Rivaroxaban Cohort Research Articles

Abstract 4137535: Gastrointestinal Bleeding Risk: Diltiazem versus Metoprolol in Patients on Rivaroxaban, Apixaban, or Dabigatran.

Introduction: A recent JAMA study by Ray et al., reported severe bleeding risk among older adults with atrial fibrillation (Afib) receiving apixaban or rivaroxaban along with diltiazem compared to metoprolol. Our investigation extended to evaluating the gastrointestinal (GI) bleeding risk associated with various Xa inhibitors and dabigatran when combined with either diltiazem, or metoprolol among all adults ages 18 and older. Method: We conducted a comparative retrospective cohort study using de-identified patient data obtained from the global network of the TriNetX platform, a comprehensive electronic health records system comprising 120 healthcare systems and more than 147 million patients worldwide. The cohorts were divided into patients treated with diltiazem vs. metoprolol while receiving apixaban or rivaroxaban (Cohort A), patients receiving metoprolol with apixaban vs. rivaroxaban treatment (Cohort B), patients treated with diltiazem with apixaban vs rivaroxaban (Cohort C), and patients treated with diltiazem vs metoprolol who received dabigatran (Cohort D). The risk of gastrointestinal hemorrhage among the cohorts was evaluated. Propensity score matching was employed to balance baseline characteristics between the cohorts, including age, sex, ethnicity, and comorbidities. Results: The risk of GI bleed in patients taking diltiazem with either apixaban or rivaroxaban was 6.3%, while the risk in patients taking metoprolol with either of these Xa inhibitors was 5.7 % (p< 0.0001, 95%CI (1.074,1.111), RR 1.09. In patients taking metoprolol with apixaban, GI bleed risk was 5.4%, compared to 6.4% in those taking metoprolol with rivaroxaban (p< 0.0001, 95% CI (0.838, 0.868), RR 0.85. For patients taking diltiazem with rivaroxaban, GI bleed risk was 7.3%, whereas it was 5.8% in those taking diltiazem with apixaban (p< 0.0001, 95% CI (1.194, 1.265), RR 1.23. Risk of GI bleed in patients taking diltiazem with dabigatran was 7.4%% while it was 6.71% for patients treated with metoprolol and dabigatran (p< 0.0011, CI 95% (1.038,1.16), RR 1.097) Discussion: Global patients’ data in this study suggested similar findings reported by Ray et al. Additionally, among all ages adults with Afib, treatment with metoprolol and apixaban was associated with the lower risk of GI bleed when compared with metoprolol and rivaroxaban. While the highest risk of GI bleed was associated with concurrent diltiazem and dabigatran use.

Gender and racial differences in outcomes among patients with NVAF treated with oral anticoagulants: a real-world evaluation of Medicare beneficiaries

Abstract Introduction Anticoagulation therapies are essential component of disease management for patients with atrial fibrillation (AF). Direct-acting oral anticoagulants (DOACs), such as apixaban, rivaroxaban, and dabigatran have shown greater benefit in reducing stroke/systemic embolism (SE) and bleeding risk compared to warfarin. However, few studies have assessed whether the beneficial effects of DOACs are consistent across gender and race. Purpose To assess the association between apixaban use and the risk of stroke/SE and major bleeding (MB) compared to warfarin, rivaroxaban, and dabigatran; and to determine whether the associations differ by gender and race. Methods Adult patients with AF diagnosis who initiated warfarin or a DOAC between January 1, 2013 and December 31, 2019 were identified using Medicare claims databases. Patients were classified into warfarin, apixaban, dabigatran, or rivaroxaban cohorts based on index prescription. Inverse Probability Treatment Weighting Cox proportional hazard models were used to assess the association between DOAC therapy initiation and risk of stroke/SE and MB, overall and among gender and race. Results Among a total of 1,079,540 included patients, 486,257 (45.04%) were in the apixaban cohort, 46,920 (4.35%) in the dabigatran cohort, 267,991 (24.82%) in the rivaroxaban cohort, and 278,372 (25.79%) in the warfarin cohort. Overall, the risks of stroke/SE and MB were lower for apixaban when compared with warfarin (stroke/SE: HR: 0.69 [95% confidence interval (CI): 0.65-0.74], MB: 0.59 [95% CI: 0.57-0.60]), rivaroxaban (stroke/SE: 0.88 [95% CI: 0.84-0.92], MB: 0.60 [95% CI: 0.58-0.61]) and dabigatran(stroke/SE: 0.88 [95% CI: 0.80-0.95], MB: 0.76 [95% CI: 0.72-0.80]). Among 140,587 females, the risk was lower for apixaban as compared with warfarin (stroke/SE: 0.72 [95% CI: 0.67-0.78], MB: 0.60 [95% CI: 0.58-0.62]) and rivaroxaban (stroke/SE: 0.88 [95% CI: 0.83-0.93], MB: 0.59 [95% CI: 0.57-0.61]), but similar risk of stroke/SE was noted for apixaban compared to dabigatran (stroke/SE: 0.98 [95% CI: 0.86-1.11]). Among 137,785 males, the risk of stroke/SE and MB were lower for apixaban compared with warfarin, rivaroxaban, and dabigatran. Among 16,288 Black patients, the risk was lower for apixaban as compared with warfarin (stroke/SE: 0.72 [95% CI: 0.63-0.83] MB: 0.59 [95% CI: 0.54-0.65]), also lower risk of MB was noted for apixaban as compared with rivaroxaban (MB: 0.56 [95% CI: 0.5-0.62]), but a similar risk of stroke/SE was noted compared to rivaroxaban and dabigatran, and similar risk of MB was noted compared to dabigatran. Among 247,642 White patients, the risk of stroke/SE and MB were lower for apixaban compared with warfarin, rivaroxaban, and dabigatran. All the results along with comparisons are displayed in the accompanying figures. Conclusion Apixaban demonstrated lower risk of stroke/SE and major bleeding when compared to warfarin, rivaroxaban, and dabigatran across most race and gender subgroups.Figure 1_Risk of stroke/SEFigure 2_Risk of Major Bleeding

Safety and effectiveness of rivaroxaban for prevention of stroke in patients with nonvalvular atrial fibrillation: analysis of routine clinical data from four countries

ABSTRACT Background The safety and effectiveness of rivaroxaban versus vitamin K antagonists (standard of care [SOC]) for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) was evaluated in Europe. Research design and methods Observational studies were conducted in the UK, the Netherlands, Germany, and Sweden. Primary safety outcomes were hospitalization for intracranial hemorrhage, gastrointestinal bleeding, or urogenital bleeding among new users of rivaroxaban and SOC with NVAF; outcomes were analyzed using cohort (rivaroxaban or SOC use) and nested case–control designs (current vs nonuse). Statistical analyses comparing rivaroxaban and SOC cohorts were not performed. Results Overall, 162,919 rivaroxaban users and 177,758 SOC users were identified. In the cohort analysis, incidence ranges for rivaroxaban users were 0.25–0.63 events per 100 person-years for intracranial bleeding, 0.49–1.72 for gastrointestinal bleeding, and 0.27–0.54 for urogenital bleeding. Corresponding ranges for SOC users were 0.30–0.80, 0.30–1.42, and 0.24–0.42, respectively. In the nested case–control analysis, current SOC use generally presented a greater risk of bleeding outcomes than nonuse. Rivaroxaban use (vs nonuse) was associated with a higher risk of gastrointestinal bleeding, but a similar risk of intracranial or urogenital bleeding, in most countries. Ischemic stroke incidence ranged from 0.31 to 1.52 events per 100 person-years for rivaroxaban users. Conclusions Incidences of intracranial bleeding were generally lower with rivaroxaban than with SOC, whereas incidences of gastrointestinal and urogenital bleeding were generally higher. The safety profile of rivaroxaban for NVAF in routine practice is consistent with findings from randomized controlled trials and other studies.

Healthcare Resource Utilization and Costs of Rivaroxaban Versus Warfarin Among Non-valvular Atrial Fibrillation (NVAF) Patients with Diabetes in a US Population.

The healthcare resource utilization (HRU) and costs of oral anticoagulant-naïve patients with non-valvular atrial fibrillation (NVAF) and diabetes initiated on rivaroxaban or warfarin in the United States (US) has not been previously evaluated. This retrospective study used data from the Optum's de-identified Clinformatics® Data Mart Database (1 January, 2012 to 30 September, 2021) to evaluate the HRU and costs of adult patients with NVAF and diabetes newly initiated on rivaroxaban or warfarin (on or after January 2013). Inverse probability of treatment weighting (IPTW) was used to adjust for confounding between cohorts. HRU and costs (USD 2021) were assessed per patient-year (PPY) post-treatment initiation. Weighted cohorts were compared using rate ratios (RR) from Poisson regression models, odds ratios (OR) from logistic regression models, and cost differences; 95% confidence intervals (CI) and p values were generated using non-parametric bootstrap procedures. After IPTW, 17,881 and 19,274 patients initiated on rivaroxaban and warfarin were included, respectively (mean age: 73years; 40% female). During 12months of follow-up, the rivaroxaban cohort had lower all-cause HRU PPY across all components, including lower rates of inpatient stays (RR: 0.84, 95% CI 0.81, 0.88), outpatient visits (RR: 0.67, 95% CI 0.66, 0.68), and 30day hospital readmission (OR: 0.75, 95% CI 0.66, 0.83; all p<0.001) compared to the warfarin cohort. Moreover, rivaroxaban was associated with medical cost savings PPY (mean cost difference: -$9306, 95% CI -$11,769, -$6607), which compensated for higher pharmacy costs relative to warfarin (mean cost difference: $5518, 95% CI $5193, $5839), resulting in significantly lower all-cause total healthcare costs for rivaroxaban versus warfarin (mean cost difference: -$3788, 95% CI -$6258, -$1035; all p<0.001). Among NVAF patients with diabetes in a real-world US setting, rivaroxaban was associated with lower healthcare costs compared to warfarin.

Clinical and Economic Outcomes in Low-risk Pulmonary Embolism Patients Treated with Rivaroxaban versus Standard of Care

BackgroundL Rivaroxaban, a fixed-dose oral direct factor Xa inhibitor, does not require continuous monitoring and thus reduces the hospital stay and economic burden in low-risk pulmonary embolism (LRPE) patients. Study Question: What is the effectiveness of rivaroxaban versus the standard of care (SOC; low-molecular-weight heparin, unfractionated heparin, warfarin) among LRPE patients in the Veterans Health Administration? Study Design: Adult patients with continuous health plan enrollment for ≥12 months pre- and 3 months post-inpatient PE diagnosis (index date=discharge date) between October 1, 2011- June 30, 2015 and an anticoagulant claim during the index hospitalization were included. Measures and Outcomes Patients scoring 0 points on the simplified Pulmonary Embolism Stratification Index were considered low-risk and were stratified into SOC and rivaroxaban cohorts. Propensity score matching (PSM) was used to compare hospital-acquired complications (HACs), PE-related outcomes (recurrent venous thromboembolism, major bleeding, and death), and healthcare utilization and costs between the rivaroxaban and SOC cohorts. Results: Among 6746 PE patients, 1918 were low-risk; of these, 73 were prescribed rivaroxaban, 1546 were prescribed SOC, and 299 were prescribed other anticoagulants during the index hospitalization. After 1:3 PSM, 64 rivaroxaban and 192 SOC patients were included. During the index hospitalization, rivaroxaban users (versus SOC) had similar inpatient length of stay (LOS; 7.0 vs 6.7 days, standardized difference [STD]=1.8) but fewer HACs (4.7% vs 10.4%; STD: 21.7). In the 90-day post-discharge period, PE-related outcome rates were similar between the cohorts (all p&gt;0.05). However, rivaroxaban users had fewer outpatient (15.9 vs 20.4; p=0.0002) visits per patient as well as lower inpatient ($765 vs $2,655; p&lt;0.0001), pharmacy ($711 vs $1,086; p=0.0033), and total costs ($6,270 vs $9,671; p=0.0027). Conclusions: LRPE patients prescribed rivaroxaban had similar index LOS and PE-related outcomes, but fewer HACs, and lower total costs than those prescribed SOC.

Effectiveness, safety, and healthcare costs associated with rivaroxaban versus warfarin among venous thromboembolism patients with obesity: a real-world study in the United States

Prior observational studies suggest rivaroxaban is safe and effective among patients with morbid obesity who suffered a venous thromboembolism (VTE) event, but existing data are more limited in the broader population of VTE patients with obesity. This study assessed VTE recurrence, major bleeding, healthcare resource utilization, and healthcare costs among VTE patients with obesity who received rivaroxaban versus warfarin. VTE patients with obesity who initiated rivaroxaban or warfarin after a first VTE (index date) were identified from the IQVIA PharMetrics® Plus database (01/02/2011–09/30/2019). The follow-up period spanned from the index date until health plan disenrollment, end of data availability, cancer diagnosis/treatment, end of the 12 month post-index period, or (for the analysis of major bleeding) anticoagulant discontinuation or switch. Patient characteristics were balanced using inverse probability of treatment weighting. The weighted rivaroxaban (N = 8666) and warfarin cohorts (N = 5946) were well balanced (mean age = 51 years, females = 52%). Over a 9.6 months mean observation period, rivaroxaban users had a significantly lower risk of VTE recurrence [7.0% vs. 8.2%, HR(95% CI) = 0.85(0.75;0.97)] and a similar risk of major bleeding [4.1% vs. 3.6%, HR(95% CI) = 1.11(0.89;1.37)] relative to warfarin users at 12 months. Relative to warfarin users, rivaroxaban users had significantly fewer all-cause outpatient visits [RR(95% CI) = 0.71(0.70;0.74)]. The higher pharmacy costs incurred by rivaroxaban recipients (cost difference = $1252) were offset by lower medical costs (cost difference = − $2515, all p < 0.05) compared with warfarin recipients. Our findings suggest that rivaroxaban is safe and effective versus warfarin, and associated with lower medical costs among VTE patients with obesity.

MO638: Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Obesity, Type Two Diabetes, CKD

Abstract BACKGROUND AND AIMS We aimed to estimate the clinical characteristics and outcomes of rivaroxaban and warfarin in patients with nonvalvular atrial fibrillation (NVAF) and concurrent obesity, type two diabetes (T2D) and chronic kidney disease (CKD). METHOD A multicenter prospective cohort study, where consecutive eligible rivaroxaban or warfarin treated patients with NVAF concurrent obesity, T2D and CKD, were registered. Patients were also required to be ≥18 years of age, and have obesity, which was defined as BMI ≥30 kg/m2 diabetes and CKD. Patients were followed-up for clinical events over a mean period of 1 year. Primary outcome was a composite of 1-year mortality, stroke or systemic embolism, major bleeding and myocardial infarction, end-stage kidney disease, while secondary outcomes included those components separated. Treatment cohorts were matched using propensity scores and were compared for stroke/systemic embolism (SE) and major bleeding using Cox proportional hazards models. RESULTS A total of 194 (n = 103, rivaroxaban; n = 91, warfarin) matched pairs of NVAF patients with obesity, T2D and CKD who initiated treatment with rivaroxaban or warfarin were included. Prior to matching, rivaroxaban patients were younger than warfarin patients (mean age, 67.9 versus 69.2 years) and had lower mean scores for the QCI, CHA2DS2-VASc and HAS-BLED. In the intent-to-treat analysis, patients receiving rivaroxaban had a significant 19% reduction in the composite risk of stroke or SE compared with those receiving warfarin [HR 0.85 (95% CI 0.77–0.90)]. The risk of each component of the composite outcome was lower in the rivaroxaban cohort versus the warfarin cohort with significant differences for ischemic stroke and hemorrhagic stroke. The difference in SE was not statistically significant. Outcome rates were lower in the as-treated sensitivity analysis, with significant reductions in the composite outcome of stroke/SE risk observed for rivaroxaban versus warfarin [HR 0.70 (95% CI 0.61–0.80)]. Ischemic stroke and hemorrhagic stroke risks were also significantly lower with rivaroxaban versus warfarin in the as-treated sensitivity analysis. The risk of major bleeding was similar between the rivaroxaban cohort and the warfarin cohort [HR 0.91 (95% CI 0.79–1.06)]. CONCLUSION In NVAF patients with comorbidities of obesity, T2D and CKD, who initiated rivaroxaban had a significantly lower risk of stroke/SE compared with patients initiating warfarin. The risk of major bleeding was not significantly different between treatment groups. Patients receiving rivaroxaban had a significantly higher rate of adherence to treatment, supporting the use of rivaroxaban as an alternative to warfarin in NVAF patients with comorbidities of obesity, T2D and CKD.

Effectiveness and Safety of Rivaroxaban versus Warfarin Among Nonvalvular Atrial Fibrillation Patients with Obesity and Polypharmacy.

BackgroundCurrent evidence suggests that rivaroxaban may be well tolerated and effective in patients with nonvalvular atrial fibrillation (NVAF) and obesity; however, there is limited evidence on the impact of polypharmacy in this population. This study evaluated real-world clinical outcomes with rivaroxaban versus warfarin in patients with NVAF and obesity according to the number of concurrent medications.MethodsThis retrospective cohort study identified patients with one or more pharmacy claim for rivaroxaban or warfarin from two large claims databases. Patients were required to have an atrial fibrillation diagnosis, body mass index ≥ 30 kg/m2 and the presence of polypharmacy (1–4, 5–9, or ≥ 10 concurrent medications). Outcomes of stroke, systemic embolism, and major bleeding were compared between the rivaroxaban and warfarin cohorts after propensity score matching (PSM).ResultsA total of 95,875 patients were identified with one or more claim for either rivaroxaban or warfarin. After PSM, patient characteristics were balanced between cohorts (n = 21,547 in each cohort). The overall composite risk of stroke and systemic embolism was significantly lower in the rivaroxaban cohort compared with the warfarin cohort (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.70–0.84; p < 0.001). The risks of ischemic stroke, hemorrhagic stroke, and systemic embolism separately were also significantly reduced with rivaroxaban. Major bleeding risk was similar between cohorts (HR 0.93, 95% CI 0.81–1.06; p = 0.2842), and results were consistent across the three polypharmacy groups.ConclusionsIn this real-world study of NVAF patients with obesity, rivaroxaban was associated with lower risks of stroke and systemic embolism and similar risk of major bleeding versus warfarin across polypharmacy categories.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40256-021-00520-7.

Safety of Direct Acting Oral Anticoagulants (DOACs) in Comparison to Low Molecular Weight Heparin (LWMH) in Gastrointestinal and Genito-Urinary Cancers

Introduction:DOACs are absorbed in the gastrointestinal (GI) tract and DOAC elimination is primarily through the GI and genitourinary (GU) systems. The safety of DOACs in cancer associated thrombosis in subjects with malignant lesions in GI and GU malignancies has been of concern. Studies have been sparse and data conflicting.Methods:We identified patients with active GI and GU malignancies from July 2001 to July 2020 with confirmed VTE at our institution. Patients who received either enoxaparin or a DOAC (apixaban or rivaroxaban) were included in the study. Demographic, disease characteristics, VTE data and events were extracted from electronic medical records (EMR). Date of anticoagulation (AC) initiation was based on the first order and/or prescription of the anticoagulant. Patients were followed either to the earliest bleeding event (BE) or one year from initiation, whichever occurred first. BEs were categorized based on ISTH guidelines. Variables were compared between LMWH and DOAC cohorts, as well as between the apixaban and rivaroxaban cohorts, using t-tests for continuous variables and chi-squared tests or Fisher's exact test for categorical variables.Results:We identified a total of 206 patients, 159 in the DOAC and 47 in the LWMH groups. Table 1 describes the baseline characteristics of the study populations. Median age of patients, gender and BMI were comparable for all groups. When evaluated for type of cancer, 66.6% of patients had active GI malignancy while 33.3% had active GU tumors. The majority of the patients given DOACs had a better ECOG status than those in the LMWH group (p=0.0023), but no difference was noted for ECOG status between DOACs (p=0.69). Most patients had metastatic disease. The majority of the VTE events were in the form of DVTs. Concomitant aspirin intake was 9.4% in DOAC and 4.2% in LMWH groups. Cancer subtypes and AC choice data are given in detail in Table 2.LMWH use was higher in blacks and somewhat lower in the Hispanic population (Table 1). When anticoagulation choice was examined by primary tumor site (Table 2), disproportionately more patients with GU tumors were placed on LMWH while more GI cancers were given a DOAC (p=0.014). Extent and stage of the cancer did not appear to bias anticoagulant choice (p=0.62). Within the DOACs, rivaroxaban use was higher in the GI cancers but considerably less used in the GU malignancies (p=0.00049).There was one recurrent thrombosis in each of the apixaban (1/86) and the rivaroxaban (1/73) cohorts. There were no recurrent events in the LMWH (0/47) cohort.The majority of patients in the DOAC and LMWH groups, 88.1% and 86.4%, had no CRNMB or major bleeding events in the 1-year period after the initiation of the therapeutic AC (Table 3). Combined BE (clinically relevant non-major bleeding [CRNMB] and major bleeding rates) with apixaban, rivaroxaban and LMWH were 17.4% (15/86), 20.5% (15/73), and 19.1% (9/47) respectively. There were no fatal bleeding episodes in any of the groups. Most of the bleeding events on DOACs and LMWHs occurred in the same organ system as the primary cancer (Table 3) but there was no statistically significant difference in bleeding events between patients on DOACs or LMWH for GI, GU or all cancer types (p=0.63, 0.75 and 0.97 respectively). Within DOACs, we also noted no statistically significant difference in the bleeding events with apixaban as compared to rivaroxaban in patients with GI primary, GU primary or all cancer types together, (p=0.47, 0.94 and 0.62 respectively).Conclusion:No significant differences in major/CRNM bleeding events were found for patients with GI or GU cancer associated thrombosis given DOACs (apixaban/rivaroxaban) vs enoxaparin. The tumor site is often the site of bleeding, but no differences in tumor-specific site bleeding could be shown by anticoagulant choice. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Effectiveness and safety of rivaroxaban versus warfarin among nonvalvular atrial fibrillation patients with obesity and diabetes.

To compare clinical outcomes of rivaroxaban and warfarin in patients with nonvalvular atrial fibrillation (NVAF) and concurrent obesity and diabetes. Patients aged ≥18years were identified from a healthcare claims database with the following criteria: newly initiating rivaroxaban or warfarin, ≥1 medical claim with a diagnosis of AF, obesity determined by validated machine learning algorithm, and≥1 claim with a diagnosis of diabetes or for antidiabetic medication. Treatment cohorts were matched using propensity scores and were compared for stroke/systemic embolism (SE) and major bleeding using Cox proportional hazards models. A total of 9999 matched pairs of NVAF patients with obesity and diabetes who initiated treatment with rivaroxaban or warfarin were included. The composite risk of stroke/SE was significantly lower in the rivaroxaban cohort compared with the warfarin cohort (HR 0.82; 95% CI 0.74-0.90). Risks of ischemic and hemorrhagic strokes were also significantly reduced with rivaroxaban versus warfarin, but not SE. Major bleeding risk was similar between treatment cohorts (HR 0.92; 95% CI 0.78-1.09). In NVAF patients with comorbidities of obesity and diabetes, rivaroxaban was associated with lower risks of stroke/SE and similar risk of major bleeding versus warfarin.

Healthcare Resource Utilization and Costs of Rivaroxaban Versus Warfarin Among Nonvalvular Atrial Fibrillation Patients with Obesity and Diabetes.

IntroductionNonvalvular atrial fibrillation (NVAF) is associated with a substantial economic burden, particularly in patients with comorbid conditions. This study compared healthcare resource utilization (HRU) and costs of rivaroxaban and warfarin in patients with NVAF, obesity, and diabetes.MethodsA de-identified healthcare claims database was used to identify adult patients newly initiating rivaroxaban or warfarin and having at least one medical claim with a diagnosis of AF, obesity determined by validated algorithm, and at least one claim with a diagnosis of diabetes or for antidiabetic medication from December 2011 to March 2020. Propensity score matching was used to balance the treatment cohorts on the basis of demographics and baseline characteristics. All-cause and NVAF-related HRU rates and costs were compared between treatments using rate ratios, and mean cost differences were calculated on a per patient per year (PPPY) basis.ResultsA total of 9999 matched pairs of patients with NVAF, obesity, and diabetes were identified in the rivaroxaban and warfarin cohorts. Rate ratios of all-cause HRU were significantly reduced with rivaroxaban versus warfarin in all healthcare settings evaluated, except emergency room visits. The greatest impact was on physician office visits followed by hospital outpatient and inpatient visits. NVAF-related HRU was significantly lower for rivaroxaban versus warfarin in all care settings. Consistent with these findings, the length of hospital stay was significantly reduced by approximately 4 days among all patients for both all-cause and NVAF-related hospitalizations in the rivaroxaban cohort compared with the warfarin cohort. Rivaroxaban was associated with reductions in all-cause total healthcare costs by more than $5000 PPPY and NVAF-related medical costs by approximately $1100 PPPY.ConclusionIn comparison with warfarin, rivaroxaban reduced HRU and costs, particularly hospital inpatient and outpatient visits and physician office visits, in patients with NVAF and comorbidities of obesity and diabetes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-021-01161-4.

Efficacy and safety of direct oral anticoagulants in morbidly obese patients with non-valvular atrial fibrillation: a systematic review and meta-analysis

Abstract Introduction Atrial fibrillation (AF) is the most common arrhythmia, with an estimated prevalence between 1–4%. On the other hand, obesity continued to be a prevalent health issue worldwide. Direct oral anticoagulants (DOACs) have been increasingly preferred over warfarin; however, The International Society of Thrombosis and Hemostasis (ISTH) recommended avoiding the use of DOACs in patients with a BMI &amp;gt;40 or weight &amp;gt;120 kg because of limited clinical data in these patients. In this meta-analysis, we aimed to evaluate the efficacy and safety of DOACs in morbidly obese patients with non-valvular AF. Method We performed a comprehensive literature search using multiple databases from database inception through January 2021, for all the studies that evaluated the efficacy and safety of DOACs in morbidly obese patients with non-valvular AF. The primary outcome of interest was stroke or systemic embolism (SSE) rate. The secondary outcome was major bleeding (MB). All meta-analyses were conducted using a random-effect model. Results A total of 10 studies including 89,494 morbidly obese patients (BMI &amp;gt;40 or weight &amp;gt;120 kg) with non-valvular AF on oral anticoagulation therapy (45427 on DOACs vs. 44067 on warfarin) were included in the final analysis. One included study was a randomized controlled trial (RCT), another study was a post hoc analysis of an RCT and the rest were retrospective cohort studies. The mean follow-up period was 1.8 years (range 8 months to 3.1 years). The SSE rate was significantly lower in DOACs group compared to warfarin group (odds ratio (OR): 0.71; 95% confidence interval (CI): 0.62, 0.81; p&amp;lt;0.0001; I2=0%). MB rate was also significantly lower in DOACs group compared to the warfarin group (OR 0.60, 95% CI 0.46–0.78, P&amp;lt;0.0001, I2=86%). Subgroup analysis in the rivaroxaban and apixaban AF cohort showed a statistically significant difference in SSE and MB event rates favoring both over warfarin therapy. Dabigatran showed non-inferiority to warfarin in SSE rate but superiority in the safety outcome. Conclusions Our meta-analysis demonstrated that DOACs are effective and safe when compared to warfarin in morbidly obese patients. However, more large scale randomized clinical trials are needed to further evaluate the efficacy and safety of DOACs compared to warfarin in this cohort of patients. Funding Acknowledgement Type of funding sources: None. Stroke and systemic embolism eventsMajor bleeding events

Healthcare Costs Associated with Venous Thromboembolism in Cancer Patients Treated with Anticoagulants

Introduction: Venous thromboembolism (VTE) is highly prevalent in patients with active cancer and is associated with higher healthcare costs. Although LMWH is currently recommended for the treatment of VTE in cancer patients, oral anticoagulants warfarin and rivaroxaban are commonly used for treatment. Recent evidence among Medicare cancer patients with VTE showed that rivaroxaban is associated with lower healthcare costs than LMWH and similar costs to warfarin. This study compares healthcare costs of cancer patients treated with rivaroxaban or warfarin and LMWH in younger patients from a commercial insurance claims database.Methods: Medical and pharmacy claims from the Truven Health Analytics MarketScan databases in 1/1/2013 - 9/30/2016 were analyzed. Newly diagnosed cancer patients aged ≥18 were selected if they had a first VTE (deep vein thrombosis (DVT) or pulmonary embolism (PE); excluding upper VTE) diagnosis occurring within 30 days prior to or any time after their first cancer diagnosis and ≥1 dispensing of an anticoagulant agent within 7 days after their VTE diagnosis. Based on the first anticoagulant agent received, patients were classified into one of the following cohorts: LMWH, warfarin, or rivaroxaban. The warfarin cohort included patients who started LMWH and warfarin within 7 days of their first VTE. Inverse probability of treatment weights (IPTW) based on propensity score were used to adjust for differences between treatment cohorts. Baseline characteristics were evaluated during the 6-month period prior to the index VTE. VTE-related costs were identified with a primary or secondary diagnosis of DVT or PE, and were evaluated for the entire follow-up period, starting from the initiation of the anticoagulant therapy until end of eligibility or end of data, whichever was earlier. Healthcare costs per-patient-per-year (PPPY) were evaluated and compared using mean cost differences (CD). Significance in cost differences between cohorts and 95% confidence intervals (CI) were estimated using nonparametric bootstrap procedures.Results: A total of 12,457 patients (LMWH: N=4,313; warfarin: N=4,774; rivaroxaban: N=3,370) were included. After weighting the cohorts, baseline demographic and clinical characteristics were well balanced. The mean age of patients ranged from 61.3 to 63.6 years and approximately half of all patients were women. Across cohorts, 25%-28% of patients were diagnosed with PE, 47%-48% were diagnosed with DVT, and 24%-27% were diagnosed with both PE and DVT. Between 71% and 76% of patients had their first VTE within one year of their cancer diagnosis. At first cancer diagnosis, 80%-82% of patients had solid tumors. The percent with cancers at high-risk for VTE (stomach, pancreas, brain) varied from 7%-14%. The mean Charlson comorbidity index ranged from 2.9-3.0. During the 6-month baseline period, healthcare costs were similar across cohorts. Over the follow-up period, patients treated with rivaroxaban had significantly lower VTE-related healthcare costs when compared with patients in the LMWH cohort (Table 1). VTE-related hospitalization, emergency room (ER) visit, outpatient visit, pharmacy, imaging, and other costs were all significantly lower for patients treated with rivaroxaban than for patients treated with LMWH (all P <0.03). VTE-related healthcare costs were $17,847 for the rivaroxaban cohort and $28,273 for the LMWH cohort (CD= -$10,426 [-$13,461; -$7,981]). VTE-related healthcare costs were similar between the rivaroxaban cohort and the warfarin cohort at $14,880 for the rivaroxaban cohort and $14,911 for the warfarin cohort (CD [95% CI] = -$32 [-$2,618; $2,417] (Table 1)). Higher VTE-related pharmacy costs in the rivaroxaban cohort (CD= $832 [$630; $1,082]) were offset by lower VTE-related outpatient visit costs (CD= -$1,370 [-$1,977; -$915]).Conclusion: This real-world analysis based on a commercial claims database showed that cancer patients treated with rivaroxaban after an initial VTE incurred significantly lower VTE-related healthcare costs than patients treated with LMWH and similar costs to patients treated with warfarin. [Display omitted] DisclosuresStreiff:CSL Behring: Consultancy, Research Funding; Janssen Scientific Affairs, LLC: Consultancy, Research Funding; Portola: Research Funding; Roche: Research Funding. Milentijevic:Janssen Scientific Affairs, LLC: Employment, Equity Ownership. McCormick:Janssen Scientific Affairs, LLC: Research Funding. Laliberté:Janssen Scientific Affairs, LLC: Research Funding. Crivera:Janssen Scientific Affairs, LLC: Employment, Equity Ownership. Lefebvre:Janssen Scientific Affairs, LLC: Research Funding. Lejeune:Janssen Scientific Affairs, LLC: Research Funding. Rozjabek:Janssen Scientific Affairs, LLC: Other: Fellowship supported by Janssen Scientific Affairs, LLC. Schein:Janssen Scientific Affairs, LLC: Employment, Equity Ownership, Other: Own in excess of $10,000 of J&J stock. Khorana:Pfizer: Consultancy, Honoraria; Halozyme: Consultancy, Honoraria; Janssen Scientific Affairs, LLC: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Amgen: Consultancy, Research Funding; Leo: Consultancy, Honoraria, Research Funding.

VTE Recurrence and Safety of Anticoagulants Among Patients with Cancer Treated for Venous Thromboembolism

Introduction:Anticoagulation (AC) is effective for the treatment of venous thromboembolism (VTE) in cancer patients, but is associated with an increased risk of bleeding. Currently, LMWH monotherapy is the recommended treatment for cancer patients with VTE; however, emerging data from Medicare patients suggests that rivaroxaban had a significantly lower risk of VTE recurrence and similar risk of major bleeding compared to LMWH or warfarin. In this study, we compared the effectiveness and risk of major bleeding associated with these anticoagulants in a younger cohort of patients from a commercial claims database.Methods: Truven Health Analytics MarketScan databases were used to find patients aged ≥18 newly diagnosed with cancer who then had their first VTE (deep vein thrombosis (DVT) or pulmonary embolism (PE); excluding upper VTE) between 1/1/2013 - 9/30/2016 and AC start ≤ 7 days. Patients were categorized into LMWH, warfarin, or rivaroxaban cohorts based on index AC. The warfarin cohort included patients who started LMWH and warfarin ≤ 7 days of their first VTE. Inverse probability of treatment weights based on propensity score were used to adjust for treatment differences in the comparison of LMWH vs. rivaroxaban, warfarin vs. rivaroxaban, and LMWH vs. warfarin. Patients were observed until the earliest of end of eligibility or data end. VTE recurrences were defined conservatively as hospitalizations with a primary diagnosis of VTE ≥7 days after the first VTE. Major bleeding events were identified using validated criteria (Cunningham et al., 2011) and evaluated while patients were on treatment. Kaplan-Meier rates at 6 and 12 months were used to compare VTE recurrence between cohorts. Time on treatment was approximately 30-50% of total eligibility time, so rates at 3 and 6 months were used to compare major bleeding between cohorts. Cox proportional hazard models were used to compare VTE recurrence and major bleeding risk between cohorts.Results: A total of 12,457 patients (LMWH: N=4,313; warfarin; N=4,774; rivaroxaban: N=3,370) were included. After weighting the cohorts, baseline demographic and clinical characteristics were well balanced. Mean patient age ranged from 61.3 to 63.6 years. Median observation time with LMWH was shorter than with rivaroxaban (6.8 vs. 8.3 months, p<0.001) and with warfarin (7.4 vs. 9.8 months, p<0.001). Time on treatment was significantly shorter as well (Figures 1A-1C). VTE recurrence rates were significantly lower with rivaroxaban than with LMWH users at 6 months (8.7% vs. 11.7%; p=0.003) and 12 months (11.9% vs.14.7%; p=0.006), respectively, with a hazard ratio (HR [95%CI]) of 0.83 (0.73-0.96; p=0.010; Figure 1A). Major bleeding rates for rivaroxaban and LMWH users were similar at 3 months (3.2% vs. 3.5%; p=0.592) and 6 months (4.4% vs. 4.9%; p=0.438), respectively [HR 0.91 (0.71-1.17; p=0.455]. VTE recurrence rates for rivaroxaban and warfarin users were similar at 6 months (8.2% vs 8.8%; p=0.530) and 12 months (11.3% vs 11.6%; p=0.675), respectively [HR 0.95 (0.83-1.09; p=0.456; Figure 1B)]. Major bleeding rates for rivaroxaban and warfarin users were also similar at 3 months (3.2% vs. 2.8%; p=0.199) and 6 months (4.2% vs. 3.8%; p=0.362), respectively [HR 1.08 (0.86-1.37; p=0.500)]. Recurrence rates were significantly lower for warfarin users than for LMWH users at 6 months (10.2% vs. 12.4%; p=0.006) and 12 months (13.3% vs. 15.3%; p=0.011), respectively, but the rate of recurrence over the entire follow up was not significantly different between the two cohorts [HR of 0.91 (0.81-1.02; p=0.103; Figure 1C)]. Major bleeding rates for warfarin and LMWH users were similar at 3 months (3.1% vs. 3.7%; p=0.114) and 6 months (4.3% vs. 5.1%; p=0.109), respectively [HR of 0.86 (0.68-1.08; p=0.187)].Conclusion: In this large cohort of cancer patients treated for VTE, time on treatment was shorter for patients treated with LMWH than oral agents. Rivaroxaban was associated with a significantly lower rate of VTE recurrence than LMWH and a similar rate of VTE recurrence to warfarin; major bleed rates were similar for all. While LMWH has been associated with greater reductions in recurrent VTE compared to warfarin in trials, poor persistence on LMWH in real world settings may explain its lack of comparative effectiveness in this analysis. [Display omitted] DisclosuresKhorana:Bayer: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Janssen Scientific Affairs, LLC: Consultancy, Honoraria, Research Funding; Leo: Consultancy, Honoraria, Research Funding; Halozyme: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Roche: Consultancy, Honoraria. Milentijevic:Janssen Scientific Affairs, LLC: Employment, Equity Ownership. McCormick:Janssen Scientific Affairs, LLC: Research Funding. Laliberté:Janssen Scientific Affairs, LLC: Research Funding. Crivera:Janssen Scientific Affairs, LLC: Employment, Equity Ownership. Lefebvre:Janssen Scientific Affairs, LLC: Research Funding. Lejeune:Janssen Scientific Affairs, LLC: Research Funding. Rozjabek:Janssen Scientific Affairs, LLC: Other: Fellowship supported by Janssen Scientific Affairs, LLC. Schein:Janssen Scientific Affairs, LLC: Employment, Equity Ownership, Other: Own in excess of $10,000 of J&J stock. Streiff:Roche: Research Funding; CSL Behring: Consultancy, Research Funding; Janssen Scientific Affairs, LLC: Consultancy, Research Funding; Portola: Research Funding.

Characterizing safety and efficacy in ovarian cancer patients with thromboembolism treated with rivaroxaban.

e18720 Background: There is a paucity of real-world data regarding rates of recurrent venous thromboembolism (VTE), major bleeding and all-cause mortality among ovarian cancer patients with thrombosis treated with direct oral anticoagulants (DOACs) currently available. We sought to evaluate the effectiveness and safety of rivaroxaban versus low molecular-weight heparin (LMWH) for cancer-associated thrombosis (CAT) treatment in patients with ovarian cancer. Methods: We utilized US Surveillance, Epidemiology and End Results-Medicare–linked data from 2013-2016 to identify adults with active ovarian cancer, undergoing hospitalization/emergency department admission for CAT and prescribed rivaroxaban or LMWH for outpatient anticoagulation. Rivaroxaban and LMWH cohorts were balanced using propensity score overlap weighting . Outcomes included the composite of recurrent thrombosis or major bleeding, each outcome separately and mortality at six-months using an intention-to-treat approach. On-treatment analysis after 12-months was also performed. Hazard ratios (HRs) with 95% confidence intervals using overlap weighted cox regression were reported. Results: We included 33 rivaroxaban and 92 LMWH-managed CAT patients. In each cohort, mean age was 73, 79.5% of patients were white, 46.9% had a history of ≥ stage 3 chronic kidney disease (CKD), two-thirds had metastatic disease at the time of VTE, and 32.6% had a prior VTE. Patients were diagnosed with ovarian cancer an average of 1.40 years prior to the index VTE event and 45.8% had a pulmonary embolism (with or without DVT) as the index event. Our analysis did not detect a significant difference in outcomes with rivaroxaban versus LMWH at six-months (Table). On-treatment analysis at 12-months showed similar results. Conclusions: Rivaroxaban may be a reasonable alternative to LMWH for CAT patients with ovarian cancer. Large observational studies are needed to confirm these results.[Table: see text]

Clinical and Economic Outcomes Among Nonvalvular Atrial Fibrillation Patients With Coronary Artery Disease and/or Peripheral Artery Disease

To address literature gaps on treatment with real-world evidence, this study compared effectiveness, safety, and cost outcomes in NVAF patients with coronary or peripheral artery disease (CAD, PAD) prescribed apixaban versus other oral anticoagulants. NVAF patients aged ≥65 years co-diagnosed with CAD/PAD initiating warfarin, apixaban, dabigatran, or rivaroxaban were selected from the US Medicare population (January 1, 2013 to September 30, 2015). Propensity score matching was used to match apixaban versus warfarin, dabigatran, and rivaroxaban cohorts. Cox models were used to evaluate the risk of stroke/systemic embolism (SE), major bleeding (MB), all-cause mortality, and a composite of stroke/myocardial infarction/all-cause mortality. Generalized linear and two-part models were used to compare stroke/SE, MB, and all-cause costs between cohorts. A total of 33,269 warfarin-apixaban, 9,335 dabigatran-apixaban, and 33,633 rivaroxaban-apixaban pairs were identified after matching. Compared with apixaban, stroke/SE risk was higher in warfarin (hazard ratio [HR]: 1.93; 95% confidence interval [CI]: 1.61 to 2.31), dabigatran (HR: 1.69; 95% CI: 1.18 to 2.43), and rivaroxaban (HR: 1.24; 95% CI: 1.01 to 1.51) patients. MB risk was higher in warfarin (HR: 1.67; 95% CI: 1.52 to 1.83), dabigatran (HR: 1.37; 95% CI: 1.13 to 1.68), and rivaroxaban (HR: 1.87; 95% CI: 1.71 to 2.05) patients vs apixaban. Stroke/SE- and MB-related medical costs per-patient per-month were higher in warfarin, dabigatran, and rivaroxaban patients versus apixaban. Total all-cause health care costs were higher in warfarin and rivaroxaban patients compared with apixaban patients. In conclusion, compared with apixaban, patients on dabigatran, rivaroxaban, or warfarin had a higher risk of stroke/SE, MB, and event-related costs.

Healthcare resource utilization and costs of rivaroxaban versus warfarin among non-valvular atrial fibrillation (NVAF) patients with obesity in a US population

Aim To assess the real-world healthcare resource utilization (HRU) and costs of patients with non-valvular atrial fibrillation (NVAF) and obesity newly initiated on rivaroxaban or warfarin in the US. Methods This retrospective study used IQVIA PharMetrics Plus data (01/2010–09/2019) to evaluate patients (≥18 years) with NVAF and obesity (body mass index ≥30 kg/m2) initiated on rivaroxaban or warfarin (on or after 01/2013). Inverse probability of treatment weighting (IPTW) was used to adjust for confounding between cohorts. HRU and costs were assessed post-treatment initiation. Weighted cohorts were compared using Poisson regression models and cost differences, with 95% confidence intervals (CIs) and p values generated using non-parametric bootstrap procedures. Results After IPTW, 10,555 and 5,080 patients were initiated on rivaroxaban and warfarin, respectively (mean age: 59 years). At 12 months follow-up, the rivaroxaban cohort had lower all-cause HRU, including fewer hospitalizations (rate ratio [RR]: 0.80, 95% CI: 0.74, 0.87), emergency room visits (RR: 0.89, 95% CI: 0.83, 0.97), and outpatient visits (RR: 0.72, 95% CI: 0.69, 0.77; all p < .05). Medical costs were also reduced in the rivaroxaban cohort (mean difference: −$6,759, 95% CI: −$9,814, −$3,311) due to reduced hospitalization costs (mean difference: −$5,967, 95% CI: −$8,721, −$3,327), resulting in lower total all-cause healthcare costs compared to the warfarin cohort (mean difference: −$4,579, 95% CI: −$7,609, −$1,052; all p < .05). The rivaroxaban cohort also had lower NVAF-related HRU and medical costs driven by lower hospitalization at 12 months post-treatment initiation. HRU and cost reductions associated with rivaroxaban persisted up to 36 months of follow-up. Limitations Claims data may have contained inaccuracies and obesity was classified based on ICD diagnosis codes given that patient BMI values were not available. Conclusions Rivaroxaban was associated with reduced HRU and costs compared to warfarin among NVAF patients with obesity in a real-world US setting.

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.

Long-term efficacy and safety of anticoagulation after atrial fibrillation ablation: data from the JACRE registry

BackgroundCatheter ablation (CA) is an important strategy for managing atrial fibrillation (AF). However, long-term anticoagulation strategies and clinical outcomes following CA, including thromboembolism and bleeding, have not yet been elucidated. MethodsWe established a prospective registry, called the JACRE registry, for patients on rivaroxaban or warfarin administration who received CA for AF. The outcomes up to 30 days following the procedure were reported previously. The present study involved longer follow-up of patients enrolled in this registry to evaluate long-term anticoagulation strategies and clinical outcomes. ResultsData of 975 patients (rivaroxaban, n = 823; warfarin, n = 152) were collected from 27 institutes. Patient population had mean age 63.7 ± 10.3 years, 710 (72.8%) males, mean CHA2DS2-VASc score 1.9 ± 1.5, and mean follow-up period 28.7 ± 12.7 months after the index procedure. Anticoagulants were continued in 496 (50.9%) patients during the follow-up. Thromboembolism occurred in 3 patients, hemorrhagic stroke in 5, and major bleeding events in 9 (annualized event rate, 0.13%, 0.22%, and 0.40% per patient-year, respectively). There were no differences in the composite event rate of thromboembolism and International Society on Thrombosis and Haemostasis major bleeding between rivaroxaban and warfarin cohorts (0.53% and 0.55% per patient-year, respectively). ConclusionsLong-term incidence of thromboembolism was extremely low in patients with AF treated with CA, while that of major bleeding was not especially low.Clinical Trials Registry: UMIN000032829 / UMIN000032830

Comparison of Anti-factor Xa Activity Among Three Different Factor Xa Inhibitors in Non-valvular Atrial Fibrillation Patients with Renal Impairment.

Factor-Xa inhibitors (FXaIs) are widely used for the treatment of non-valvular atrial fibrillation (NVAF). Although we have previously reported the distribution of the anti-factor Xa activity (AXA) values of three different FXaIs in NVAF patients, the differences in the distribution of AXA values among the different FXaIs in patients with renal impairment (RI) have not been fully elucidated. Trough and peak AXA values were measured in 94 patients taking rivaroxaban, 124 patients taking apixaban, and 66 patients taking edoxaban. Of them, we identified 26 patients with moderate RI [creatinine clearance (CrCl) 30-49mL/min] and 17 patients with severe RI (CrCl 15-29mL/min) in the rivaroxaban cohort, 37 patients with moderate RI and 17 patients with severe RI in the apixaban cohort, and 21 patients with moderate RI and 9 patients with severe RI in the edoxaban cohort. AXA values were measured using chromogenic AXA assays. Both trough and peak AXA values were compared between patients with moderate RI and those with severe RI in each cohort, and differences in the peak-to-trough ratio among the different drugs were assessed. In the rivaroxaban cohort, the peak AXA value was significantly higher in patients with severe RI than in those with moderate RI. In the apixaban cohort, neither the trough nor peak AXA values significantly differed between patients with moderate RI and those with severe RI. In the edoxaban cohort, the trough AXA value was significantly higher in patients with severe RI than in those with moderate RI, and peak AXA tended to be higher in patients with severe RI. The peak-to-trough ratio of AXA values was significantly lower in patients taking apixaban than in those taking rivaroxaban and edoxaban. Among Japanese NVAF patients with RI, the peak or trough AXA values were higher in patients with severe RI than in those with moderate RI when taking rivaroxaban and edoxaban, whereas both the peak and trough AXA values were similar between patients with severe RI and those with moderate RI when taking apixaban. The peak-to-trough ratio of AXA values was the lowest in patients taking apixaban.