Eligibility for Low-Dose Rivaroxaban Based on the COMPASS Trial: Insights from the Veterans Affairs Healthcare System.

INTRODUCTION: Low-dose rivaroxaban reduced major adverse cardiac and limb events among patients with stable atherosclerotic vascular disease (ASCVD) in the COMPASS trial. The objective of our study was to evaluate the eligibility and budgetary impact of the COMPASS trial in a real-world population. METHODS: The VA administrative and clinical databases were utilized to conduct a cross-sectional study to identify patients eligible for low-dose rivaroxaban receiving care at all 141 facilities between October 1, 2014 and September 30, 2015. Proportion of patients with stable ASCVD eligible for low-dose rivaroxaban and prevalence of multiple risk enrichment criteria among eligible patients. Pharmaceutical budgetary impact using VA pharmacy pricing. Chi-squared and Student's t tests were used to compare patients eligible versus ineligible patients. RESULTS: From an initial cohort of 1,248,214 patients with ASCVD, 488,495 patients (39.1%) met trial eligibility criteria. Eligible patients were older (74.2 vs 64.5 years) with higher proportion of hypertension (84.1% vs 82.1%) and diabetes (46.2% vs 32.9) compared with ineligible patients (p < 0.001 for all comparisons). A median of 38.7% (IQR 4.6%) of total ASCVD patients per facility were rivaroxaban eligible. Estimated annual VA pharmacy budgetary impact would range from $0.47 billion to $1.88 billion for 25% to 100% treatment penetration. Annual facility level pharmaceutical budgetary impact would be a median of $12.3 million (IQR $8.0-$16.3 million) for treatment of all eligible patients. Among eligible patients, age greater than 65 years was the most common risk enrichment factor (86.9%). Prevalence of eligible patients with multiple enrichment factors varied from 34.2% (one factor) to 6.2% (four or more). CONCLUSION: Over one third of patients with stable ASCVD may qualify for low-dose rivaroxaban within the VA. Additional studies are needed to understand eligibility in other populations and a formal cost-effectiveness analysis is warranted.

Cost-effectiveness analysis of rivaroxaban plus aspirin versus aspirin alone in secondary prevention among patients with chronic cardiovascular diseases.

PURPOSE: This study aimed to investigate the cost-effectiveness of low-dose rivaroxaban plus aspirin versus aspirin alone for patients with stable cardiovascular diseases in the Taiwan setting. METHODS: We constructed a Markov model to project the lifetime direct medical costs and quality-adjusted life-years of both therapies. Transitional probabilities were derived from the COMPASS trial, and the costs and utilities were obtained from the Taiwan National Health Insurance Database and published studies. One-way, scenario, subgroup, and probabilistic sensitivity analyses were performed to assess the uncertainty. Incremental cost-effectiveness ratio was presented as the outcome. The threshold of willingness-to-pay was set at US$76,368 (3 times the gross domestic product per capita of Taiwan). All analyses were operated by TreeAge 2019 and Microsoft Excel. RESULTS: The incremental cost-effectiveness ratios of rivaroxaban plus aspirin versus aspirin alone in the patients with stable cardiovascular diseases, coronary artery diseases, and peripheral artery diseases were US$83,459, US$69,852 and -US$13,823 per quality-adjusted life-year gained, respectively. The probabilistic sensitivity analyses showed that the probabilities of cost-effectiveness for the regimen with rivaroxaban among those with cardiovascular diseases and coronary artery diseases were 44.1% and 65.3% at US$76,368. CONCLUSION: Low-dose rivaroxaban plus aspirin is less likely to be a cost-effective alternative to aspirin in secondary prevention for the patients with stable cardiovascular diseases; however, among these patients, the regimen may have pharmacoeconomic incentives for the group merely having chronic coronary artery diseases from the Taiwan national payer's perspective. The pharmacoeconomic incentives are influenced by the drug price, event treatment fees, and willingness-to-pay threshold.

Cost-effectiveness of rivaroxaban versus warfarin in non-valvular atrial fibrillation patients with chronic kidney disease in China.

WHAT IS KNOWN AND OBJECTIVE: In non-valvular atrial fibrillation (NVAF) patients with chronic kidney disease (CKD), rivaroxaban was not inferior to warfarin in preventing stroke and systemic embolism. However, a comparative evaluation of the cost-effectiveness of rivaroxaban and warfarin therapies for NVAF patients at different renal function levels has not yet been reported, and this study aimed to estimate the cost-effectiveness of rivaroxaban compared with warfarin in Chinese NVAF patients with CKD. METHODS: A Markov model was constructed to estimate quality-adjusted life years (QALYs) and lifetime costs associated with the use of rivaroxaban relative to warfarin in patients with NVAF at different estimated glomerular filtration rate (eGFR) levels as follows: 30 to <50, 50 to <80 and ≥80 mL/min. Input parameters were sourced from the clinical literature. Probabilistic sensitivity analyses were performed to assess model uncertainty. RESULTS AND DISCUSSION: The incrementalQALYs with rivaroxaban was slightly increased by approximately 0.3 QALY as compared with that with warfarin in all the subgroups, resulting in an ICER of $9,736/QALY (eGFR, 30 to <50 mL/min), $9,758/QALY (50 to <80 mL/min) and $9,969/QALY (≥80 mL/min). The probabilistic sensitivity analysis suggested a chance of >80% that the ICER would be lower than the willingness-to-pay threshold of three times the GDP of China in 2019 in all the subgroups. Results were consistent even under the assumption of anticoagulant discontinuation after major bleeding events. The model was most sensitive to event-free-related utility and survival rates. WHAT IS NEW AND CONCLUSION: The existing evidence supports the cost-effectiveness of rivaroxaban therapy as an alternative anticoagulant to warfarin for patients with NVAF at different renal function levels.

Cost-Effectiveness of Coronary and Peripheral Artery Disease Antithrombotic Treatments in Finland.

INTRODUCTION: Currently, 15-20% of individuals with coronary artery disease (chronic coronary syndrome [CCS]) or peripheral artery disease (PAD) receiving routine treatment experience cardiovascular events (CVEs) within 3-4 years. Using PICOSTEPS (Patients-Intervention-Comparators-Outcomes-Setting-Time-Effects-Perspective-Sensitivity analysis) reporting, we evaluated the cost-effectiveness of recently approved rivaroxaban 2.5 mg twice daily in combination with acetylsalicylic acid 100 mg daily (RIV + ASA) for the prevention of CVEs among Finns with CCS or symptomatic PAD. METHODS: Myocardial infarction, ischemic stroke, intracranial hemorrhage, acute limb ischemia, amputations, major extracranial bleeding, venous thromboembolism, and cardiovascular deaths were modeled in a Markov model examining a cohort of patients with CCS or symptomatic PAD. Relative effects of the intervention (RIV + ASA) and comparator (ASA) were based on the COMPASS trial. The primary outcome was 3%/year discounted incremental cost-effectiveness ratio (ICER), defined as cost (2019 euros) per quality-adjusted life year (QALY) gained in the Finnish setting over a lifetime horizon. In addition to nonfatal and fatal CVEs, the effects factored Finnish non-CVE mortality, quality of life, and direct costs from a public payer perspective. Disaggregated costs and QALYs, costs per life year gained (LYG), and ischemic strokes avoided, net monetary benefit (NMB), expected value of perfect information (EVPI), economic value-added (EVA), cost-effectiveness table, and acceptability frontier were examined. Probabilistic and deterministic sensitivity analyses were conducted. RESULTS: In the deterministic comparison with ASA over a lifetime horizon, RIV + ASA resulted in a benefit of 0.404 QALYs and 0.474 LYGs for an additional cost of €3241, resulting in an ICER of €8031/QALY. The probabilistic ICER was €4313/QALY (EVPI €1829/patient). RIV + ASA had positive NMB (€8791/patient), low EVPI (€88/patient), high EVA (€8703/patient), and 91% probability of cost-effectiveness using the willingness-to-pay of €25,254/QALY. The primary result was conservative and robust for RIV + ASA. CONCLUSION: RIV + ASA was a cost-effective treatment alternative compared with ASA in patients with CCS or symptomatic PAD in Finland.

Finland lacks published evidence on the cost-effectiveness of approved interventions for the prevention of cardiovascular events among individuals with chronic coronary syndrome (stable coronary artery disease) or symptomatic peripheral artery disease at risk of cardiovascular complications. Rivaroxaban 2.5 mg twice daily plus acetylsalicylic acid 100 mg once daily is indicated and reimbursed in Finland for the prevention of cardiovascular events for patients with stable coronary artery disease or symptomatic peripheral artery disease. We assessed the effectiveness and costs of treatment with rivaroxaban plus acetylsalicylic acid in comparison with treatment with acetylsalicylic acid. That is, we examined whether rivaroxaban is cost-effective when prescribed in combination with acetylsalicylic acid.Cardiovascular events with their associated costs and impact on quality of life were modeled over the lifetime of patients. The main effectiveness outcome was quality-adjusted life years (modeled survival multiplied by the expected quality of life), and costs included those relevant to the Finnish public payer in 2019. Extensive sensitivity analyses were carried out to evaluate the impacts of different model inputs and rationale.Rivaroxaban plus acetylsalicylic acid had high probability of being cost-effective, compared with acetylsalicylic acid. By valuing quality-of-life benefit with a plausible willingness-to-pay, net cost savings of €8791 per patient could be gained or economic value added by €8703 per patient if rivaroxaban was used.

Health economic evaluation of rivaroxaban in the treatment of patients with chronic coronary artery disease or peripheral artery disease.

AIMS: In the COMPASS trial, rivaroxaban 2.5 mg twice daily (bid) plus acetylsalicylic acid (ASA) 100 mg once daily (od) performed better than ASA 100 mg od alone in reducing the rate of cardiovascular disease, stroke, or myocardial infarction (MI) in patients with coronary artery disease (CAD) and peripheral artery disease (PAD). A Markov model was developed to assess the cost-effectiveness of rivaroxaban plus ASA vs. ASA alone over a lifetime horizon, from the UK National Health System perspective. METHODS AND RESULTS: The base case analysis assumed that patients entered the model in the event-free health state, with the possibility to experience ≤2 events, transitioning every three-month cycle, through acute and post-acute health states of MI, ischaemic stroke (IS), or intracranial haemorrhage (ICH), and death. Costs, quality-adjusted life-years (QALYs), life years-all discounted at 3.5%-and incremental cost-effectiveness ratios (ICERs) were calculated. Deterministic and probabilistic sensitivity analyses were conducted, as well as scenario analyses. In the model, patients on rivaroxaban plus ASA lived for an average of 14.0 years with no IS/MI/ICH, and gained 9.7 QALYs at a cost of £13 947, while those receiving ASA alone lived for an average of 12.7 years and gained 9.3 QALYs at a cost of £8126. The ICER was £16 360 per QALY. This treatment was cost-effective in 98% of 5000 iterations at a willingness-to-pay threshold of £30 000 per QALY. CONCLUSION: This Markov model suggests that rivaroxaban 2.5 mg bid plus ASA is a cost-effective alternative to ASA alone in patients with chronic CAD or PAD.

Rivaroxaban versus warfarin treatment among morbidly obese patients with venous thromboembolism: Comparative effectiveness, safety, and costs.

INTRODUCTION: Limited data exist on direct-acting oral anticoagulants in morbidly obese patients with venous thromboembolism (VTE). We compared clinical and health/economic outcomes with rivaroxaban versus warfarin for VTE treatment in morbidly obese patients. MATERIALS AND METHODS: This retrospective 1:1 propensity score matched cohort study analyzed data from 2 US claims databases. VTE patients initiating rivaroxaban or warfarin were identified who had diagnosis codes for morbid obesity (ICD-9:278.01,V85.4; ICD-10:E66.01,E66.2,Z68.4) 12 months pre- or 3 months post-initiation and followed ≥3 months. Intent-to-treat (ITT) and on-treatment (OT) analyses were conducted using conditional logistic regression and generalized linear models to compare recurrent VTE and major bleeding risks, healthcare resource utilization (HRU), and per patient per year (PPPY) costs. RESULTS: In total, 2890 matched pairs of morbidly obese VTE patients initiating rivaroxaban or warfarin were identified. Risks of recurrent VTE (ITT: OR: 0.99; 95% CI: 0.85-1.14) and major bleeding (OT: OR: 0.75; 95% CI: 0.47-1.19) were similar for cohorts. Anti-Factor Xa laboratory measurement was performed on <1% of rivaroxaban cohort. Hospitalizations (OR: 0.86; 95% CI: 0.77-0.96) and outpatient visits (OR: 0.23; 95% CI: 0.10-0.56), were lower with rivaroxaban versus warfarin (ITT analysis). Average total medical costs PPPY were $2829 lower with rivaroxaban versus warfarin ($34,824 vs $37,653), mainly driven by hospitalization costs. Total healthcare costs (including pharmacy) were similar ($43,034 vs $44,565). CONCLUSIONS: Morbidly obese VTE patients receiving rivaroxaban had similar risks of recurrent VTE and major bleeding versus warfarin. Rivaroxaban treatment yielded significantly less HRU and total medical costs, with similar total healthcare costs between groups.

Cost effectiveness analysis of direct oral anticoagulant (DOAC) versus dalteparin for the treatment of cancer associated thrombosis (CAT) in the United States.

INTRODUCTION: While trials have demonstrated non-inferiority of direct oral anticoagulant drugs (DOAC) to low-molecular-weight heparins (LMWH) for the treatment of cancer associated thrombosis (CAT), it is unclear if the newer intervention is cost-effective. METHODS: We performed a cost-utility analysis using a Markov state-transition model over a time horizon of 60 months in a hypothetical cohort of 65-year-old patients with active malignancy and first acute symptomatic CAT who were eligible to receive either rivaroxaban/edoxaban or dalteparin. We obtained transition probability, relative risk, cost, and utility inputs from the literature. We estimated the differential impact on costs and quality-adjusted life years (QALYs) per patient and performed one-way and probabilistic sensitivity analyses to test the robustness of results. RESULTS: Using the base-case analysis over 60 months, DOAC versus dalteparin was associated with an incremental cost reduction of $24,129 with an incremental QALY reduction of 0.04. In the one-way sensitivity analysis, the cost of dalteparin contributed the most to the incremental cost difference; relative risk of death related to underlying cancer contributed the most of the incremental QALY difference. The probabilistic sensitivity analysis confirmed the base-case analysis, with a large reduction in cost but small reduction in QALYs. CONCLUSION: Rivaroxaban or edoxaban as compared to dalteparin is cost saving from a payer's perspective for the treatment of CAT. Professional organizations and healthcare systems may want to consider this analysis in future practice recommendations.

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.

Health Economic Analysis of Rivaroxaban and Warfarin for Venous Thromboembolism Management in Chinese Patients.

PURPOSE: Rivaroxaban, a direct oral anticoagulant, has demonstrated non-inferiority to warfarin for venous thromboembolism (VTE) treatment in clinical trials. This study aimed to analyze the direct medical costs for VTE management with rivaroxaban versus warfarin in Hong Kong Chinese patients. METHODS: In this retrospective observational study, VTE patients admitted to the Princess Margaret Hospital from March 2012 to February 2017 who were initiated and discharged with either rivaroxaban or warfarin were included. Patient demographic and clinical data, and healthcare resource utilization for VTE management were collected for the VTE index admission and 1-year post-discharge period. RESULTS: A total of 181 patients (90 in the rivaroxaban group; 91 in the warfarin group) were included. The mean (± SD) length of stay (LOS) was 4.8 ± 2.7 days and 8.0 ± 3.0 days in the rivaroxaban and warfarin groups, respectively (p > 0.001). The total cost for VTE index admission in the rivaroxaban group was significantly lower than that of the warfarin group (USD 5473 ± 1914 versus USD 3457 ± 1796; p < 0.001) (USD 1 = HKD 7.8). Recurrent VTE and bleeding rates in 1-year post-discharge period were not significantly different between the two groups. The direct total cost of the rivaroxaban group (USD 1271 ± 767) was significantly lower than that of the warfarin group (USD 1739 ± 1045) in 1-year post-discharge period (p < 0.001). CONCLUSIONS: Total direct cost and LOS for VTE admission and total cost in 1-year post-discharge period were significantly lower in patients initiated and discharged with rivaroxaban than those of warfarin.

Cost-Effectiveness Analysis of Direct-Acting Oral Anticoagulants for Stroke Prevention in Thai Patients with Non-Valvular Atrial Fibrillation and a High Risk of Bleeding.

OBJECTIVE: The objective of this study was to assess the cost effectiveness of direct-acting oral anticoagulants for stroke prevention in Thai patients with non-valvular atrial fibrillation and a HAS-BLED score of 3. METHODS: Total costs (US$) in 2017 and quality-adjusted life-years were estimated over 20 years using a Markov model. A base-case analysis was conducted under a societal perspective, which included direct healthcare, non-healthcare and indirect costs in Thailand. Clinical events for warfarin and utilities were obtained from Thai patients whenever possible. The efficacy of direct-acting oral anticoagulants was derived from trial-based East Asian subgroups and adjusted for time in the target international normalized ratio range of warfarin. RESULTS: In the base case, use of apixaban instead of warfarin incurred an additional cost of US$20,763 per quality-adjusted life-year gained. Substituting apixaban with rivaroxaban and rivaroxaban with high-dose edoxaban would incur an additional cost per quality-adjusted life-year by US$507 and US$434, respectively. Compared with warfarin, high-dose edoxaban had the lowest incremental cost-effectiveness ratio of US$9704/quality-adjusted life-year, followed by high-dose dabigatran (incremental cost-effectiveness ratio US$11,155/quality-adjusted life-year). The incremental cost-effectiveness ratios based on a payer perspective were similar. The incremental cost-effectiveness ratio was below Thailand's cost-effectiveness threshold when high-dose dabigatran and edoxaban prices were reduced by 50%. Changes in key parameters had a minimal impact on incremental cost-effectiveness ratios. CONCLUSIONS: For both societal and payer perspectives, high-dose edoxaban with a price below the country cost-effectiveness threshold should be the first anticoagulant option for Thai patients with non-valvular atrial fibrillation and a high risk of bleeding.

Cost-effectiveness of rivaroxaban versus warfarin for treatment of nonvalvular atrial fibrillation in patients with worsening renal function.

BACKGROUND: Nonvalvular atrial fibrillation (NVAF) is highly prevalent and increases the risks of cardiovascular events. In a recent subgroup analysis, treatment response was shown to vary for patients exhibiting worsening renal function (WRF) on-treatment. It is important to understand the cost-effectiveness of novel oral anticoagulant (NOAC) use in this population. METHODS: A cost-effectiveness analysis (CEA) was conducted using a Markov model to determine whether NOAC rivaroxaban treatment is cost-effective relative to warfarin in NVAF patients with on-treatment WRF. Input parameters were sourced from clinical literature including a multicenter clinical trial and subgroup analysis. We studied elderly US male patients at increased risk for stroke (CHADS2 score ≥ 2) undergoing treatment for NVAF and exhibiting WRF. Main outcome measures included total healthcare costs in 2017 US dollars (societal perspective), total quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and incremental net monetary benefits (INMB) per-patient. RESULTS: The remaining lifetime use of rivaroxaban is associated with 5.69 QALYs at a cost of $66,075 per patient, while warfarin produced 5.22 QALYs with costs of $78,504 per patient. At a willingness-to-pay (WTP) of $150,000 per QALY, incremental net monetary benefits (INMB) per patient are $83,590. In our population, treatment with warfarin was dominated by rivaroxaban in 99.4% of 10,000 simulations. CONCLUSIONS: Rivaroxaban is likely a dominant treatment over warfarin in elderly US male NVAF patients exhibiting WRF, providing increased QALYs at a decreased overall cost. Application of these findings may require healthcare providers to predict which patients are likely to exhibit WRF.

Cost-Utility Analysis of Apixaban versus Warfarin in Atrial Fibrillation Patients with Chronic Kidney Disease.

BACKGROUND: Warfarin use for stroke prevention in atrial fibrillation (AF) patients with chronic kidney disease is debated. Apixaban was shown to be safer than warfarin, with superior reduction in the risk of stroke, systemic embolism, mortality, and major bleeding irrespective of kidney function. OBJECTIVES: To evaluate the cost-utility of apixaban compared with warfarin in AF patients at different levels of kidney function. METHODS: A Markov model was used to estimate the cost effectiveness of apixaban compared with warfarin in AF patients at three levels of kidney function: estimated glomerular filtration rate (eGFR) of more than 80 ml/min, 50 to 80 ml/min, and 50 ml/min or less. Event rates and associated utilities were obtained from previous literature. The model adopted the US health care system perspective, with hospitalization costs extracted from the Healthcare and Utilization Project. Treatment costs were obtained from official price lists. Univariate and probabilistic sensitivity analyses were performed to evaluate the robustness of results. RESULTS: Apixaban was a dominant treatment strategy compared with warfarin in AF patients with eGFR levels of 50 ml/min or less and 50 to 80 ml/min. In patients with an eGFR of more than 80 ml/min, apixaban was cost-effective compared with warfarin, costing $6307 per quality-adjusted life-year gained. Results were consistent assuming anticoagulant discontinuation after major bleeding events. Compared with dabigatran and rivaroxaban, apixaban was the only cost-effective anticoagulant strategy relative to warfarin in both mild and moderate renal impairment settings. CONCLUSIONS: Apixaban is a favorably cost-effective alternative to warfarin in AF patients with normal kidney function and potentially cost-saving in those with renal impairment.

Rivaroxaban vs. warfarin on extended deep venous thromboembolism treatment: A cost analysis.

Background Standard treatment for deep venous thromboembolism involves parenteral anticoagulation overlapping with a vitamin K antagonist, an approach that is effective but associated with limitations including the need for frequent coagulation monitoring. The direct oral anticoagulant rivaroxaban is similarly effective to standard therapy as a single-drug treatment for venous thromboembolism and does not require routine coagulation monitoring. The aim of this analysis was to project the long-term costs and outcomes for rivaroxaban compared to standard of care (tinzaparin/warfarin). Methods A total of 184 patients who were under anticoagulant therapy with warfarin or rivaroxaban for extended deep venous thromboembolism were retrospectively evaluated; 59 received rivaroxaban and 125 received warfarin therapy. Assessments were made on age, gender, place of residence, the duration of anticoagulation, mean international normalized ratio value, the effective rate of international normalized ratio (time in the therapeutic range), bleeding-related complication rate, duration of hospitalization due to complications, the number of annual outpatient department admission, cost for drug, cost for hospitalization, cost for outpatient department admission and international normalized ratio measurements. Results The annual outpatient cost is higher in warfarin group (147.09 ± 78 vs. 62.32 ± 19.79 USD p < 0.001). But annual drug cost is higher in rivaroxaban group (362.6 vs. 71.55 ± 31.01 USD p < 0.001). Overall cost of rivaroxaban group is higher than warfarin group (476.25 ± 36.78 vs. 364.82 ± 174.44 USD). Warfarin is not cost-effective when non-drug costs (342.5 ± 174.44 vs. 113.65 ± 36.77) and hospital costs (173.85 ± 122.73 vs. 64.9 ± 23.55 USD) were analyzed. Conclusion This analysis suggests that rivaroxaban has lower costs than warfarin in terms of outpatient department admission and hospital costs due to complications; however, warfarin was more economic when all cost parameters were considered. Time in the therapeutic range was found as 56% for warfarin that should be taken into account while analyzing costs and benefits.

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

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

Rivaroxaban versus Heparin Bridging to Warfarin Therapy: Impact on Hospital Length of Stay and Treatment Costs for Low-Risk Patients with Pulmonary Embolism.

STUDY OBJECTIVE: To compare hospital length of stay (LOS) and hospital treatment costs in low-risk patients with pulmonary embolism (PE) anticoagulated with rivaroxaban or heparin bridging to warfarin therapy. DESIGN: Retrospective review of electronic health records and hospital billing records. SETTING: Large, teaching hospital in the northeastern United States. PATIENTS: One hundred ninety adults with objectively confirmed acute PE presenting to the emergency department between November 1, 2012, and May, 12, 2015, who were classified as low risk of early mortality and received anticoagulation with either rivaroxaban or heparin (i.e., unfractionated heparin or low-molecular-weight heparin) bridging to warfarin therapy were included in the analysis. Patients were identified as low risk by at least one of the following prediction rules: simplified Pulmonary Embolism Severity Index (sPESI; 115 patients), Hestia criteria (87 patients), or In-hospital Mortality for Pulmonary Embolism using Claims Data (IMPACT; 108 patients); these were not mutually exclusive, as patients could be classified as low risk by more than one risk stratification tool. MEASUREMENTS AND MAIN RESULTS: We divided low-risk patients identified by each prediction rule into two cohorts: those receiving rivaroxaban (allowing ≤ 2 days of prior heparin use) or heparin bridging to warfarin therapy. The primary end points for this study were LOS (number of days from the patient's arrival at our institution until discharge) and total hospital treatment costs (our institution's actual costs to provide treatment) for the index PE hospital encounter. Using multivariable generalized linear model regression (gamma-distributed error and log-link), we estimated differences in LOS and hospital costs (in 2015 U.S. dollars) between the two cohorts after covariate adjustment. Rivaroxaban was associated with significantly shorter adjusted LOS (range -2.1 to -4.3 days) and significantly lower index hospital costs (range -$3835 to -$7094) versus heparin bridging to warfarin, regardless of the prediction rule used to identify low-risk patients. CONCLUSION: Among low-risk PE patients identified by using sPESI, Hestia or IMPACT, rivaroxaban was associated with significantly shorter LOS and lower hospital treatment costs versus heparin bridging to warfarin.

A Direct Oral Anticoagulant as a Cost Effective Alternative to Warfarin for Treatment of Provoked Venous Thrombosis.

In Ireland, Warfarin is the primary anticoagulant prescribed in the secondary prevention of provoked DVT. We completed a comprehensive cost analysis of a trial group of 24 patients treated with Rivaroxaban (between November 2013 and December 2014), versus a control group treated with Warfarin (between January 2008 and November 2013). The groups were matched for gender (3/7 M/F ratio), DVT type (5 proximal, 19 distal DVTs), provoking factor (20 traumatic, 4 atraumatc), and age. We calculated the cost for each group based on drug administration and clinic costs (labour, sample analysis, and additional costs). Warfarin patients attended clinic 14.58 times; Rivaroxaban patients attended 2.92 times. Overall, the cost per patient on Rivaroxaban is €273.30 versus €260.68 with warfarin. This excludes patient costs which would further increase cost of Warfarin therapy.

Patient-reported treatment satisfaction and budget impact with rivaroxaban vs. standard therapy in elective cardioversion of atrial fibrillation: a post hoc analysis of the X-VeRT trial.

AIMS: We compared patient-reported treatment satisfaction and the economic impact of anticoagulation therapy with rivaroxaban vs. vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation undergoing elective cardioversion procedures. METHODS AND RESULTS: The current study is a post hoc analysis of the prospective, multicentre X-VeRT (EXplore the efficacy and safety of once-daily oral riVaroxaban for the prevention of caRdiovascular events in subjects with non-valvular aTrial fibrillation scheduled for cardioversion) trial. Patient-reported treatment satisfaction with anticoagulation therapy was assessed using the Treatment Satisfaction Questionnaire for Medication version II in seven countries (US, UK, Canada, Germany, France, Italy, and the Netherlands). An economic model was also developed to estimate the impact of postponed cardioversions for two countries (UK and Italy). This model estimated the total costs of cardioversion, taking into consideration the costs for drug therapy (including extended treatment duration due to cardioversion postponement), international normalized ratio monitoring of VKAs, the cardioversion procedure, and rescheduling the procedure. These costs were linked to the respective X-VeRT study data to estimate the total costs. Patients receiving rivaroxaban in the delayed cardioversion group had significantly higher scores for Convenience, Effectiveness, and Global satisfaction (81.74 vs. 65.78; 39.41 vs. 32.95; and 82.07 vs. 66.74, respectively; P < 0.0001). Based on the total patient population included in the treatment satisfaction substudy (n = 632) in the delayed cardioversion group in X-VeRT, the use of rivaroxaban was estimated to result in a saving of £421 and €360 per patient in UK and Italian settings, respectively. CONCLUSION: The use of rivaroxaban in the setting of cardioversion resulted in greater patient satisfaction and cost savings, compared with that of VKA.

Edoxaban: a review in nonvalvular atrial fibrillation.

The factor Xa inhibitor edoxaban (Lixiana(®)) is a new direct oral anticoagulant recently approved in the EU for the prevention of stroke and systemic embolic events (SEE) in patients with nonvalvular atrial fibrillation and one or more risk factors. In the large, randomized, double-blind, double-dummy, ENGAGE AF-TIMI 48 trial, oral edoxaban dosages of 30 and 60 mg once daily for a median treatment duration of 907 days in patients with moderate-to-high-risk nonvalvular atrial fibrillation were noninferior to warfarin for the incidence of first stroke or SEE. Both high-dose and low-dose edoxaban were associated with significantly lower rates than warfarin of major bleeding, including intracranial haemorrhage, and death from cardiovascular causes. Edoxaban has a rapid onset of action, a short half-life, few drug interactions and offers the convenience of oral, once-daily, fixed-dose administration, without the need for coagulation monitoring and without regard to food. Therefore, edoxaban is an effective and well tolerated therapeutic option in patients with nonvalvular atrial fibrillation.