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.

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 in patients with nonvalvular atrial fibrillation and stage IV-V chronic kidney disease.

BACKGROUND: There is limited evidence on the effectiveness and safety of direct-acting oral anticoagulants in patients with nonvalvular atrial fibrillation (NVAF) and advanced chronic kidney disease (CKD). This study compared the risks of ischemic stroke/systemic embolism (ISSE) and major bleeding in patients with NVAF and stage IV-V CKD treated with rivaroxaban or warfarin. METHODS: Patients with NVAF and stage IV-V CKD who initiated rivaroxaban or warfarin treatment between November 2011 and June 2018 were selected from the Optum® Deidentified Electronic Health Record Database. Propensity score matching was used to balance rivaroxaban and warfarin patients on 112 measured baseline covariates. ISSE and major bleeding events over 2 years following treatment initiation were ascertained with validated end point definitions. Outcomes were analyzed as time-to-event data using Kaplan-Meier survival estimators and Cox regression. RESULTS: A total of 781 eligible rivaroxaban-treated patients were propensity score-matched to 1,536 warfarin-treated patients; baseline covariates were well balanced after matching (absolute standardized differences <0.1). The average patient age was 80 years; 60.5% were female; 81.3% and 18.7% had CKD stage IV and V, respectively. Hazard ratios for rivaroxaban compared to warfarin were 0.93 (95% CI 0.46-1.90, P = .85) for the risk of ISSE and 0.91 (95% CI 0.65-1.28, P = .60) for major bleeding. CONCLUSIONS: No statistically significant difference in the risk of ISSE or major bleeding was found between rivaroxaban- and warfarin-treated patients. Although further study is needed, rivaroxaban appears to be a reasonable alternative to warfarin for ISSE prevention in the setting of NVAF and stage IV-V CKD.

Rivaroxaban versus warfarin for treatment and prevention of recurrence of venous thromboembolism in African American patients: a retrospective cohort analysis.

BACKGROUND: African Americans are under-represented in trials evaluating oral anticoagulants for the treatment of acute venous thromboembolism (VTE). The aim of this study was to evaluate the effectiveness and safety of rivaroxaban versus warfarin for the treatment of VTE in African Americans. METHODS: We utilized Optum® De-Identified Electronic Health Record data from 11/1/2012-9/30/2018. We included African Americans experiencing an acute VTE during a hospital or emergency department visit, who received rivaroxaban or warfarin as their first oral anticoagulant within 7-days of the acute VTE event and had ≥1 provider visit in the prior 12-months. Differences in baseline characteristics between cohorts were adjusted using inverse probability-of-treatment weighting based on propensity scores (standard differences < 0.10 were achieved for all covariates). Our primary endpoint was the composite of recurrent VTE or major bleeding at 6-months. Three- and 12-month timepoints were also assessed. Secondary endpoints included recurrent VTE and major bleeding as individual endpoints. Cohort risk was compared using Cox regression and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: We identified 2097 rivaroxaban and 2842 warfarin users with incident VTE. At 6-months, no significant differences in the composite endpoint (HR = 0.96, 95%CI = 0.75-1.24), recurrent VTE (HR = 1.02, 95%CI = 0.76-1.36) or major bleeding alone (HR = 0.93, 95%CI = 0.59-1.47) were observed between cohorts. Analysis at 3- and 12-months provided consistent findings for these endpoints. CONCLUSIONS: In African Americans experiencing an acute VTE, no significant difference in the incidence of recurrent VTE or major bleeding was observed between patients receiving rivaroxaban or warfarin.

Comparative effectiveness, safety, and costs of rivaroxaban and warfarin among morbidly obese patients with atrial fibrillation.

BACKGROUND: There are limited data regarding clinical outcomes and healthcare resource utilization of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) who are morbidly obese (body mass index >40 kg/m2 or body weight >120 kg). METHODS: Using data from 2 US healthcare claims databases, we identified patients initiating rivaroxaban or warfarin who had ≥1 medical claim with an AF diagnosis, a diagnostic code for morbid obesity (ICD-9: 278.01, V85.4%; ICD-10: E66.01%, E66.2%, Z68.4%), and a minimum continuous enrollment of 12 months before and 3 months after treatment initiation. Patients were excluded if they had mitral stenosis, a mechanical heart valve procedure, an organ/tissue transplant, or an oral anticoagulant prescription prior to the index date. Rivaroxaban and warfarin patients were 1:1 propensity score matched. Conditional logistic regression was used to compare ischemic stroke/systemic embolism and major bleeding risk. Generalized linear models were used to compare healthcare resource utilization and costs. RESULTS: A total of 3563 matched pairs of morbidly obese AF patients treated with rivaroxaban or warfarin were identified. The majority (81.4%) of patients in the rivaroxaban cohort were receiving the 20 mg dose. The rivaroxaban and warfarin cohorts were well balanced after propensity score matching. The risks of ischemic stroke/systemic embolism and major bleeding were similar for rivaroxaban and warfarin users (stroke/systemic embolism: 1.5% vs 1.7%; odds ratio [OR]: 0.88; 95% confidence interval [CI]: 0.60, 1.28; P = .5028; major bleeding: 2.2% vs 2.7%; OR: 0.80; 95% CI: 0.59, 1.08; P = .1447). Total healthcare costs including medication costs per patient per year (PPPY) were significantly lower with rivaroxaban versus warfarin ($48,552 vs $52,418; P = .0025), which was primarily driven by lower hospitalization rate (50.2% vs 54.1%; P = .0008), shorter length of stay (7.5 vs 9.1 days; P = .0010), and less outpatient service utilization (86 vs 115 visits PPPY; P < .0001). CONCLUSIONS: Morbidly obese AF patients treated with rivaroxaban had comparable risk of ischemic stroke/systemic embolism and major bleeding as those treated with warfarin, but lower healthcare resource utilization and costs.

Evaluation of clinical outcomes among nonvalvular atrial fibrillation patients treated with rivaroxaban or warfarin, stratified by renal function
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BACKGROUND: Renal dysfunction increases the risk of thromboembolic and bleeding events in patients with nonvalvular atrial fibrillation (NVAF). MATERIALS AND METHODS: Adult NVAF patients with ≥ 6 months prior to first warfarin or rivaroxaban dispensing were selected from the IMS Health Real-World Data Adjudicated Claims database (05/2011 - 06/2015) with electronic medical records. Ischemic stroke events, thromboembolic events (venous thromboembolism, myocardial infarction, or ischemic stroke), and major bleeding events were compared between patients by renal function identified by 1) relevant ICD-9-CM diagnosis codes and 2) estimated creatinine clearance (eCrCl). Baseline confounders were adjusted using inverse probability of treatment weights. RESULTS: The diagnosis-based analysis included 39,872 rivaroxaban and 48,637 warfarin users (3,572 and 8,230 with renal dysfunction, respectively). The eCrCl-based analysis included 874 rivaroxaban and 1,069 warfarin users (66 and 208 with eCrCl < 60 mL/min, respectively). In the diagnosis-based analysis, rivaroxaban users with renal dysfunction had a significantly lower stroke rate (HR = 0.55, p = 0.0004) compared to warfarin users; rivaroxaban users with and without renal dysfunction had significantly lower thromboembolic event rates (HR = 0.62, p < 0.0001; and HR = 0.64, p < 0.0001, respectively), and similar major bleeding rates to warfarin users. In the eCrCl-based analysis, rivaroxaban users with eCrCl ≥ 60 mL/min had a significantly lower thromboembolic event rate, but other outcomes were not statistically significant. CONCLUSION: Rivaroxaban-treated NVAF patients with diagnosed renal dysfunction had a significantly lower stroke rate compared to warfarin-treated patients. Regardless of renal dysfunction diagnoses, rivaroxaban users had lower thromboembolic event rates compared to warfarin users, and a similar rate of major bleeding. eCrCl-based analysis was limited by a small sample size.
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Shortened hospital length of stay and lower costs associated with rivaroxaban in patients with pulmonary embolism managed as observation status.

BACKGROUND: Unlike rivaroxaban, treatment of patients with pulmonary embolism (PE) with warfarin requires parenteral bridging and coagulation monitoring that may prolong length-of-stay (LOS) and increase hospital costs. AIMS: The aim of this study was to compare LOS, hospital costs and readmissions in PE patients managed through observation stays treated with rivaroxaban or parenterally bridged warfarin. METHODS: Premier Hospital claims data from November 2012 to March 2015 were used to identify patients with a primary diagnosis code for PE managed through an observation stay and with ≥1 claim for a PE-related diagnostic test on day 0-2. Rivaroxaban users, allowing ≤2 days of prior parenteral therapy, were 1:1 propensity-score matched to patients receiving parenterally bridged warfarin. LOS, the proportion of encounters lasting >2 midnights, total hospital costs of the index visit and risk of readmission for venous thromboembolism (VTE) or major bleeding during the same month or 2 months subsequent to the index event were compared between matched cohorts using multivariable regression. RESULTS: A total of 312 rivaroxaban users were matched to 312 patients receiving parenterally bridged warfarin. Rivaroxaban was associated with an average of 0.27-day shorter LOS, a 52% decreased odds of an encounter lasting >2 midnights and a $403 mean reduction in costs vs parenterally bridged warfarin (P≤.002 for all). The readmission rate for VTE during the same or subsequent 2 months following the index PE was similar between cohorts (P=.75). No patient in either cohort was readmitted for major bleeding. CONCLUSION: Rivaroxaban was associated with shortened LOS and lowered cost vs parenterally bridged warfarin in PE observation stay patients, without increases in the short-term rate of complications or readmission.

Observation management of pulmonary embolism and agreement with claims-based and clinical risk stratification criteria in United States patients: a retrospective analysis.

BACKGROUND: Guidelines suggest observation stays are appropriate for pulmonary embolism (PE) patients at low-risk for early mortality. We sought to assess agreement between United States (US) observation management of PE and claims-based and clinical risk stratification criteria. METHODS: Using US Premier data from 11/2012 to 3/2015, we identified adult observation stay patients with a primary diagnosis of PE, ≥1 PE diagnostic test claim and evidence of PE treatment. The proportion of patients at high-risk was assessed using the In-hospital Mortality for PulmonAry embolism using Claims daTa (IMPACT) equation and high-risk characteristics (age > 80 years, heart failure, chronic lung disease, renal or liver disease, high-risk for bleeding, cancer or need for thrombolysis/embolectomy). RESULTS: We identified 1633 PE patients managed through an observation stay. Despite their observation status, IMPACT classified 46.4% as high-risk for early mortality and 33.3% had ≥1 high-risk characteristic. Co-morbid heart failure, renal or liver disease, high-risk for major bleeding, cancer and hemodynamic instability were low (each <4.5%), but 7.8% were >80 years-of-age and 19.4% had chronic lung disease. CONCLUSION: Many PE patients selected for management in observation stay units appeared to have clinical characteristics suggestive of higher-risk for mortality based upon published claims-based and clinical risk stratification criteria.

Outcomes associated with observation stays versus inpatient admissions for pulmonary embolism.

Changes in reimbursement policies have led to an increased use of observation stays in the United States (US). We sought to compare outcomes among pulmonary embolism (PE) patients managed through observation stays or inpatient admissions.The Premier Perspective Comparative Hospital Database was used to identify patients with a primary International Classification of Diseases, ninth-edition diagnosis of PE (415.1×) from 11/2012-3/2015. Patients were required to have claims for ≥1 diagnostic tests for PE on days 0-2 and evidence of PE treatment. Patients managed through observation stays were 1:1 propensity score matched to those undergoing inpatient admissions. We compared length-of-stay (LOS), hospital costs (2015US$) and rates of hospital-acquired conditions and readmission between the cohorts. A total of 1105 PE observation stays were matched to 1105 inpatient admissions. The baseline characteristics of the cohorts were well-balanced (no standardized differences >10 %). Mean ± standard deviation LOS and hospital costs were 3.6 ± 2.6 days and $5423 ± $5770, respectively. LOS was shorter for observation stays 2.3 ± 1.3 days) vs. inpatient admissions (4.9 ± 3.0 days, p < 0.001). This corresponded to a mean $4390 lower treatment costs for observation stays (p < 0.001). Hospital-acquired conditions were less common among observation stay patients vs. inpatients (p < 0.001); driven predominantly by reductions in bacterial pneumonia and Clostridium difficile infection. Readmission for venous thromboembolism or major bleeding in the same or subsequent 2-months did not differ between the cohorts (p ≥ 0.16 for both).Compared with inpatient admissions, observation stays were associated with reduced LOS, costs and hospital-acquired conditions, without increased risk of readmission.

Assessment of clinical and economic impact of rivaroxaban plus aspirin vs. aspirin alone as a secondary prophylaxis in patients with chronic and symptomatic peripheral arterial disease in the United States.

AIM: The objective in this study was to assess the clinical and economic implications of the inclusion of rivaroxaban as a secondary prophylaxis in patients with chronic or symptomatic peripheral artery disease (PAD) in the United States (US). METHODS: A cost-consequence model was adapted to evaluate the economic impact of rivaroxaban plus aspirin in a hypothetical 1-million-member health plan. The model inputs were taken from multiple sources: efficacy and safety of rivaroxaban + aspirin vs. aspirin alone were abstracted from COMPASS and VOYAGER randomized clinical trials; the prevalence of chronic and symptomatic PAD and incidence rates of clinical events (major adverse cardiac events [MACE], major adverse limb events [MALE], and major bleeding), were abstracted from the analysis of claims data; healthcare costs of clinical events and wholesale acquisition costs for rivaroxaban were abstracted from the literature and Red Book, respectively (2022 USD). One-way sensitivity analyses and subgroup analyses were also conducted. RESULTS: Over one year, with a 5% uptake of rivaroxaban, the model estimated rivaroxaban + aspirin to reduce 21 MACE/MALE events in the PAD patient population. The reduction in these clinical events offsets the increased risk of major bleeding (16 additional events), demonstrating a positive health benefit of the rivaroxaban addition. These benefits led to a $0.27 incremental cost per member per month (PMPM) to a US plan. The major driver of the incremental cost was the cost of rivaroxaban. In a subgroup of patients with the presence of any high-risk factor (heart failure, diabetes, renal insufficiency, or history of vascular disease affecting two or more vascular beds), the incremental PMPM cost was $0.13. CONCLUSIONS: Rivaroxaban + aspirin was found to provide positive net clinical benefit on the annual number of MACE/MALE avoided, with a modest increase in the PMPM cost.

Real-World Impact of Blood Pressure Control in Patients With Apparent Treatment-Resistant or Difficult-to-Control Hypertension and Stages 3 and 4 Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is a common comorbidity in patients with apparent treatment-resistant hypertension (aTRH). We assessed clinical outcomes, healthcare resource utilization events, and costs in patients with aTRH or difficult-to-control hypertension and stage 3-4 CKD with uncontrolled vs. controlled BP. METHODS: This retrospective cohort study used linked IQVIA Ambulatory EMR-US and IQVIA PharMetrics Plus claims databases. Adult patients had claims for ≥3 antihypertensive medication classes within 30 days between 01/01/2015 and 06/30/2021, 2 office BP measures recorded 1-90 days apart, ≥1 claim with ICD-9/10-CM diagnosis codes for CKD 3/4, and ≥1 year of continuous enrollment. Baseline BP was defined as uncontrolled (≥130/80 mm Hg) or controlled (<130/80 mm Hg) BP. Outcomes included risk of major adverse cardiovascular events plus (MACE+; stroke, myocardial infarction, heart failure hospitalization), end-stage renal disease (ESRD), healthcare resource utilization events, and costs during follow-up. RESULTS: Of 3,966 patients with stage 3-4 CKD using ≥3 antihypertensive medications, 2,479 had uncontrolled BP and 1,487 had controlled BP. After adjusting for baseline differences, patients with uncontrolled vs. controlled BP had a higher risk of MACE+ (HR [95% CI]: 1.18 [1.03-1.36]), ESRD (1.85 [1.44-2.39]), inpatient hospitalization (rate ratio [95% CI]: 1.35 [1.28-1.43]), and outpatient visits (1.12 [1.11-1.12]) and incurred higher total medical and pharmacy costs (mean difference [95% CI]: $10,055 [$6,741-$13,646] per patient per year). CONCLUSIONS: Patients with aTRH and stage 3-4 CKD and uncontrolled BP despite treatment with ≥3 antihypertensive classes had an increased risk of MACE+ and ESRD and incurred greater healthcare resource utilization and medical expenditures compared with patients taking ≥3 antihypertensive classes with controlled BP.

Prediction of cardiovascular and renal risk among patients with apparent treatment-resistant hypertension in the United States using machine learning methods.

Apparent treatment-resistant hypertension (aTRH), defined as blood pressure (BP) that remains uncontrolled despite unconfirmed concurrent treatment with three antihypertensives, is associated with an increased risk of developing cardiovascular and renal complications compared with controlled hypertension. We aimed to identify the characteristics of aTRH patients with an elevated risk of major adverse cardiovascular events plus (MACE+; defined as stroke, myocardial infarction, or heart failure hospitalization) and end stage renal disease (ESRD). This retrospective cohort study included aTRH patients (BP ≥140/90 mmHg and taking ≥3 antihypertensives) from the United States-based Optum® de-identified Electronic Health Record dataset and used machine learning models to identify risk factors of MACE+ or ESRD. Patients had claims for ≥3 antihypertensive classes within 30 days between January 1, 2015 and June 30, 2021, and two office BP measures recorded 1-90 days apart within 30 days to 11 months after the index regimen date. Of a total 18 797 070 patients identified with any hypertension, 71 100 patients had aTRH. During the study period (mean 25.5 months), 4944 (7.0%) patients had a MACE+ and 2403 (3.4%) developed ESRD. In total, 22 risk factors were included in the MACE+ model and 16 in the ESRD model, and most were significantly associated with study outcomes. The risk factors with the largest impact on MACE+ risk were congestive heart failure, stages 4 and 5 chronic kidney disease (CKD), age ≥80 years, and living in the Southern region of the United States. The risk factors with the largest impact on ESRD risk, other than pre-existing CKD, were anemia, congestive heart failure, and type 2 diabetes. The overall study cohort had a 5-year predicted MACE+ risk of 13.4%; this risk was increased in those in the top 50% and 25% high-risk groups (21.2% and 29.5%, respectively). The overall study cohort had a predicted 5-year risk of ESRD of 6.8%, which was increased in the top 50% and 25% high-risk groups (10.9% and 17.1%, respectively). We conclude that risk models developed in our study can reliably identify patients with aTRH at risk of MACE+ and ESRD based on information available in electronic health records; such models may be used to identify aTRH patients at high risk of adverse outcomes who may benefit from novel treatment interventions.

Association of uncontrolled blood pressure in apparent treatment-resistant hypertension with increased risk of major adverse cardiovascular events plus.

Patients with apparent treatment-resistant hypertension (aTRH) are at increased risk of end-organ damage and cardiovascular events. Little is known about the effects of blood pressure (BP) control in this population. Using a national claims database integrated with electronic medical records, the authors evaluated the relationships between uncontrolled BP (UBP; ≥130/80 mmHg) or controlled BP (CBP; <130/80 mmHg) and risk of major adverse cardiovascular events plus (MACE+; stroke, myocardial infarction, heart failure requiring hospitalization) and end-stage renal disease (ESRD) in adult patients with aTRH (taking ≥3 antihypertensive medication classes concurrently within 30 days between January 1, 2015 and June 30, 2021). MACE+ components were also evaluated separately. Multivariable regression models were used to adjust for baseline differences in demographic and clinical characteristics, and sensitivity analyses using CBP <140/90 mmHg were conducted. Patients with UBP (n = 22 333) were younger and had fewer comorbidities at baseline than those with CBP (n = 11 427). In the primary analysis, which adjusted for these baseline differences, UBP versus CBP patients were at an 8% increased risk of MACE+ (driven by a 31% increased risk of stroke) and a 53% increased risk of ESRD after 2.7 years of follow-up. Greater MACE+ (22%) and ESRD (98%) risk increases with UBP versus CBP were seen in the sensitivity analysis. These real-world data showed an association between suboptimal BP control in patients with aTRH and higher incidence of MACE+ and ESRD linked with UBP despite the use of multidrug regimens. Thus, there remains a need for improved aTRH management.

Effectiveness and Safety of Rivaroxaban Versus Warfarin among Nonvalvular Atrial Fibrillation Patients with Concomitant Obstructive Sleep Apnea.

Background Obstructive sleep apnea (OSA) is associated with an increased incidence of atrial fibrillation (AF), hypertension, diabetes, heart failure, coronary heart disease, stroke, and death. We sought to evaluate the effectiveness and safety of rivaroxaban versus warfarin in nonvalvular AF (NVAF) patients with concomitant OSA. Methods This was an analysis of electronic health record (EHR) data from November 2010 to December 2021. We included adults with NVAF and OSA at baseline, newly initiated on rivaroxaban or warfarin, and with ≥12 months of prior EHR activity. Patients with valvular disease, alternative indications for oral anticoagulation, or who were pregnant were excluded. The incidence rates of developing stroke or systemic embolism (SSE) and bleeding-related hospitalization were evaluated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using propensity score-overlap weighted proportional hazards regression. Multiple sensitivity and subgroup analyses were performed. Results We included 21,940 rivaroxaban (20.1% at the 15 mg dose) and 38,213 warfarin (time-in-therapeutic range = 47.3 ± 28.3%) patients. Rivaroxaban was found to have similar hazard of SSE compared to warfarin (HR = 0.92, 95% CI = 0.82-1.03). Rivaroxaban was associated with a reduced rate of bleeding-related hospitalizations (HR = 0.85, 95% CI = 0.78-0.92) versus warfarin, as well as reductions in intracranial (HR = 0.76, 95% CI = 0.62-0.94) and extracranial (HR = 0.89, 95%CI = 0.81-0.97) bleeding. Upon sensitivity analysis restricting the population to men with a CHA 2 DS 2 VASc score ≥2 or women with a score ≥3, rivaroxaban was associated with a significant 33% risk reduction in SSE and 43% reduction in the risk of bleeding-related hospitalization. No significant interaction for the SSE or bleeding-related hospitalization outcomes was observed upon subgroup analyses. Conclusion Among patients with NVAF and OSA, rivaroxaban had similar SSE risk versus warfarin but was associated with reductions in any intracranial and extracranial bleeding-related hospitalizations. Rivaroxaban was associated with significant reductions in SSE and bleeding-related hospitalizations when the study population was restricted to patients with a moderate-to-high risk of SSE. These data should provide prescribers with additional confidence in selecting rivaroxaban in NVAF patients who have OSA at the time of anticoagulation initiation.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: After IPTW, 17,881 and 19,274 patients initiated on rivaroxaban and warfarin were included, respectively (mean age: 73 years; 40% female). During 12 months 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 30 day 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). CONCLUSION: Among NVAF patients with diabetes in a real-world US setting, rivaroxaban was associated with lower healthcare costs compared to warfarin.

Comparative outcomes associated with rivaroxaban versus warfarin use in elderly patients with atrial fibrillation or acute venous thromboembolism managed in the United States: a systematic review of observational studies.

BACKGROUND: Advancing age is a risk factor for developing non-valvular atrial fibrillation (NVAF) or acute venous thromboembolism (VTE). We assessed the comparative effectiveness, safety, costs, and healthcare utilization associated with rivaroxaban versus warfarin in patients of advanced age managed in the United States (US). METHODS: We conducted a systematic review of Medline and Embase through April 2023 to identify real-world evidence (RWE) studies of older adults (at least 65+ years of age) with either NVAF or VTE who received either rivaroxaban or warfarin in the US and reported an outcome of stroke or systemic embolism (SSE), ischemic stroke (IS), recurrent VTE, major bleeding, intracranial hemorrhage, costs, or healthcare resource utilization. We classified each outcome of interest per study as "positive" (lower risk), "negative" (higher risk), or "neutral" based upon the summary effect size of rivaroxaban versus warfarin. RESULTS: Twenty-nine RWE studies met inclusion criteria, mostly (83%) in NVAF populations. For SSE with rivaroxaban versus warfarin, 68.8% of studies showed positive effects and 31.2% showed neutral outcome. For major bleeding, 57.7% showed neutral effects, 38.5% showed negative effects, and 3.8% of studies showed positive effects with rivaroxaban versus warfarin. Of the two studies reporting cost data, both were positive, showing lower costs for SSE for rivaroxaban versus warfarin and neutral cost for major bleeding costs. CONCLUSIONS: This systematic review supports findings from subgroup analyses of randomized controlled trials that, compared with warfarin, rivaroxaban is associated with generally neutral or positive effects on thrombosis and a mixed picture on bleeding outcomes in older adults with either NVAF or VTE treated in the United States.

Adherence and persistence to rivaroxaban in non-valvular atrial fibrillation patients receiving 30- or 90-day supply prescription fills.

BACKGROUND: It is unclear whether 90-day supply fills with rivaroxaban result in better adherence and persistence compared to 30-day supply fills. We assessed patients' adherence and persistence to rivaroxaban at 12- and 24-months in nonvalvular atrial fibrillation (NVAF) patients whose rivaroxaban prescriptions were filled every 30- vs. 90-days. METHODS: Using the IBM MarketScan Commercial and Medicare Supplemental data sets, we identified adult NVAF patients with ≥12-months of continuous insurance coverage who filled a prescription in May 2018 and their immediate subsequent prescription for rivaroxaban for the same days' supply. We propensity score-matched 30- and 90-day rivaroxaban interval fill patients and compared the percentage with a proportion of days covered (PDC) ≥80%, mean PDC, and percentage persistent to rivaroxaban therapy over 12- and 24-months of follow-up. RESULTS: Following propensity score matching, 2237 patients were included in the rivaroxaban 30- and 90-day supply fill cohorts. The proportion of patients with a PDC ≥80% was greater in the 90-day vs. 30-day cohort at both 12-months (odds ratio [OR] = 1.75, 95% confidence interval [CI] = 1.54-1.97) and 24-months (OR = 1.78, 95%CI = 1.58-2.00), as were mean PDC values (absolute difference in mean PDC = 9.4%, 95%CI = 8.2-10.7% at 12-months and 11.2%, 95%CI = 9.5-12.9% higher at 24-months, respectively). Persistence to rivaroxaban was not found to significantly differ between the 30- and 90-day supply cohorts at 12- or 24-months (assuming a 30-day permissible gap); however, greater persistence was observed with 90-day fills at both time points when a 14-day gap was utilized (HR = 1.22, 95%CI = 1.10-1.36 at 12-months and HR = 1.12, 95%CI = 1.02-1.22 at 24-months). CONCLUSIONS: Dispensing 90-day supply fills with rivaroxaban appears to increase the proportion of patients achieving acceptable (PDC ≥80%) adherence as well as mean adherence compared to 30-day supply fills. Ninety-day rivaroxaban fills may also result in improved persistence vs. 30-day fills.

Risk factors for recurrent venous thromboembolism: a real-world analysis.

This study was conducted in patients treated for initial venous thromboembolism (VTE) for approximately 6 months to enhance understanding of the risk factors to inform clinical decision-making about long-term anticoagulation therapy. This retrospective cohort study was conducted using a large administrative claims database in the United States. A Cox proportional hazards model was used to examine demographic and clinical characteristics associated with recurrent VTE. A total of 13 831 patients had an index VTE event, and recurrent VTE occurred in 844 (6.1%) of these patients over a median follow-up of 22.8 months. Baseline comorbidities of arrhythmia, congestive heart failure, and chronic kidney disease were significantly associated with recurrent VTE. During the period of anticoagulation treatment after the index VTE, use of antidepressants was associated with an increased risk of recurrent VTE, whereas use of antibiotics and major surgery were associated with a decreased risk. In the 6 months prior to index VTE, anti-inflammatory agents and major surgery were associated with a decreased risk of recurrent VTE. The type of index VTE was also significantly associated with recurrent VTE, with an increased risk observed in patients with pulmonary embolism (PE) alone or PE with deep vein thrombosis (DVT) versus DVT alone. This real-world analysis identified baseline comorbidities, medications, and index VTE type to be factors predictive of recurrent VTE among patients treated for index VTE for approximately 6 months. Consideration of these factors may assist in the identification of patients who may benefit from extended anticoagulant therapy.

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

BACKGROUND: Current 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. METHODS: This 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). RESULTS: A 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. CONCLUSIONS: In 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.