, 7,038 moderate-to-severe psoriasis patients were estimated to be eligible for treatment with brodalumab. Prior to brodalumab approval, the proportions of patients treated by other biologics were estimated at 50.8% for adalimumab, 13.5% for ustekinumab, 14.1% for secukinumab, 4.4% for ixekizumab, and 17.2% for etanercept. With a 20% drug price discount applied to all biologics, the annual health plan costs for brodalumab, adalimumab, ustekinumab, secukinumab, ixekizumab, and etanercept were estimated at $37,224, $49,166, $55,084, $56,061, $64,396, and $57,170, respectively. When no brodalumab is used, the total annual pharmacy budget for the biologics used among these patients was estimated at $414,362,647. Among scenarios where the proportions of brodalumab usage were 3%, 8%, 16%, and 30%, the total annual pharmacy cost was estimated to be reduced by $3,698,129, $9,861,677, $19,723,355, and $36,981,290, respectively. CONCLUSION: Based on the economic model, brodalumab has the potential to substantially reduce pharmacy expenditures for the treatment of patients with moderate-to-severe plaque psoriasis in the US.

All-Cause, Stroke/Systemic Embolism-, and Major Bleeding-Related Health-Care Costs Among Elderly Patients With Nonvalvular Atrial Fibrillation Treated With Oral Anticoagulants.

In this study, all-cause, stroke/systemic embolism (SE)-related, and major bleeding (MB)-related health-care costs among elderly patients with nonvalvular atrial fibrillation (NVAF) initiating treatment with different oral anticoagulants (OACs) were compared. Patients ≥65 years of age initiating OACs, including apixaban, rivaroxaban, dabigatran, and warfarin, were identified from the Humana Research Database between January 1, 2013, and September 30, 2015. Propensity score matching was used to separately match the different OAC cohorts with the apixaban cohort. All-cause health-care costs and stroke/SE-related and MB-related medical costs per patient per month (PPPM) were compared using generalized linear or 2-part regression models. Compared to apixaban, rivaroxaban was associated with significantly higher all-cause health-care costs (US$2234 vs US$1846 PPPM, P < .001) and MB-related medical costs (US$106 vs US$47 PPPM, P < .001), dabigatran was associated with significantly higher all-cause health-care costs (US$1980 vs US$1801 PPPM, P = .007), and warfarin was associated with significantly higher all-cause health-care costs (US$2386 vs US$1929 PPPM, P < .001), stroke/SE-related medical costs (US$42 vs US$18 PPPM, P < .001), and MB-related medical costs (US$132 vs US$51 PPPM, P < .001). Among elderly patients with NVAF, other OACs were associated with higher all-cause health-care costs than apixaban.

Impact of Warfarin Persistence on Health-Care Utilization and Costs Among Patients With Atrial Fibrillation Managed in Anticoagulation Clinics in the United States.

Warfarin is a recommended therapy to reduce the risk of stroke in patients with nonvalvular atrial fibrillation (NVAF). The objectives of this study were to identify potential factors associated with warfarin persistence and evaluate the impact of warfarin persistence on health-care resource utilization and costs among patients with NVAF in the United States. Patients (≥18 years) with ≥1 inpatient or ≥2 outpatient diagnoses of AF without valvular disease were identified from an electronic medical record database (January 1, 2004, to January 31, 2015). The patients with NVAF were grouped into 2 cohorts-persistent with warfarin therapy and not persistent (warfarin discontinuation in <365 days). A multivariable regression was used to identify potential predictors of warfarin persistence. Health-care costs were evaluated during a 12-month follow-up period for study cohorts. Among the study population, 52%, (n = 4086) were persistent with warfarin therapy and 48% (n = 3722) were not. Patients with NVAF with higher Charlson comorbidity index and CHADS2 scores versus those with scores of 0 were more likely to demonstrate persistence with warfarin therapy. After adjusting for patient characteristics, patients with NVAF persistent with warfarin therapy versus those who were not were 30% less likely to be hospitalized during the follow-up period ( P < .001). Additionally, total all-cause health-care costs (US $2183, P < .001) and stroke-related costs (US $788, P < .001) were significantly lower among patients persistent with warfarin therapy versus those who were not. Patients with NVAF who have greater comorbidity and stroke risk are more likely to be persistent with warfarin therapy. Patients with NVAF who are persistent with warfarin therapy versus those who are not have lower all-cause and stroke-related health-care costs.

Effect of Apixaban Versus Warfarin Use on Health Care Resource Utilization and Costs Among Elderly Patients with Nonvalvular Atrial Fibrillation.

BACKGROUND: The clinical trial ARISTOTLE showed that apixaban was superior to warfarin in reducing the risks of stroke and bleeding among patients with nonvalvular atrial fibrillation (NVAF). Further study of the effect of apixaban versus warfarin use on health care resource utilization (HCRU) and associated costs in the real-world setting is warranted, especially among elderly patients who are at higher risk of stroke and bleeding. OBJECTIVE: To compare HCRU and costs among elderly NVAF patients treated with apixaban versus warfarin in the United States. METHODS: Elderly patients (aged ≥ 65 years) with Medicare coverage who initiated apixaban or warfarin were identified from the Humana research database during January 1, 2013-September 30, 2015. Patients were required to have 12 months of continuous insurance coverage before drug initiation (baseline period) and an atrial fibrillation diagnosis during the baseline period or on the date of drug initiation. NVAF patients were grouped into cohorts depending on the drug initiated. Propensity score matching (PSM) was conducted to control for differences in demographics and clinical characteristics of study cohorts. Patients were followed after the index date for a variable length of follow-up. All-cause and disease-specific HCRU and costs during the follow-up were evaluated before and after PSM and reported as per patient per year. RESULTS: Of the overall (unmatched) population, 8,250 patients (mean age: 78.0 years) initiated apixaban and 14,051 patients (mean age: 78.2 years) initiated warfarin. Among NVAF patients who initiated apixaban versus those who initiated warfarin, mean Charlson Comorbidity Index (CCI) scores (3.0 vs. 3.4, P < 0.001); stroke risk scores, including CHADS2 (2.7 vs. 2.9, P < 0.001) and CHA2DS2-VASc (4.6 vs. 4.7, P < 0.001); and bleeding risk scores, including HAS-BLED (3.1 vs. 3.2, P < 0.001), were lower. Additionally, total annual all-cause health care costs were lower during the baseline period for patients treated with apixaban versus warfarin ($17,077 vs. $20,236, P < 0.001). After PSM, 14,214 patients were matched, with 7,107 in each cohort. Mean age, CCI score, and stroke and bleeding risks were similar between matched cohorts, as were total all-cause health care costs during the baseline period. During the follow-up among matched cohorts, apixaban versus warfarin treatment was associated with higher annual pharmacy costs ($5,159 vs. $2,867, P < 0.001) but lower annual inpatient ($8,327 vs. $14,296, P < 0.001), outpatient ($9,655 vs. $11,469, P < 0.001), and total all-cause health care costs ($23,141 vs. $28,633, P < 0.001), which were reflective of lower inpatient, outpatient, and all-cause HCRU among apixaban-treated patients. Furthermore, bleeding-related ($2,101 vs. $3,963, P < 0.001) and stroke-related ($652 vs. $1,178, P = 0.001) annual medical costs were lower for patients treated with apixaban versus warfarin. CONCLUSIONS: After controlling for differences in patient characteristics, in the real-world setting apixaban versus warfarin use was associated with less HCRU and lower total all-cause health care costs and costs for bleeding- and stroke-related medical services, but greater pharmacy costs, among elderly NVAF patients. DISCLOSURES: This study was sponsored by Pfizer and Bristol-Myers Squibb. Deitelzweig is a consultant for Pfizer and Bristol-Myers Squibb and has served on their advisory boards and received speaker fees. Deitelzweig also serves as consultant and advisory board member to Portola and Janssen. Luo, Trocio, and Mardekian are employees of Pfizer and own stock in the company. Gupta and Curtice are employees of Bristol-Myers Squibb and own stock in the company. Lingohr-Smith, Menges, and Lin are employees of Novosys Health, which received research funds from Pfizer and Bristol-Myers Squibb to conduct this study and develop the manuscript. Study concept and design were primarily contributed by Deitelzweig, Luo, and Gupta, along with Trocio, Mardekian, Curtice, and Lin. Lin, Menges, and Lingohr-Smith took the lead in data collection, with assistance from the other authors. Data interpretation was performed by Deitelzweig, Menges, and Lin, with assistance from the other authors. The manuscript was written by Lingohr-Smith and Menges, along with the other authors, and revised by all the authors. Some aspects of this study were presented at the American Heart Association Scientific Sessions in New Orleans, Louisiana, November 12-16, 2016.

Comparison of effectiveness and safety of treatment with apixaban vs. other oral anticoagulants among elderly nonvalvular atrial fibrillation patients.

OBJECTIVE: To compare the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) of elderly (≥65 years of age) nonvalvular atrial fibrillation (NVAF) patients initiating apixaban vs. rivaroxaban, dabigatran, or warfarin. METHODS: NVAF patients with Medicare Advantage coverage in the US initiating oral anticoagulants (OACs, index event) were identified from the Humana database (1 January 2013-30 September 2015) and grouped into cohorts depending on OAC initiated. Propensity score matching (PSM), 1:1, was conducted among patients treated with apixaban vs. each other OAC, separately. Rates of S/SE and MB were evaluated in the follow-up. Cox regressions were used to compare the risk of S/SE and MB between apixaban and each of the other OACs during the follow-up. RESULTS: The matched pairs of apixaban vs. rivaroxaban (n = 13,620), apixaban vs. dabigatran (n = 4654), and apixaban vs. warfarin (n = 14,214) were well balanced for key patient characteristics. Adjusted risks for S/SE (hazard ratio [HR] vs. rivaroxaban: 0.72, p = .003; vs. warfarin: 0.65, p < .001) and MB (HR vs. rivaroxaban: 0.49, p < .001; vs. warfarin: 0.53, p < .001) were significantly lower during the follow-up for patients treated with apixaban vs. rivaroxaban and warfarin. Adjusted risks for S/SE (HR: 0.78, p = .27) and MB (HR: 0.82, p = .23) of NVAF patients treated with apixaban vs. dabigatran trended to be lower, but did not reach statistical significance. CONCLUSIONS: In the real-world setting after controlling for differences in patient characteristics, apixaban is associated with significantly lower risk of S/SE and MB than rivaroxaban and warfarin, and a trend towards better outcomes vs. dabigatran among elderly NVAF patients in the US.

Incremental economic burden associated with major bleeding among atrial fibrillation patients treated with factor Xa inhibitors.

OBJECTIVE: To evaluate healthcare resource use and costs incurred during, as well as following hospitalization for major bleeding (MB), among atrial fibrillation (AF) patients treated with factor Xa inhibitors Methods: Patients with an AF diagnosis and MB hospitalization (index event) were identified from the MarketScan Commercial and Medicare databases (January 1, 2011-December 31, 2014). Patients were required to have ≥1 prescription for rivaroxaban or apixaban within 3 months prior to MB hospitalization. AF patients treated with Xa inhibitors, but who did not have any diagnosis of MB during the study period were identified. Hospital resource use and costs were evaluated for index MB hospitalizations. Healthcare resource use and associated costs were also evaluated for up to 12 months and compared between AF patients with and without MB. RESULTS: Of the overall patient population with AF treated with factor Xa inhibitors (n = 92,949), 3,081 (3.3%) were identified as patients with MB and 89,868 without MB. The mean hospital length of stay and hospital cost for index MB hospitalizations were 5.3 days and $28,059, respectively. Total all-cause healthcare costs were higher during the 12 months of follow-up for AF patients with MB vs without ($63,866 vs $37,916, p < .001). After adjusting for differences in patient characteristics, mean total healthcare costs were estimated at $58,169 for patients with MB vs $41,241 for patients without MB. LIMITATIONS: Since this was an observational study using a claims database analysis, a causal relationship between factor Xa inhibitor treatment and MB events cannot be inferred from the results of this study. CONCLUSION: In the real-world setting, the cost of initial hospitalizations for MB was substantial, and the incremental burden of total healthcare costs within 1 year following MB hospitalization was high. Approaches to better manage the continuum of care of AF patients with factor Xa inhibitor-associated MB may reduce the healthcare economic burden.

Evaluation of healthcare resource utilization and incremental economic burden of patients with chronic myeloid leukemia after disease progression to blast phase.

AIMS: To evaluate healthcare resource utilization and economic burden of patients with chronic myeloid leukemia (CML) progression to the blast phase. METHODS: Patients (≥ 18 years) with ≥1 inpatient or ≥2 outpatient CML diagnoses were identified from the MarketScan Commercial and Medicare databases (January 1, 2007-June 30, 2015). CML patients were grouped into two study cohorts, those with evidence of disease progression to the blast phase and those without. Patients were required to have continuous medical and prescription coverage during a 12-month baseline period, in which demographics and clinical characteristics were evaluated. All-cause healthcare resource utilization and costs were evaluated during the baseline period, and a variable follow-up period, lasting ≥1 day and up to 1 year. Generalized linear models (GLM) were used to compare the incremental costs of CML patients with vs without progression. RESULTS: Of the overall study population, 587 (7%) experienced disease progression and 7,504 (93%) did not. On the index date, of patients with progression, ∼ 31% were treated with allogeneic hematopoietic cell transplant and 69% with chemotherapy. During the baseline period, mean total healthcare costs, including costs for hospitalizations and outpatient costs, were significantly greater for CML patients with progression as compared to those without progression ($143,778 vs $53,143, p < .001). During the follow-up, mean total healthcare costs, costs for hospitalizations, and outpatient medical service costs were substantially greater for patients with progression as compared to those without progression; however, costs for outpatient prescriptions were less for patients who progressed. When patient characteristics were controlled for, mean incremental 1-year cost for CML patients with vs without progression was $270,925 (confidence interval = $235,290-$311,958, p < .001). CONCLUSIONS: The healthcare burden, in terms of healthcare resource utilization and costs, of patients with CML progression is substantial. Healthcare providers and payers should consider various strategies to minimize the rate of CML progression.

Major bleeding risk and healthcare economic outcomes of non-valvular atrial fibrillation patients newly-initiated with oral anticoagulant therapy in the real-world setting.

AIMS: This study compared the risk for major bleeding (MB) and healthcare economic outcomes of patients with non-valvular atrial fibrillation (NVAF) after initiating treatment with apixaban vs rivaroxaban, dabigatran, or warfarin. METHODS: NVAF patients who initiated apixaban, rivaroxaban, dabigatran, or warfarin were identified from the IMS Pharmetrics Plus database (January 1, 2013-September 30, 2015). Propensity score matching (PSM) was used to balance differences in patient characteristics between study cohorts: patients treated with apixaban vs rivaroxaban, apixaban vs dabigatran, and apixaban vs warfarin. Risk of hospitalization and healthcare costs (all-cause and MB-related) were compared between matched cohorts during the follow-up. RESULTS: During the follow-up, risks for all-cause (hazard ratio [HR] = 1.44, 95% confidence interval [CI] = 1.2-1.7) and MB-related (HR = 1.57, 95% CI = 1.0-2.4) hospitalizations were significantly greater for patients treated with rivaroxaban vs apixaban. Adjusted total all-cause healthcare costs were significantly lower for patients treated with apixaban vs rivaroxaban ($3,950 vs $4,333 per patient per month [PPPM], p = .002) and MB-related medical costs were not statistically significantly different ($100 vs $233 PPPM, p = .096). Risk for all-cause hospitalization (HR = 1.98, 95% CI = 1.6-2.4) was significantly greater for patients treated with dabigatran vs apixaban, although total all-cause healthcare costs were not statistically different. Risks for all-cause (HR = 2.22, 95% CI = 1.9-2.5) and MB-related (HR = 2.05, 95% CI = 1.4-3.0) hospitalizations were significantly greater for patients treated with warfarin vs apixaban. Total all-cause healthcare costs ($3,919 vs $4,177 PPPM, p = .025) and MB-related medical costs ($96 vs $212 PPPM, p = .026) were significantly lower for patients treated with apixaban vs warfarin. LIMITATIONS: This retrospective database analysis does not establish causation. CONCLUSIONS: In the real-world setting, compared with rivaroxaban and warfarin, apixaban is associated with reduced risk of hospitalization and lower healthcare costs. Compared with dabigatran, apixaban is associated with lower risk of hospitalizations.

Using Health Care Claims Data to Assess the Prevalence of Hodgkin Lymphoma and Relapsed or Refractory Hodgkin Lymphoma in the United States.

PURPOSE: Although most patients with Hodgkin lymphoma (HL) respond to primary therapy, some patients experience relapses or are refractory to treatment (RR-HL). The objectives of this study were to investigate the prevalence of HL and RR-HL in the United States by using a large health care claims database. METHODS: Patients with ≥1 diagnosis for HL between January 1, 2013, and September 30, 2014 (prevalence assessment period), in the MarketScan Commercial and Medicare databases were identified. RR-HL patients were identified as any HL patient with any record for either an autologous stem cell transplantation (ASCT) or brentuximab vedotin (BV) treatment between January 1, 2010, and September 30, 2014 (entire study period). Prevalence rates of HL and RR-HL were calculated as the number of patients with HL or RR-HL divided by the total number of persons with insurance enrollment during the prevalence assessment period (January 1, 2013-September 30, 2014) in the MarketScan databases. Age- and sex-specific prevalence rates for HL and RR-HL were estimated. The estimated prevalence rates based on the claims database analysis were applied to the US national population estimates from the US Census Bureau to project the national prevalence of HL and RR-HL in the United States. FINDINGS: Of persons with any insurance enrollment in the MarketScan databases during the prevalence assessment period (N = 58,968,235), 24,812 (0.04%) were identified as having HL (mean age, 48.6 years) between January 1, 2013, and September 30, 2014. Of this HL population, 712 (2.87%) were identified as RR-HL patients, with 432 (1.74%) having received ASCT, 199 (0.80%) having received BV, and 81 (0.33%) having received both ASCT and BV treatments during the study period. According to the national projection according to the US Census population estimate, the overall number of persons with HL in the United States was estimated at 149,615 (469.2 per 1 million) in 2014, with 2.72% (N = 4077; 12.8 per 1 million) having RR-HL. IMPLICATIONS: Among patients in the United States with HL, the proportion of RR-HL patients during the study period was estimated at <3% of the HL population.