Risk of Stroke Outcomes in Atrial Fibrillation Patients Treated with Rivaroxaban and Warfarin.

OBJECTIVES: In a previous real-world study, rivaroxaban reduced the risk of stroke overall and severe stroke compared with warfarin in patients with nonvalvular atrial fibrillation (NVAF). The aim of this study was to assess the reproducibility in a different database of our previously observed results (Alberts M, et al. Stroke. 2020;51:549-555) on the risk of severe stroke among NVAF patients in a different population treated with rivaroxaban or warfarin. MATERIAL AND METHODS: This retrospective cohort study included patients from the IBM® MarketScan® Commercial and Medicare databases (2011-2019) who initiated rivaroxaban or warfarin after a diagnosis of NVAF, had ≥6 months of continuous health plan enrollment, had a CHA2DS2-VASc score ≥2, and had no history of stroke or anticoagulant use. Patient data were assessed until the earliest occurrence of a primary inpatient diagnosis of stroke, death, end of health plan enrollment, or end of study. Stroke severity was defined by National Institutes of Health Stroke Scale (NIHSS) score, imputed by random forest model. Cox proportional hazard regression was used to compare risk of stroke between cohorts, balanced by inverse probability of treatment weighting. RESULTS: The mean observation period from index date to either stroke, or end of eligibility or end of data was 28 months. Data from 13,599 rivaroxaban and 39,861 warfarin patients were included. Stroke occurred in 272 rivaroxaban-treated patients (0.97/100 person-years [PY]) and 1,303 warfarin-treated patients (1.32/100 PY). Rivaroxaban patients had lower risk for stroke overall (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.76-0.88) and for minor (NIHSS 1 to <5; HR, 0.83; 95% CI, 0.74-0.93), moderate (NIHSS 5 to <16; HR, 0.88; 95% CI, 0.78-0.99), and severe stroke (NIHSS 16 to 42; HR, 0.44; 95% CI, 0.22-0.91). CONCLUSIONS: The results of this study in a larger population of NVAF patients align with previous real-world findings and the ROCKET-AF trial by showing improved stroke prevention with rivaroxaban versus warfarin across all stroke severities.

Healthcare costs before and after stroke in patients with non-valvular atrial fibrillation who initiated treatment with rivaroxaban or warfarin.

AIMS: Rivaroxaban reduces stroke compared with warfarin in patients with non-valvular atrial fibrillation (NVAF). This study compared healthcare costs before and after stroke in NVAF patients treated with rivaroxaban or warfarin. MATERIALS AND METHODS: Using de-identified IBM MarketScan Commercial and Medicare databases, this retrospective cohort study (from 2011 to 2019) included patients with NVAF who initiated rivaroxaban or warfarin within 30 days after initial NVAF diagnosis. Patients who developed stroke were identified, and stroke severity was determined by the National Institutes of Health Stroke Scale (NIHSS) score, imputed by a random forest method. Total all-cause per-patient per-year (PPPY) costs of care were determined for patients: (1) who developed stroke during the pre- and post-stroke periods and (2) who remained stroke-free during the follow-up period. Treatment groups were balanced using inverse probability of treatment weighting. RESULTS: A total of 13,599 patients initiated rivaroxaban and 39,861 initiated warfarin, of which 272 (2.0%) and 1,303 (3.3%), respectively, developed stroke during a mean follow-up of 28 months. Among patients who developed stroke, PPPY costs increased from the pre-stroke to post-stroke period, with greater increases in the warfarin cohort relative to the rivaroxaban cohort. Overall, the costs increased by 1.78-fold for rivaroxaban vs 3.07-fold for warfarin; for less severe strokes (NIHSS < 5), costs increased 0.88-fold and 1.05-fold, respectively. Cost increases for more severe strokes (NIHSS ≥ 5) among rivaroxaban patients were half those for warfarin patients (3.19-fold vs 6.37-fold, respectively). Among patients without stroke, costs were similar during the follow-up period between the two treatment groups. CONCLUSIONS: Total all-cause costs of care increased in the post-stroke period, and particularly in the patients treated with warfarin relative to those treated with rivaroxaban. The lower rate of stroke in the rivaroxaban cohort suggests that greater pre- to post-stroke cost increases result from more strokes occurring in the warfarin cohort.

Effectiveness and safety of rivaroxaban versus warfarin in obese patients with acute venous thromboembolism: analysis of electronic health record data.

There is limited data evaluating clinical outcomes of rivaroxaban versus warfarin in obese patients with venous thromboembolism (VTE). Our objective was to evaluate the effectiveness and safety of rivaroxaban versus warfarin in obese VTE patients. We performed a cohort analysis using Optum® De-Identified Electronic Health Record data from 11/1/2012 to 9/30/2018. Patients with a body mass index (BMI) ≥ 30 kg/m2 admitted to the hospital, emergency department or observation unit for VTE, prescribed rivaroxaban or warfarin as their first oral anticoagulant (OAC) within 7-days and had ≥12-months of EHR activity prior were included. We excluded patients with OAC use at baseline or cancer. Patients were 1:1 matched (standard differences<0.10). Primary outcomes were recurrent VTE and major bleeding at 3-, 6- and 12-months using an intent-to-treat approach. Subanalyses of BMI 30.0-34.9, 35.0-39.9 and ≥ 40 kg/m2 were performed. Risk was compared using Cox regression and reported as hazard ratios (HRs) with 95% confidence intervals (CI). We identified 6755 rivaroxaban and 6755 warfarin users with BMI ≥ 30 kg/m2 and incident VTE. At 3-, 6- and 12-months, rivaroxaban was associated with a reduced hazard of recurrent VTE compared to warfarin (HR 0.61, 95%CI 0.51-0.72; HR 0.65, 95%CI 0.55-0.77; HR 0.63, 95%CI 0.54-0.74) with no difference in major bleeding (HR 0.99, 95%CI 0.68-1.44; HR 0.90, 95%CI 0.64-1.26; HR 1.00, 95%CI 0.73-1.36). No statistical difference was found across BMI categories for either recurrent VTE (p-interaction≥0.43) or major bleeding (p-interaction ≥ 0.58) at any time point. In obese VTE patients, prescription of rivaroxaban was associated with a significantly reduced risk of recurrent VTE versus warfarin, without impacting major bleeding. Our findings remained consistent across BMI classes.

Rivaroxaban Versus Warfarin for Management of Obese African Americans With Non-Valvular Atrial Fibrillation or Venous Thromboembolism: A Retrospective Cohort Analysis.

African Americans (AAs) and obese individuals have increased thrombotic risk. This study evaluated the effectiveness and safety of rivaroxaban versus warfarin in obese, AAs with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE). Optum® De-Identified Electronic Health Record (EHR) data was used to perform separate propensity-score matched analyses of adult, oral anticoagulant (OAC)-naïve AAs with NVAF or acute VTE, respectively; who had a body mass index≥30kg/m2 and ≥12-months EHR activity with ≥1-encounter before OAC initiation. Cox regression was performed and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). For the NVAF analysis, 1,969 rivaroxaban- and 1,969 warfarin-users were matched. Rivaroxaban was not associated with a difference in stroke/systemic embolism versus warfarin (HR = 0.88, 95%CI = 0.60-1.28), but less major bleeding (HR = 0.68, 95%CI = 0.50-0.94) was observed. Among 683 rivaroxaban-users with VTE, 1:1 matched to warfarin-users, rivaroxaban did not alter recurrent VTE (HR = 1.36, 95%CI = 0.79-2.34) or major bleeding (HR = 0.80, 95%CI = 0.37-1.71) risk versus warfarin at 6-months (similar findings observed at 3- and 12-months). Rivaroxaban appeared to be associated with similar thrombotic, and similar or lower major bleeding risk versus warfarin in these obese, AA cohorts.

Effectiveness and safety of rivaroxaban versus warfarin in obese nonvalvular atrial fibrillation patients: analysis of electronic health record data.

Background: Although rivaroxaban has demonstrated consistent drug levels in normal weight and obese patients, sufficient confirmation of equal clinical effectiveness and safety is currently lacking.Purpose: To evaluate the effectiveness and safety of rivaroxaban versus warfarin for prevention of stroke and systemic embolism (SSE) in obese nonvalvular atrial fibrillation (NVAF) patients.Methods: Using Optum de-identified Electronic Health Record (EHR) data from November 2011 to September 2018,we evaluated NVAF patients with a body mass index (BMI)≥30 kg/m2 newly initiated on rivaroxaban or warfarin (index date), with ≥12-months of EHR activity and ≥1 encounter before the index date. We excluded patients with valvular disease or evidence of oral anticoagulant (OAC) use at baseline. Patients who were prescribed rivaroxaban were 1:1 propensity-score matched to patients who were prescribed warfarin (standard differences <0.10 achieved for all covariates). Outcomes included SSE and major bleeding using an intent-to-treat approach. Subanalyses stratified by BMI (30.0-34.9, 35.0-39.9 and ≥40 kg/m2) were performed. Cox regression was performed and reported as hazard ratios (HRs) and 95% confidence intervals (CIs).Results: We included 35,613 rivaroxaban and 35,613 warfarin users with NVAF. Patients were followed for a median of 2.6 years (25%-75% range = 1.2-4.1). Rivaroxaban was associated with a reduced risk of SSE (HR = 0.83, 95%CI = 0.73-0.94) and major bleeding (HR = 0.82, 95%CI = 0.75-0.89) compared to warfarin. Subanalysis did not show a statistically significant interaction across BMI categories for SSE (p-interaction = .58) or major bleeding (p-interaction = .44) outcomes.Conclusions: Among obese NVAF patients, prescription of rivaroxaban was associated with a reduced risk of SSE and major bleeding compared to warfarin, which remained consistent across BMI classes.

Comparison of Healthcare Resource Utilization and Costs between Rivaroxaban and Warfarin for Nonvalvular Atrial Fibrillation in a Skilled Nursing Facility Setting.

BACKGROUND: Use of direct-acting oral anticoagulants for patients with nonvalvular atrial fibrillation (NVAF) in skilled nursing facilities (SNFs) is increasing. Rivaroxaban is commonly used in this setting as an alternative to warfarin, based on comparable or increased efficacy in preventing stroke and a similar or lower risk of major bleeding. OBJECTIVE: The aim of this study was to compare healthcare resource utilization (HCRU) and costs between NVAF patients receiving rivaroxaban or warfarin in SNFs. METHODS: This retrospective study examined de-identified claims from Optum® Clinformatics® Extended Data Mart (1 January 2013-31 December 2017). Eligible patients had an AF diagnosis, were prescribed rivaroxaban or warfarin during an SNF stay, and had one or more such prescriptions filled in the 6 months preceding the stay. Patients were excluded if they received another oral anticoagulant or had evidence of valvular heart disease, mitral stenosis, or organ/tissue transplant. HCRU, mean number of events, and all-cause healthcare costs during the index SNF stay were reported. Results were also reported on a per-patient-per-month (PPPM) basis. Exploratory analyses at different time periods were also conducted. RESULTS: Overall, 4423 rivaroxaban patients and 22,796 warfarin patients were identified prior to inverse probability of treatment weighting adjustment. Index SNF stay was significantly shorter among rivaroxaban-treated patients (35.8 ± 35.8 days) versus warfarin (40.1 ± 46.3 days; p < 0.0001). During the SNF stay, overall HCRU was lower for the rivaroxaban cohort versus the warfarin cohort. All-cause total costs were significantly reduced for rivaroxaban ($6450 ± $10,379) versus warfarin ($7640 ± $16,556; p < 0.0001), and similar results were observed when calculated on a PPPM basis. During the 1-year post-index period, PPPM all-cause total costs were significantly lower with rivaroxaban versus warfarin ($4135 vs. $4561; p < 0.0001). CONCLUSION: In this SNF setting, HCRU and costs were lower among patients with NVAF who were experienced users of rivaroxaban compared with those who were experienced users of warfarin. These findings may help inform clinical decision making to reduce the economic burden of NVAF among older adults in SNFs.

Healthcare resource utilization and costs among nonvalvular atrial fibrillation patients initiating rivaroxaban or warfarin in skilled nursing facilities: a retrospective cohort study.

Objective: Atrial fibrillation (AF) is present in up to 17% of patients in skilled nursing facilities (SNFs). This study compared healthcare resource utilization (HRU) and costs between AF patients initiating rivaroxaban or warfarin in SNFs.Methods: Using de-identified claims from Optum Clinformatics Extended Data Mart (1 January 2013 to 31 December 2017), this retrospective cohort study indexed AF patients with first SNF admission during which rivaroxaban or warfarin was initiated within 3 days of admission. To adjust for selection bias, inverse probability of treatment weighting (IPTW) was applied for baseline characteristics. Logistic regression and generalized linear models were used to compare HRU and costs.Results: 519 rivaroxaban and 1129 warfarin patients met inclusion criteria. After IPTW, the cohorts were well balanced for baseline characteristics. The average length of index SNF stay was 32.07 and 37.44 days for rivaroxaban and warfarin patients, respectively. During SNF stay, rivaroxaban patients had 27% lower odds of hospitalization (p < .0001), 2.7 fewer international normalized ratio (INR) tests per-patient-per-month (PPPM; p < .001), and 2.3 fewer pathology/laboratory encounters PPPM (p < .0001) than warfarin patients. All-cause healthcare costs were $2638 lower with rivaroxaban versus warfarin (p < .0001) during the index SNF stay, with lower medical costs (p < .0001) but higher pharmacy costs (p < .0001). Total all-cause healthcare costs 100 days post-index SNF were $8746 lower with rivaroxaban versus warfarin (p < .0001).Conclusions: In the SNF setting, AF patients treated with rivaroxaban had 5-day shorter length of stay, lower HRU, and lower all-cause total and medical costs compared to warfarin, despite higher treatment costs. These findings may help inform clinical decision-making to reduce economic burden.

Effectiveness and safety of anticoagulants for the treatment of venous thromboembolism in patients with cancer.

Anticoagulation is used to treat venous thromboembolism (VTE) in cancer patients, but may be associated with an increased risk of bleeding. VTE recurrence and major bleeding were assessed in cancer patients treated for VTE with the most currently prescribed anticoagulants in clinical practice. Newly diagnosed cancer patients (first VTE 1/1/2013-05/31/2015) who initiated rivaroxaban, low-molecular-weight heparin (LMWH), or warfarin were identified from Humana claims data and observed until end of eligibility or end of data availability. VTE recurrence was a hospitalization with a primary diagnosis of VTE ≥7 days after first VTE. Major bleeding events on treatment were identified using validated criteria. Cohorts were compared using Kaplan-Meier rates at 6 and 12 months and Cox proportional hazards models. Cohorts were adjusted for their differences at baseline. A total of 2428 patients (rivaroxaban: 707; LMWH: 660; warfarin: 1061) met inclusion criteria. Patient characteristics were well balanced after weighting. There was a trend for lower VTE recurrence rates in rivaroxaban users compared to LMWH users at 6 months (13.2% vs. 17.1%; P = .060) and significantly lower at 12 months (16.5% vs. 22.2%; P = .030) [HR: 0.72, 95% CI: (0.52-0.95); P = .024]. VTE recurrence rates were also lower for rivaroxaban than warfarin users at 6 months (13.2% vs. 17.5%; P = .014) and 12 months (15.7% vs. 19.9%; P = .017) [HR: 0.74, 95% CI: (0.56-0.96); P = .028]. Major bleeding rates were similar across cohorts. This real-world analysis suggests cancer patients with VTE treated with rivaroxaban had significantly lower risk of recurrent VTE and similar risk of bleeding compared to those treated with LMWH or warfarin.

Healthcare costs associated with rivaroxaban or warfarin use for the treatment of venous thromboembolism.

INTRODUCTION: Rivaroxaban has been shown to have similar efficacy but less major bleeding than warfarin in randomized trials of patients experiencing venous thromboembolism (VTE). This report sought to assess healthcare costs up to 12-months following an index VTE in patients prescribed either rivaroxaban or warfarin. MATERIALS AND METHODS: This study analyzed claims from the MarketScan Commercial Claims and Encounters Database from November 2011-July 2015. It selected adults newly-diagnosed with VTE (deep vein thrombosis [DVT] or pulmonary embolism [PE]) if they had an outpatient prescription claim for rivaroxaban or warfarin within 7-days of the index event. Warfarin users were 2:1 propensity-score matched to rivaroxaban users and followed until the end of insurance coverage, end of data availability or 12-months of follow-up. Total per patient healthcare costs, including inpatient, outpatient, and overall pharmacy costs, were compared using a multivariable generalized linear model. RESULTS: In total, 10,929 rivaroxaban patients were matched to 21,858 warfarin patients. Mean follow-up for rivaroxaban and warfarin patients was 317- and 321-days for those experiencing an index DVT, and 313- and 318-days for those with PE. Mean overall treatment costs per patient were lower for rivaroxaban vs warfarin users (-$1,116, p = .0016). This cost difference was driven by lower inpatient (-$622) and outpatient (-$1,156) treatment costs, and the higher pharmacy costs ($661) were, therefore, fully offset. Results were similar when analysis was restricted to DVT patients. No significant difference in total costs was observed in patients experiencing an index PE. LIMITATIONS: Claims databases are subject to inaccuracies and missing data. Prescription claims may not fully reflect actual medication utilization. Despite propensity-score matching and regression, residual confounding cannot be excluded. CONCLUSIONS: Rivaroxaban was associated with significantly lower total per patient VTE treatment costs, despite higher pharmacy costs. These savings are the result of decreased inpatient and outpatient healthcare utilization costs associated with rivaroxaban.