A Real-World Observational Study of Hospitalization and Health Care Costs Among Nonvalvular Atrial Fibrillation Patients Prescribed Oral Anticoagulants in the U.S. Medicare Population.

This article has been corrected. Please see J Manag Care Spec Pharm, 2020;26(5):682 BACKGROUND: Clinical trials have shown that direct oral anticoagulants (DOACs)-including dabigatran, rivaroxaban, apixaban, and edoxaban-are at least as effective and safe as warfarin for the risk of stroke/systemic embolism (SE) and major bleeding (MB) in patients with atrial fibrillation (AF). However, few studies have compared oral anticoagulants (OACs) among elderly patients. OBJECTIVE: To compare hospitalization risks (all-cause, stroke/SE-related, and MB-related) and associated health care costs among elderly nonvalvular AF (NVAF) patients in the Medicare population who initiated warfarin, dabigatran, rivaroxaban, or apixaban. METHODS: Patients (aged ≥ 65 years) initiating warfarin or DOACs (apixaban, rivaroxaban, and dabigatran) were selected from the Centers for Medicare & Medicaid Services database from January 1, 2013, to December 31, 2014. Patients initiating each OAC were matched 1:1 to apixaban patients using propensity score matching to balance demographic and clinical characteristics. Cox proportional hazards models were used to estimate the risk of hospitalization of each OAC versus apixaban. Generalized linear models and two-part models with bootstrapping were used to compare all-cause health care costs and stroke/SE- and MB-related medical costs between matched cohorts. RESULTS: Of the 264,479 eligible patients, 77,480 warfarin-apixaban, 41,580 dabigatran-apixaban, and 77,640 rivaroxaban-apixaban patients were matched. The OACs were associated with a significantly higher risk of all-cause hospitalization compared with apixaban (warfarin: HR = 1.27, 95% CI = 1.23-1.31, P < 0.001; dabigatran: HR = 1.13, 95% CI = 1.08-1.18, P < 0.001; and rivaroxaban: HR = 1.22, 95% CI = 1.18-1.26, P < 0.001) and were associated with a significantly higher risk of hospitalization due to stroke/SE (warfarin: HR = 2.18, 95% CI = 1.80-2.64, P < 0.001; dabigatran: HR = 1.45, 95% CI = 1.12-1.88, P = 0.006; and rivaroxaban: HR = 1.40, 95% CI = 1.14-1.71, P = 0.001). Also, the OACs were associated with significantly higher risk of hospitalization due to MB-related conditions compared with apixaban (warfarin: HR = 1.76, 95% CI = 1.59-1.95, P < 0.001; dabigatran: HR = 1.44, 95% CI = 1.23-1.68, P < 0.001; and rivaroxaban: HR = 1.89, 95% CI = 1.71-2.09, P < 0.001). Compared with apixaban, warfarin ($3,577 vs. $3,183, P < 0.001); dabigatran ($3,217 vs. $3,060, P < 0.001); and rivaroxaban ($3,878 vs. $3,180, P < 0.001) had significantly higher all-cause total health care costs per patient per month. Patients initiating the OACs had significantly higher MB-related medical costs compared with apixaban: warfarin ($472 vs. $269; P < 0.001); dabigatran ($364 vs. $245, P < 0.001); and rivaroxaban ($493 vs. $270, P < 0.001). Warfarin was also associated with higher stroke/SE-related medical costs compared with apixaban ($124 vs. $62, P < 0.001). CONCLUSIONS: This real-world study showed that among elderly NVAF patients in the Medicare population, apixaban was associated with significantly lower risks of all-cause, stroke/SE-related, and MB-related hospitalizations compared with warfarin, dabigatran, and rivaroxaban. Accordingly, apixaban showed significantly lower all-cause health care costs and MB-related medical costs. DISCLOSURES: This study was funded by Bristol Myers Squibb and Pfizer. Amin is an employee of the University of California, Irvine, and was a paid consultant to Bristol Myers Squibb in connection with this study and the development of this manuscript. He has served as a consultant and/or speaker for Bristol Myers Squibb, Pfizer, and Boehringer Ingelheim. Keshishian and Zhang are employees of STATinMED Research, a paid consultant to Pfizer and Bristol Myers Squibb in connection with this study and the development of this manuscript. Trocio, Dina, Mardekian, and Liu are employees of Pfizer, with ownership of stocks in Pfizer. Le, Rosenblatt, Nadkarni, and Vo are employees of Bristol Myers Squibb. Rosenblatt and Vo have ownership of stocks in Bristol Myers Squibb. Baser has no conflicts to disclose.

Real-World Comparative Effectiveness, Safety, and Health Care Costs of Oral Anticoagulants in Nonvalvular Atrial Fibrillation Patients in the U.S. Department of Defense Population.

BACKGROUND: The ARISTOTLE trial demonstrated that apixaban had significantly lower rates of stroke/systemic embolism (SE) and major bleeding than warfarin; however, no direct clinical trials between apixaban and other direct oral anticoagulants (DOACs) are available. Few real-world studies comparing the effectiveness and safety between DOACs have been conducted. OBJECTIVE: To compare effectiveness, safety, and health care costs among oral anticoagulants (OACs) for nonvalvular atrial fibrillation (NVAF) patients in the U.S. Department of Defense (DoD) population. METHODS: Adult NVAF patients initiating warfarin or DOACs (apixaban, rivaroxaban, and dabigatran) were selected from U.S. DoD data from January 1, 2013, to September 30, 2015. The first OAC claim date was designated as the index date. Patients initiating another OAC were matched 1:1 to apixaban patients using propensity score matching to balance demographics and clinical characteristics. Cox proportional hazards models were used to estimate the risk of stroke/SE and major bleeding for each OAC versus apixaban. Generalized linear and two-part models with bootstrapping were used to compare all-cause health care costs and stroke/SE-related and major bleeding-related medical costs. RESULTS: Of the 41,001 eligible patients, 7,607 warfarin-apixaban, 4,129 dabigatran-apixaban, and 11,284 rivaroxaban-apixaban pairs were matched. Warfarin (HR = 1.84; 95% CI = 1.30-2.59; P < 0.001) and rivar-oxaban (HR = 1.46; 95% CI = 1.08-1.98; P = 0.015) were associated with a significantly higher risk of stroke/SE compared with apixaban. Dabigatran (HR = 1.17; 95% CI = 0.68-2.03; P = 0.573) was associated with a numerically higher risk of stroke/SE compared with apixaban. Warfarin (HR = 1.53; 95% CI = 1.24-1.89; P < 0.001), dabigatran (HR = 1.76; 95% CI = 1.27-2.43; P < 0.001), and rivaroxaban (HR = 1.59; 95% CI = 1.34-1.89; P < 0.001) were associated with higher risks of major bleeding compared with apixaban. Compared with apixaban, patients prescribed warfarin incurred numerically higher all-cause total health care costs per patient per month (PPPM) ($2,498 vs. $2,277; P = 0.148) and significantly higher stroke/SE-related ($118 vs. $46; P = 0.012) and major bleeding-related ($166 vs. $76; P = 0.003) medical costs. Dabigatran patients incurred numerically higher all-cause total health care PPPM costs ($2,372 vs. $2,143; P = 0.150) and stroke/SE-related medical costs ($61 vs. $32; P = 0.240) but significantly higher major bleeding-related costs ($114 vs. $58; P = 0.025). Rivaroxaban patients incurred significantly higher all-cause total health care costs ($2,546 vs. $2,200; P < 0.001) and major bleeding-related medical costs PPPM ($137 vs. $69; P < 0.001) but numerically higher stroke/SE-related medical costs PPPM ($58 vs. $38; P = 0.057). CONCLUSIONS: Among NVAF patients in the U.S. DoD population, warfarin and rivaroxaban were associated with a significantly higher risk of stroke/SE and major bleeding compared with apixaban. Dabigatran use was associated with a numerically higher risk of stroke/SE and a significantly higher risk of major bleeding compared with apixaban. Warfarin and dabigatran incurred numerically higher all-cause total health care costs compared with apixaban. Rivaroxaban was associated with significantly higher all-cause total health care costs compared with apixaban. DISCLOSURES This study was funded by Bristol-Myers Squibb and Pfizer, which were involved in the study design, as well as in the writing and revision of the manuscript. Keshishian and Zhang are paid employees of STATinMED Research, which was paid by Bristol-Myers Squibb and Pfizer to conduct this study and develop the manuscript. Gupta, Rosenblatt, Hede, and Nadkarni are paid employees of Bristol-Myers Squibb. Trocio, Dina, Mardekian, Liu, and Shank are paid employees of Pfizer.

A Real-World Observational Study of Hospitalization and Health Care Costs Among Nonvalvular Atrial Fibrillation Patients Prescribed Oral Anticoagulants in the U.S. Medicare Population.

BACKGROUND: Clinical trials have shown that direct oral anticoagulants (DOACs)-including dabigatran, rivaroxaban, apixaban, and edoxaban-are at least as effective and safe as warfarin for the risk of stroke/systemic embolism (SE) and major bleeding (MB) in patients with atrial fibrillation (AF). However, few studies have compared oral anticoagulants (OACs) among elderly patients. OBJECTIVE: To compare hospitalization risks (all-cause, stroke/SE-related, and MB-related) and associated health care costs among elderly nonvalvular AF (NVAF) patients in the Medicare population who initiated warfarin, dabigatran, rivaroxaban, or apixaban. METHODS: Patients (aged ≥ 65 years) initiating warfarin or DOACs (apixaban, rivaroxaban, and dabigatran) were selected from the Centers for Medicare & Medicaid Services database from January 1, 2013, to December 31, 2014. Patients initiating each OAC were matched 1:1 to apixaban patients using propensity score matching to balance demographic and clinical characteristics. Cox proportional hazards models were used to estimate the risk of hospitalization of each OAC versus apixaban. Generalized linear models and two-part models with bootstrapping were used to compare all-cause health care costs and stroke/SE- and MB-related medical costs between matched cohorts. RESULTS: Of the 186,132 eligible patients, 41,606 warfarin-apixaban, 30,836 dabigatran-apixaban, and 41,608 rivaroxaban-apixaban pairs were matched. The OACs were associated with a significantly higher risk of all-cause hospitalization compared with apixaban (warfarin: HR = 1.33, 95% CI = 1.27-1.38, P < 0.001; dabigatran: HR = 1.17, 95% CI = 1.11-1.23, P < 0.001; and rivaroxaban: HR = 1.27, 95% CI = 1.22-1.32, P < 0.001) and were associated with a significantly higher risk of hospitalization due to stroke/SE (warfarin: HR = 2.51, 95% CI = 1.92-3.29, P < 0.001; dabigatran: HR = 2.24, 95% CI = 1.60-3.13, P < 0.001; and rivaroxaban: HR = 1.74, 95% CI = 1.31-2.30, P < 0.001). Also, the OACs were associated with significantly higher risk of hospitalization due to MB-related conditions compared with apixaban (warfarin: HR = 1.96, 95% CI = 1.71-2.23, P < 0.001; dabigatran: HR = 1.48; 95% CI = 1.25-1.76, P < 0.001; and rivaroxaban: HR = 2.17, 95% CI = 1.91-2.48, P < 0.001). Compared with apixaban, warfarin ($3,747 vs. $3,061, P < 0.001); dabigatran ($3,230 vs. $2,951, P < 0.001); and rivaroxaban ($3,950 vs. $3,060, P < 0.001) had significantly higher all-cause total health care costs per patient per month. Patients initiating the OACs also had significantly higher stroke/SE- and MB-related medical costs compared with apixaban: warfarin (stroke/SE = $135 vs. $60, P = 0.001; MB = $537 vs. $286, P < 0.001); dabigatran (stroke/SE = $94 vs. $62, P = 0.045; MB = $373 vs. $277, P = 0.010); and rivaroxaban (stroke/SE = $91 vs. $60, P = 0.008; MB = $524 vs. $287, P < 0.001). CONCLUSIONS: This real-world study showed that among elderly NVAF patients in the Medicare population, apixaban was associated with significantly lower risks of all-cause, stroke/SE-related, and MB-related hospitalizations compared with warfarin, dabigatran, and rivaroxaban. Accordingly, apixaban showed significantly lower all-cause health care costs and stroke/SE- and MB-related medical costs. DISCLOSURES: This study was funded by Bristol-Myers Squibb and Pfizer. Amin is an employee of the University of California, Irvine, and was a paid consultant to Bristol-Myers Squibb in connection with this study and the development of this manuscript. Keshishian and Zhang are employees of STATinMED Research, a paid consultant to Pfizer and Bristol-Myers Squibb in connection with this study and the development of this manuscript. Trocio, Dina, Mardekian, and Liu are employees of Pfizer, with ownership of stocks in Pfizer. Le, Rosenblatt, Nadkarni, and Vo are employees of Bristol-Myers Squibb. Rosenblatt and Vo have ownership of stocks in Bristol-Myers Squibb. Baser has no conflicts to disclose.

Estimated prevalence of undiagnosed atrial fibrillation in the United States.

INTRODUCTION: As atrial fibrillation (AF) is often asymptomatic, it may remain undiagnosed until or even after development of complications, such as stroke. Consequently the observed prevalence of AF may underestimate total disease burden. METHODS: To estimate the prevalence of undiagnosed AF in the United States, we performed a retrospective cohort modeling study in working age (18-64) and elderly (≥65) people using commercial and Medicare administrative claims databases. We identified patients in years 2004-2010 with incident AF following an ischemic stroke. Using a back-calculation methodology, we estimated the prevalence of undiagnosed AF as the ratio of the number of post-stroke AF patients and the CHADS2-specific stroke probability for each patient, adjusting for age and gender composition based on United States census data. RESULTS: The estimated prevalence of AF (diagnosed and undiagnosed) was 3,873,900 (95%CI: 3,675,200-4,702,600) elderly and 1,457,100 (95%CI: 1,218,500-1,695,800) working age adults, representing 10.0% and 0.92% of the respective populations. Of these, 698,900 were undiagnosed: 535,400 (95%CI: 331,900-804,400) elderly and 163,500 (95%CI: 17,700-400,000) working age adults, representing 1.3% and 0.09% of the respective populations. Among all undiagnosed cases, 77% had a CHADS2 score ≥1, and 56% had CHADS2 score ≥2. CONCLUSIONS: Using a back-calculation approach, we estimate that the total AF prevalence in 2009 was 5.3 million of which 0.7 million (13.1% of AF cases) were undiagnosed. Over half of the modeled population with undiagnosed AF was at moderate to high risk of stroke.

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.

Real-world comparison of all-cause hospitalizations, hospitalizations due to stroke and major bleeding, and costs for non-valvular atrial fibrillation patients prescribed oral anticoagulants in a US health plan.

AIMS: To compare the risk of all-cause hospitalization and hospitalizations due to stroke/systemic embolism (SE) and major bleeding, as well as associated healthcare costs for non-valvular atrial fibrillation (NVAF) patients initiating apixaban, dabigatran, rivaroxaban, or warfarin. MATERIALS AND METHODS: NVAF patients initiating apixaban, dabigatran, rivaroxaban, or warfarin were selected from the OptumInsight Research Database from January 1, 2013-September 30, 2015. Propensity score matching (PSM) was performed between apixaban and each oral anticoagulant. Cox models were used to estimate the risk of stroke/SE and major bleeding. Generalized linear and 2-part models were used to compare healthcare costs. RESULTS: Of the 47,634 eligible patients, 8,328 warfarin-apixaban pairs, 3,557 dabigatran-apixaban pairs, and 8,440 rivaroxaban-apixaban pairs were matched. Compared to apixaban, warfarin patients were associated with a significantly higher risk of all-cause (hazard ratio [HR] = 1.30; 95% confidence interval [CI] = 1.21-1.40) as well as stroke/SE-related (HR = 1.60; 95% CI = 1.23-2.07) and major bleeding-related (HR = 1.95; 95% CI = 1.60-2.39) hospitalization; rivaroxaban patients were associated with a higher risk of all-cause (HR = 1.15; 95% CI = 1.07-1.24) and major bleeding-related hospitalization (HR = 1.71; 95% CI = 1.39-2.10); and dabigatran patients were associated with a higher risk of major bleeding hospitalization (HR = 1.46, 95% CI = 1.02-2.10). Warfarin patients had significantly higher major bleeding-related and total all-cause healthcare costs compared to apixaban patients. Rivaroxaban patients had significantly higher major bleeding-related costs compared to apixaban patients. No significant results were found for the remaining comparisons. LIMITATIONS: No causal relationships can be concluded, and unobserved confounders may exist in this retrospective database analysis. CONCLUSIONS: This study demonstrated a significantly higher risk of hospitalization (all-cause, stroke/SE, and major bleeding) associated with warfarin, a significantly higher risk of major bleeding hospitalization associated with dabigatran or rivaroxaban, and a significantly higher risk of all-cause hospitalization associated with rivaroxaban compared to apixaban. Lower major bleeding-related costs were observed for apixaban patients compared to warfarin and rivaroxaban patients.

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.

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.

Risk of stroke/systemic embolism, major bleeding and associated costs in non-valvular atrial fibrillation patients who initiated apixaban, dabigatran or rivaroxaban compared with warfarin in the United States Medicare population.

OBJECTIVE: To compare the risk and cost of stroke/systemic embolism (SE) and major bleeding between each direct oral anticoagulant (DOAC) and warfarin among non-valvular atrial fibrillation (NVAF) patients. METHODS: Patients (≥65 years) initiating warfarin or DOACs (apixaban, rivaroxaban, and dabigatran) were selected from the Medicare database from 1 January 2013 to 31 December 2014. Patients initiating each DOAC were matched 1:1 to warfarin patients using propensity score matching to balance demographics and clinical characteristics. Cox proportional hazards models were used to estimate the risks of stroke/SE and major bleeding of each DOAC vs. warfarin. Two-part models were used to compare the stroke/SE- and major-bleeding-related medical costs between matched cohorts. RESULTS: Of the 186,132 eligible patients, 20,803 apixaban-warfarin pairs, 52,476 rivaroxaban-warfarin pairs, and 16,731 dabigatran-warfarin pairs were matched. Apixaban (hazard ratio [HR] = 0.40; 95% confidence interval [CI] 0.31, 0.53) and rivaroxaban (HR = 0.72; 95% CI 0.63, 0.83) were significantly associated with lower risk of stroke/SE compared to warfarin. Apixaban (HR = 0.51; 95% CI 0.44, 0.58) and dabigatran (HR = 0.79; 95% CI 0.69, 0.91) were significantly associated with lower risk of major bleeding; rivaroxaban (HR = 1.17; 95% CI 1.10, 1.26) was significantly associated with higher risk of major bleeding compared to warfarin. Compared to warfarin, apixaban ($63 vs. $131) and rivaroxaban ($93 vs. $139) had significantly lower stroke/SE-related medical costs; apixaban ($292 vs. $529) and dabigatran ($369 vs. $450) had significantly lower major bleeding-related medical costs. CONCLUSIONS: Among the DOACs in the study, only apixaban is associated with a significantly lower risk of stroke/SE and major bleeding and lower related medical costs compared to warfarin.

Physician and Patient Preferences for Nonvalvular Atrial Fibrillation Therapies.

OBJECTIVES: The objective of this study was to compare patient and physician preferences for different antithrombotic therapies used to treat nonvalvular atrial fibrillation (NVAF). METHODS: Patients diagnosed with NVAF and physicians treating such patients completed 12 discrete choice questions comparing NVAF therapies that varied across five attributes: stroke risk, major bleeding risk, convenience (no regular blood testing/dietary restrictions), dosing frequency, and patients' out-of-pocket cost. We used a logistic regression to estimate the willingness-to-pay (WTP) value for each attribute. RESULTS: The 200 physicians surveyed were willing to trade off $38 (95% confidence interval [CI] $22 to $54] in monthly out-of-pocket cost for a 1% (absolute) decrease in stroke risk, $14 (95% CI $8 to $21) for a 1% decrease in major bleeding risk, and $34 (95% CI $9 to $60) for more convenience. The WTP value among 201 patients surveyed was $30 (95% CI $18 to $42) for reduced stroke risk, $16 (95% CI $9 to $24) for reduced bleeding risk, and -$52 (95% CI -$96 to -6) for convenience. The WTP value for convenience among patients using warfarin was $9 (95% CI $1 to $18) for more convenience, whereas patients not currently on warfarin had a WTP value of -$90 (95% CI -$290 to -$79). Both physicians' and patients' WTP value for once-daily dosing was not significantly different from zero. On the basis of survey results, 85.0% of the physicians preferred novel oral anticoagulants (NOACs) to warfarin. NOACs (73.0%) were preferred among patients using warfarin, but warfarin (78.2%) was preferred among patients not currently using warfarin. Among NOACs, both patients and physicians preferred apixaban. CONCLUSIONS: Both physicians and patients currently using warfarin preferred NOACs to warfarin. Patients not currently using warfarin preferred warfarin over NOACs because of an apparent preference for regular blood testing/dietary restrictions.

Comparison of hospital length of stay and hospitalization costs among patients with non-valvular atrial fibrillation treated with apixaban or warfarin: An early view.

OBJECTIVE: To quantify and compare hospital length of stay (LOS) and costs between hospitalized non-valvular atrial fibrillation (NVAF) patients treated with either apixaban or warfarin via a large claims database. METHODS: Adult patients hospitalized with AF were selected from the Premier Perspective Claims Database (01JAN2013-31MARCH2014). Patients with evidence of valvular heart disease, valve replacement procedures, or pregnancy during the index hospitalization were excluded. Patients treated with apixaban or warfarin during hospitalization were identified. Propensity score matching (PSM) was performed to control for baseline imbalances between patients treated with apixaban or warfarin. Primary outcomes were hospital LOS (days), post-medication administration LOS, and index hospitalization costs, and were compared using paired t-tests in the matched sample. RESULTS: Before PSM, 2894 apixaban and 124,174 warfarin patients were identified. Patients treated with warfarin were older and sicker compared to those treated with apixaban. After applying PSM, a total of 2886 patients were included in each cohort, and baseline characteristics were balanced. The mean (standard deviation [SD] and median) hospital LOS was significantly (p = 0.002) shorter for patients treated with apixaban for 5.1 days (5.7 and 3) compared to warfarin for 5.5 days (4.8 and 4). The trend appeared consistent in the hospital LOS from point of apixaban or warfarin administration to discharge (4.5 vs 4.7 days, p = 0.051). Patients administered apixaban incurred significantly lower hospitalization costs compared to those administered warfarin ($11,262 vs $12,883; p < 0.001). CONCLUSIONS: Among NVAF patients, apixaban treatment was associated with significantly shorter hospital LOS and lower costs when compared to warfarin treatment.

Warfarin time in therapeutic range and its impact on healthcare resource utilization and costs among patients with nonvalvular atrial fibrillation.

BACKGROUND: Warfarin is efficacious for reducing stroke risk among patients with nonvalvular atrial fibrillation (NVAF). However, the efficacy and safety of warfarin are influenced by its time in therapeutic range (TTR). OBJECTIVE: To assess differences in healthcare resource utilization and costs among NVAF patients with low (<60%) and high (≥60%) warfarin TTRs in an integrated delivery network (IDN) setting. METHODS: Patients with NVAF were identified from an electronic medical record database. Patients were required to have ≥6 international normalized prothrombin time ratio (INR) tests. NVAF patients were grouped into two cohorts: those with warfarin TTR <60% (low TTR) and those with warfarin TTR ≥60% (high TTR). Healthcare resource utilization and costs were evaluated during a 12 month follow-up period. Multivariable regressions were used to assess the impact of different warfarin TTRs on healthcare costs. RESULTS: Among the study population, greater than half (54%, n = 1595) had a low TTR, and 46% (n = 1356) had a high TTR. Total all-cause healthcare resource utilization was higher among patients in the low TTR cohort vs. the high TTR cohort (number of encounters: 70.2 vs. 56.1, p < 0.001). After adjusting for patient characteristics, total all-cause healthcare costs and stroke-related healthcare costs were $2398 (p < 0.001) and $687 (p = 0.02) higher, respectively, for patients in the low TTR cohort vs. the high TTR cohort. LIMITATIONS: In this retrospective study, we were only able to evaluate the association and not the causality between healthcare resource utilization and costs with the different warfarin TTRs. CONCLUSION: Many warfarin-treated NVAF patients have a low warfarin TTR. NVAF patients with low vs. patients with high warfarin TTR used healthcare resources to a greater extent, which was reflected in higher healthcare costs.

Real-World Medical Cost Avoidance When New Oral Anticoagulants are Used Versus Warfarin for Venous Thromboembolism in the United States.

OBJECTIVE: Real-world medical cost avoidances from a US payer perspective were estimated when new oral anticoagulants (NOACs) are used instead of warfarin for the treatment of patients with venous thromboembolism (VTE). METHODS: Reductions in real-world event rates of recurrent VTE and MB were obtained by applying rate reductions from the NOACs versus warfarin trials to the Worcester population. Incremental annual medical costs among patients with VTE and MB from a US payer perspective were obtained from the literature or claims databases. Differences in total medical costs for patients treated with NOACs versus warfarin were then estimated. Univariate and Monte Carlo sensitivity analyses were additionally carried out. RESULTS: The annual total medical cost avoidances versus warfarin were greatest for VTE patients treated with apixaban (-US$4440 per patient-year [ppy]), followed by those treated with rivaroxaban (-US$2971 ppy), edoxaban (-US$1957 ppy), and dabigatran (-US$572 ppy). The medical cost avoidances remained consistent under sensitivity analyses. CONCLUSION: Based on real-world data, when any of the evaluated NOACs are used instead of warfarin for treatment of patients with acute VTE, annual medical costs are reduced. Of the NOACs, apixaban has the greatest real-world medical cost avoidance, as its use is associated with substantial reductions in both VTE and MB event rates.

Leveraging Real-World Evidence in Disease-Management Decision-Making with a Total Cost of Care Estimator.

BACKGROUND: Health management is becoming increasingly complex, given a range of care options and the need to balance costs and quality. The ability to measure and understand drivers of costs is critical for healthcare organizations to effectively manage their patient populations. Healthcare decision makers can leverage real-world evidence to explore the value of disease-management interventions in shifting total cost trends. OBJECTIVE: To develop a real-world, evidence-based estimator that examines the impact of disease-management interventions on the total cost of care (TCoC) for a patient population with nonvalvular atrial fibrillation (NVAF). METHODS: Data were collected from a patient-level real-world evidence data set that uses the IMS PharMetrics Health Plan Claims Database. Pharmacy and medical claims for patients meeting the inclusion or exclusion criteria were combined in longitudinal cohorts with a 180-day preindex and 360-day follow-up period. Descriptive statistics, such as mean and median patient costs and event rates, were derived from a real-world evidence analysis and were used to populate the base-case estimates within the TCoC estimator, an exploratory economic model that was designed to estimate the potential impact of several disease-management activities on the TCoC for a patient population with NVAF. Using Microsoft Excel, the estimator is designed to compare current direct costs of medical care to projected costs by varying assumptions on the impact of disease-management activities and applying the associated changes in cost trends to the affected populations. Disease-management levers are derived from literature-based concepts affecting costs along the NVAF disease continuum. The use of the estimator supports analyses across 4 US geographic regions, age, cost types, and care settings during 1 year. RESULTS: All patients included in the study were continuously enrolled in their health plan (within the IMS PharMetrics Health Plan Claims Database) between July 1, 2010, and June 30, 2012. Patients were included in the final analytic file and were indexed based on (1) the service date of the first claim within the selection window (December 28, 2010-July 11, 2011) with a diagnosis of NVAF, or (2) the service date of the second claim for an NVAF medication of interest during the same selection window. The model estimates the current trends in national benchmark data for a hypothetical health plan with 1 million covered lives. The annual total direct healthcare costs (allowable and patient out-of-pocket costs) of managing patients with NVAF in this hypothetical plan are estimated at $184,981,245 ($25,754 per patient, for 7183 patients). A potential 25% improvement from the base-case disease burden and disease management could translate into TCoC savings from reducing the excess costs related to hypertension (-5.3%) and supporting the use of an appropriate antithrombotic treatment that prevents ischemic stroke (-0.7%) and reduces bleeding events (-0.1%). CONCLUSIONS: The use of the TCoC estimator supports population health management by providing real-world evidence benchmark data on NVAF disease burden and by quantifying the potential value of disease-management activities in shifting cost trends.

Incremental Health Care Burden of Bleeding Among Patients with Venous Thromboembolism in the United States.

BACKGROUND: The health care and economic burden of venous thromboembolism (VTE) has been evaluated in regard to acute VTE, VTE recurrence, and some VTE complications, such as postthrombotic syndrome, but the cost burden attributed to bleedings is not well understood. OBJECTIVE: To evaluate health care resource utilization and costs associated with major bleeding (MB) and clinically relevant nonmajor bleeding (CRNMB) among a large U.S. commercially and Medicare-insured population with VTE. METHODS: Patients (≥ 18 years of age, continuously insured) with a diagnosis of VTE between January 1, 2008, and December 31, 2011, were identified from the Truven Health Analytics Commercial and Medicare MarketScan databases. Patients who did not have any bleedings during the study period were grouped into a no-bleedings cohort and a random date after VTE diagnosis was selected as the index date. VTE patients who experienced MB within 1 year of the initial VTE diagnosis were grouped into a MB cohort, and patients without MB but with CRNMB were grouped into a CRNMB cohort. Baseline patient demographics and clinical characteristics were determined for study cohorts. All-cause and bleeding-related health care resource utilization and costs (inflation adjusted to 2013 level) during a 12-month follow-up period after the index date of the initial bleeding event were measured and compared. Descriptive statistics were used to evaluate differences in demographics, clinical characteristics, and unadjusted health care resource utilization and costs of patient cohorts. Multivariable generalized linear models were used to evaluate incremental health care costs of bleedings after adjusting for key patient characteristics.   RESULTS: Among the 112,885 patients identified with a VTE diagnosis, 14% (n = 15,897) had MB and 14% (n = 15,842) had CRNMB; 72% (n = 81,146) had neither of these events occur during the study period. The mean ages of the MB and CRNMB cohorts were both 63.6 years, while the mean age of the no-bleedings cohort was significantly lower at 59.6 years (P less than 0.001). Mean Charlson Comorbidity Index scores were highest for the MB cohort (3.2), followed by those of the CRNMB cohort (2.5) and the no-bleedings cohort (1.6). The MB cohort had the greatest proportion of patients with an initial VTE event of pulmonary embolism only (23.5%), followed by that of the CRNMB cohort (20.2%), and the no-bleedings cohort (16.7%). For MB and CRNMB cohorts, the total mean bleeding-related inpatient and outpatient costs during the follow-up period were $49,779 (SE = $820) and $2,187 ($89), respectively. After adjustment for key patient characteristics, the estimated mean differences in total bleeding-related medical costs were $45,367 ($1,853) for patients with MB and $2,140 ($88) for patients with CRNMB versus patients with no bleedings. CONCLUSIONS: Among patients with VTE diagnosis in the United States, approximately 28% have a bleeding event within 1 year of VTE diagnosis, and about half of these patients experience MB. Patients with MB have greatly elevated health care costs.

Economic Burden of Undiagnosed Nonvalvular Atrial Fibrillation in the United States.

Atrial fibrillation (AF) may be clinically silent and therefore undiagnosed. To date, no estimates of the direct medical cost of undiagnosed AF exist. We estimated the United States (US) incremental cost burden of undiagnosed nonvalvular AF nationally using administrative claims data. To calculate the incremental costs of undiagnosed AF, we compared annual medical costs (in 2014 US Dollars) for patients with AF compared to propensity-matched controls and multiplied this by estimates of undiagnosed AF prevalence derived from the same data sources. The study population included US residents aged ≥18 years with 24 months of continuous enrollment drawn from 2 large administrative claims databases. Mean per capita medical spending for patients with AF aged from 18 to 64 year was $38,861 (95% confidence interval [CI] $35,781 to $41,950) compared to $28,506 (95% CI $28,409 to $28,603) for similar patients without AF (incremental cost difference $10,355, p <0.001); total spending for patients aged ≥65 years with AF was $25,322 (95% CI $25,049 to $25,595) compared to $21,706 (95% CI $21,563 to $21,849) for similar patients without AF (incremental cost difference $3,616, p <0.001). Using estimates of the US prevalence of undiagnosed AF (596,000) drawn from the same data, we estimated that the US incremental cost burden of undiagnosed nonvalvular AF is $3.1 billion (95% CI $2.7 to $3.7 billion). In conclusion, the direct medical costs for patients with undiagnosed AF are greater than patients with similar observable characteristics without AF and strategies to identify and treat patients with undiagnosed AF could lead to sizable reductions in stroke sequelae and associated costs.

Comparison of differences in medical costs when new oral anticoagulants are used for the treatment of patients with non-valvular atrial fibrillation and venous thromboembolism vs warfarin or placebo in the US.

OBJECTIVE: Medical costs that may be avoided when any of the four new oral anticoagulants (NOACs), dabigatran, rivaroxaban, apixaban, and edoxaban, are used instead of warfarin for the treatment of non-valvular atrial fibrillation (NVAF) were estimated and compared. Additionally, the overall differences in medical costs were estimated for NVAF and venous thromboembolism (VTE) patient populations combined. METHODS: Medical cost differences associated with NOAC use vs warfarin or placebo among NVAF and VTE patients were estimated based on clinical event rates obtained from the published trial data. The clinical event rates were calculated as the percentage of patients with each of the clinical events during the trial periods. Univariate and multivariate sensitivity analyses were conducted for the medical-cost differences determined for NVAF patients. A hypothetical health plan population of 1 million members was used to estimate and compare the combined medical-cost differences of the NVAF and VTE populations and were projected in the years 2015-2018. RESULTS: In a year, the medical-cost differences associated with NOAC use instead of warfarin were estimated at -$204, -$140, -$495, and -$340 per patient for dabigatran, rivaroxaban, apixaban, and edoxaban, respectively. In 2014, among the hypothetical population, the medical-cost differences were -$3.7, -$4.2, -$11.5, and -$6.6 million for NVAF and acute VTE patients treated with dabigatran, rivaroxaban, apixaban, and edoxaban, respectively. In 2014, for the combined NVAF, acute VTE, and extended VTE patient populations, medical-cost differences were -$10.0, -$10.9, -$21.0, and -$21.0 million for dabigatran, rivaroxaban, 2.5 mg apixaban, and 5 mg apixaban, respectively. Medical-cost differences associated with use of NOACs were projected to steadily increase from 2014 to 2018. CONCLUSIONS: Medical costs are reduced when NOACs are used instead of warfarin/placebo for the treatment of NVAF or VTE, with apixaban being associated with the greatest reduction in medical costs.

Evaluation of medical costs avoided when new oral anticoagulants are used for extended treatment of venous thromboembolism based on clinical trial results.

This study evaluated avoidances in medical costs associated with clinical endpoints from randomized clinical trials that evaluated the efficacy and safety of the new oral anticoagulants (NOACs), dabigatran, rivaroxaban, and apixaban for extended treatment of patients with venous thromboembolism (VTE). Event rates of efficacy and safety endpoints from the clinical trials (RE-SONATE, EINSTEIN-EXT, and AMPLIFY-EXT) were obtained from published literature. Incremental annual medical costs among patients with clinical events from a US payer perspective were obtained from the literature or healthcare claims databases and inflation adjusted to 2013 costs. Differences in total medical costs associated with clinical endpoints for patients treated with NOACs versus placebo were then estimated. One-way univariate and Monte Carlo sensitivity analyses were additionally carried out. In all three NOAC trials lower rates of recurrent VTE occurred with NOAC use versus placebo. As a result of the reduction in VTE recurrence the overall medical costs avoided were -$2,794, -$2,948, -$4,249, and -$4,244 for VTE patients treated with dabigatran, rivaroxaban, apixaban 2.5 mg, and apixaban 5 mg respectively versus patients treated with placebo. Apixaban was associated with the greatest avoidance in medical costs, which was driven mainly by a greater reduced rate in recurrent VTE than other NOACs versus placebo and also a reduction in major bleeding rate. Further evaluation is needed to validate these results in the real-world setting.

Evaluation of medical costs associated with use of new oral anticoagulants compared with standard therapy among venous thromboembolism patients.

OBJECTIVE: This study evaluated differences in medical costs associated with clinical end-points from randomized clinical trials that compared the new oral anticoagulants (NOACs), dabigatran, rivaroxaban, apixaban, and edoxaban, to standard therapy for treatment of patients with venous thromboembolism (VTE). RESEARCH DESIGN AND METHODS: Event rates of efficacy and safety end-points from the clinical trials (RE-COVER, RE-COVER II, EINSTEIN-Pooled, AMPLIFY, Hokusai-VTE trial) were obtained from published literature. Incremental annual medical costs among patients with clinical events from a US payer perspective were obtained from the literature or healthcare claims databases and inflation adjusted to 2013 costs. Differences in total medical costs associated with clinical end-points for the NOACs vs standard therapy were then estimated. One-way and Monte Carlo sensitivity analyses were carried out. RESULTS: A lower rate of major bleedings was associated with use of any of the NOACs vs standard therapy. Except for dabigatran, use of NOACs was also associated with a lower rate of recurrent VTE/death. As a result of the reduction in clinical event rates, the overall medical cost differences were -$146, -$482, -$918, and -$344 for VTE patients treated with dabigatran, rivaroxaban, apixaban, and edoxaban, respectively, vs patients treated with standard therapy. CONCLUSIONS: When any of the four NOACs are used instead of standard therapy for acute VTE, treatment medical costs are reduced. Apixaban is associated with the greatest reduction in medical costs, which is driven by medical cost reductions associated with both efficacy and safety end-points. Further evaluation may be needed to validate these results in the real-world setting.