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: updated analysis.

OBJECTIVE: To provide an updated comparison of the risk and cost of stroke/systemic embolism (SE) and major bleeding between direct oral anticoagulants (DOAC: apixaban, rivaroxaban, dabigatran) and warfarin among non-valvular atrial fibrillation (NVAF) patients. METHODS: Adults (≥65 years) initiating warfarin or DOACs between 1 January 2013 and 31 December 2014 were selected from the Medicare database and propensity scores matched 1:1 to balance baseline 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 in each matched cohort. RESULTS: Of the 264,479 eligible patients, 38,740 apixaban-warfarin pairs, 76,677 rivaroxaban-warfarin pairs, and 20,955 dabigatran-warfarin pairs were matched. Apixaban (Hazard Ratio [HR] = 0.46; 95% Confidence Interval [CI] 0.38-0.56) and rivaroxaban (HR = 0.71; 95% CI 0.63-0.80) were associated with a significantly lower risk of stroke/SE compared to warfarin. Apixaban (HR = 0.57; 95% CI 0.51-0.63) and dabigatran (HR = 0.80; 95% CI 0.70-0.90) were associated with a significantly lower risk of major bleeding; rivaroxaban (HR = 1.14; 95% CI 1.07-1.21) was associated with a significantly higher risk of major bleeding compared to warfarin. Compared to warfarin, apixaban and rivaroxaban had significantly lower stroke/SE-related medical costs; and apixaban and dabigatran had significantly lower major bleeding-related medical costs. CONCLUSIONS: This real-world analysis showed DOACs to be associated with a lower risk of stroke/SE and major bleeding, and lower medical costs compared to warfarin. Among them, only apixaban appears to be associated with a significantly lower risk of all three outcomes collectively: stroke/SE, major bleeding, and lower related medical costs compared to warfarin.

Real-world evidence on survival, adverse events, and health care burden in Medicare patients with mantle cell lymphoma.

Most data on overall survival (OS) and adverse events (AEs) in patients with mantle cell lymphoma (MCL) are from controlled trials; therefore, in this population-based study, we retrospectively assessed treatment patterns, OS, and AEs in MCL patients initiating systemic treatment during 2013-2015 using the United States Medicare claims database. Among 1390 eligible patients (median age = 74 years), chemoimmunotherapy with bendamustine/rituximab (BR) was the preferred choice in first-line (35.3%), followed by ibrutinib (33.5%), rituximab (9.1%), and rituximab/cyclophosphamide/doxorubicin/vincristine (R-CHOP) (6.8%). Twenty-four-month OS was 73% for BR; 47%, ibrutinib; 72%, rituximab; and 71%, R-CHOP. For the four most commonly used regimens, neutropenia, anemia, hypertension, and infection were the most frequent AEs. Patients with ≥3 AEs had nearly four times higher monthly costs than those with 0-2 AEs in the first observed therapy line. Findings demonstrate a substantial increase in the economic burden as the number of AEs increased among the Medicare MCL patients.

Overall survival, adverse events, and economic burden in patients with chronic lymphocytic leukemia receiving systemic therapy: Real-world evidence from the medicare population.

BACKGROUND: Information on overall survival (OS) and adverse events (AEs) in patients with chronic lymphocytic leukemia (CLL) is mostly available from clinical trials. We therefore conducted a population-based retrospective cohort study to assess OS, incidence of AEs, and economic burden in real-world practice among Medicare patients treated for CLL. METHODS: Patients with CLL receiving ≥1 systemic therapy from 2013 to 2015 were selected from the Medicare claims database and followed from the start of first observed systemic therapy (index date) through December 2016 or death. OS for patients receiving each of the most commonly observed treatments was estimated by the Kaplan-Meier method. AEs were assessed among patients receiving these treatments across all observed lines of therapy. All-cause direct medical costs were assessed from the Medicare system perspective. RESULTS: Among 7,965 eligible patients across all observed therapy lines, ibrutinib monotherapy (Ibr; n = 2,708), chlorambucil monotherapy (Clb; n = 1,620), and bendamustine/rituximab (BR; n = 1,485) were the most common treatments. For first observed therapy, 24-month OS estimates for Ibr, Clb, and BR recipients were 69% (95% CI = 68%-71%), 68% (95% CI = 65%-71%), and 79% (95% CI = 77%-81%) respectively. The most frequently recorded AEs in patients receiving these treatments in any observed line of therapy were neutropenia, hypertension, anemia, and infection. For all patients, the mean monthly all-cause cost during the follow-up period was $8,974 (SD = $11,562); cost increased by the number of AEs, from $5,144 (SD = $5,409) among those with 1-2 AEs to $10,077 (SD = $12,542) among those with ≥6 AEs. CONCLUSION: Over two-thirds of patients survived at least 2 years after starting their first observed therapy for CLL. Our findings highlight considerable susceptibility to AEs and unmet medical need in Medicare patients with CLL treated in routine practice. Medicare incurred substantial economic burden following initiation of systemic therapy, and patients with greater numbers of AEs accounted disproportionately for the high overall cost of CLL management.

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.

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.

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.