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Objectives: To demonstrate how health technology assessment methods can be used to support Medicare's price negotiations for apixaban and rivaroxaban., Methods: Following the statutory outline of evidence that will be considered by Medicare, we conducted a systematic literature review, network meta-analyses, and decision analyses to evaluate the health outcomes and costs associated with apixaban and rivaroxaban compared with warfarin and dabigatran for patients with nonvalvular atrial fibrillation. Our methods inform discussions about the therapeutic impact of apixaban and rivaroxaban and suggest price premiums above their therapeutic alternatives over a range of cost-effectiveness thresholds., Results: Network meta-analyses found apixaban resulted in a lower risk of major bleeding compared with warfarin and dabigatran and a lower risk of stroke/systemic embolism compared with warfarin but not compared with dabigatran. Rivaroxaban resulted in a lower risk of stroke/systemic embolism versus warfarin but not dabigatran, and there was no difference in major bleeding. Decision-analytic modeling of apixaban suggested annual price premiums up to $4350 above the price of warfarin and up to $530 above the price for dabigatran at cost-effectiveness thresholds up to $200 000 per equal value of life-years gained. Analyses of rivaroxaban showed an annual price premium of up to $3920 above warfarin and no premium above that paid for dabigatran., Conclusions: Although health technology assessment is typically performed near the time of regulatory approval, with modifications, we produced comparative clinical and relative cost-effectiveness findings to help guide negotiations on a "fair" price for drugs on the market for over a decade., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Prior approval for reimbursement is a policy of cost containment while ensuring oversight and governance of medicines. It has been employed in Ireland to address financial challenges due to the shift from warfarin to direct oral anticoagulants (DOACs). Studies assessing the effectiveness of this policy are limited. Thus, we aimed to examine the effectiveness of prior approval for reimbursement of DOACs (apixaban, rivaroxaban) as a cost containment policy in Ireland., Methods: The Irish Health Service Executive-Primary Care Reimbursement Service database was used in this cross-sectional study. We examined the prescribing frequencies and associated costs of the oral anticoagulants; [(OACs) apixaban, rivaroxaban and warfarin] listed in the top 100 most frequently prescribed drugs, between 2018 and 2021. Time series negative binomial regression was used to assess the impact of removing the approval requirement of apixaban in September 2019 followed by the other DOACs in November 2020., Results: The prescribing frequency of OACs increased by almost 20% from 2018 to 2021. This study showed there were significant differences in the proportion of OACs prescribed among the Community Drug Schemes. A statistically significant decreased use of apixaban (< 1%, p < 0.05) occurred when prior approval was removed for all DOACs., Conclusions: The removal of prior approval for reimbursement of DOACs in Ireland had a minimal impact on the prescribing frequency trends of the OACs. Future use of these potentially useful policies by healthcare systems requires careful consideration of drug type, approval criteria and length of time the policy remains in place to minimise any negative effects associated with their use., (© 2024 The Author(s). Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Objective: Patients undergoing gynecologic cancer surgery at our centre are recommended up to 28 days of enoxaparin for extended post-operative thromboprophylaxis (EP). Baseline survey revealed 92% patient adherence, but highlighted negative effects on patient experience due to the injectable route of administration. We aimed to improve patient experience by reducing pain and bruising by 50%, increasing adherence by 5%, and reducing out-of-pocket cost after introducing apixaban as an oral alternative for EP., Methods: In this interrupted time series quality improvement study, gynecologic cancer patients were offered a choice between apixaban (2.5 mg orally twice daily) or enoxaparin (40 mg subcutaneously once daily) at time of discharge. A multidisciplinary team informed project design, implementation, and evaluation. Process interventions included standardized orders, patient and care team education programs. Telephone survey at 1 and 6 weeks and chart audit informed outcome, process, and balancing measures., Results: From August to October 2022, 127 consecutive patients were included. Apixaban was chosen by 84%. Survey response rate was 74%. Patients who chose apixaban reported significantly reduced pain, bruising, increased confidence with administration, and less negative impact of the medication (p < 0.0001 for all). Adherence was unchanged (92%). The proportion of patients paying less than $125 (apixaban cost threshold) increased from 45% to 91%. There was no difference in bleeding and no VTE events., Conclusions: Introduction of apixaban for EP was associated with significant improvement in patient-reported quality measures and reduced financial toxicity with no effect on adherence or balancing measures. Apixaban is the preferred anticoagulant for EP at our centre., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest. AL reports consulting fees from Bayer, Bristol-Myers Squibb, Janssen and Pfizer unrelated to this project., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: This study evaluates the cost-effectiveness of Apixaban and Rivaroxaban, compared to Warfarin, for stroke prevention in patients with non-valvular atrial fibrillation in Iran., Method: A Markov model with a 30-year time horizon was employed to simulate and assess different treatment strategies' cost-effectiveness. The study population comprised Iranian adults with NVAF, identified through specialist consultations, hospital visits, and archival record reviews. Direct medical costs, direct nonmedical, and indirect costs were included. Quality-adjusted life years (QALY) were assessed using an EQ-5D questionnaire. This study utilized a cost-effectiveness threshold of $11 134 per QALY., Results: Apixaban demonstrated superior cost-effectiveness compared to Rivaroxaban and Warfarin. Over 30 years, total costs were lower in the Apixaban and Rivaroxaban groups compared to the Warfarin group ($126.18 and $109.99 vs. $150.49). However, Apixaban showed higher total QALYs gained compared to others (0.134 vs. 0.133 and 0.116). The incremental cost-effectiveness ratio for comparing Apixaban to Warfarin was calculated at -1332.83 cost per QALY, below the threshold of $11 134, indicating Apixaban's cost-effectiveness. Sensitivity analyses confirmed the robustness of the findings, with ICER consistently remaining below the threshold. Over 5 years (2024-2028) of Apixaban usage, the incremental cost starts at USD 70 250 296 in the first year and gradually rises to USD 71 770 662 in the fifth year. DSA and PSA were assessed to prove the robustness of the results., Conclusion: This study shows that Apixaban is a cost-effective option for stroke prevention in non-valvular atrial fibrillation patients in Iran compared to Warfarin., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals LLC.)

Venous thromboembolism is a preventable cause of postoperative mortality in patients undergoing surgery for malignancy. Current standard of care based on international guideline recommends 28 days of extended thromboprophylaxis after major abdominal and pelvic surgery for malignancies with unfractionated heparin or low molecular weight heparin. Direct oral anticoagulants have been approved for the treatment of venous thromboembolism in the general population. This regimen has a significant advantage over other types of anticoagulation regimens, particularly being administered by non-parenteral routes and without the need for laboratory monitoring. In this review, we evaluate the role of direct anticoagulation and provide an update on completed and ongoing clinical trials., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Atrial fibrillation (AF) can lead to a significant health and economic burden to society. This study aimed to assess the net budget impact of direct-acting oral anticoagulants (DOACs) instead of warfarin for stroke prevention in patients with non-valvular AF from the payer's perspective., Methods: A budget model over a 5-year period was used. Dabigatran 150 mg, dabigatran 110 mg, apixaban 5 mg, rivaroxaban 20 mg, edoxaban 60 mg, and edoxaban 30 mg were included. Inputs were retrieved from published literature. Adoption rate of DOACs started at 5% and subsequently had a 5% increase in each year. Net budget impact (NBI) and sensitivity analyses were performed., Results: The average NBI over the 5-year horizon for all DOACs ranged from 12.3 M USD to 13.9 M USD. Dabigatran 150 mg had the highest NBI, while edoxaban 30 mg had the lowest NBI. The average NBI/patient/year ranged from 63.03 USD - 70.75 USD., Conclusions: Of all DOACs, edoxaban 30 mg, apixaban 5 mg, and edoxaban 60 mg are the top 3 lowest NBI. Together with cost-effectiveness evidence, those DOACs should be considered to be listed on the National List of Essential Medicine in Thailand.

Abstract: Limited literature has established the role of direct oral anticoagulants (DOAC) for elderly patients with nonvalvular atrial fibrillation who are unsuited for warfarin. Therefore, the objectives of this study were to assess the effectiveness and safety of DOAC use in this vulnerable patient population. This was a retrospective propensity score matching cohort study. Among all patients aged 75+ years who were not candidates for warfarin, we matched those who initiated DOAC between September 2017 and September 2018 with those who did not receive DOAC or warfarin in a 1:1 ratio. Effectiveness outcome was a composite measure of stroke, transient ischemic attack, and pulmonary embolism. Safety outcome was a composite measure of non-trauma-related intracranial hemorrhage and gastrointestinal bleed. Unless patients died or lost membership, follow-up period for the effectiveness outcome was until the end of 2019, whereas the safety outcome was for a period up to 1 year. Conditional logistic regression was used to analyze both outcomes. We identified 7818 patients who met the inclusion criteria and started DOAC, which matched to 7818 patients who did not receive anticoagulants. The mean age was 82.3 ± 5.1 years, and 51.5% male. The DOAC group had a lower hazard ratio of 0.37 (confidence interval, 0.24-0.57; P < 0.01) for composite effectiveness outcomes, whereas no difference in the composite safety outcome (hazard ratio, 0.91; confidence interval, 0.65-1.25; P = 0.55) when compared with matched control. In conclusion, DOAC was found to be effective in preventing thromboembolic events in patients aged 75+ years with nonvalvular atrial fibrillation who were not eligible for warfarin., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Apixaban (2.5 mg) taken twice daily has been shown to substantially reduce the risk of venous thromboembolism (VTE) compared with placebo for the primary thromboprophylaxis of ambulatory patients with cancer who are starting chemotherapy and are at intermediate-to-high risk of VTE. We aimed to compare the health system costs and health benefits associated with primary thromboprophylaxis using apixaban with those associated with the current standard of care (where no primary thromboprophylaxis is given), from the perspective of Canada's publicly funded health care system in this subpopulation of patients with cancer over a lifetime horizon., Methods: We performed a cost-utility analysis to estimate the incremental cost per quality-adjusted life-year (QALY) gained with primary thromboprophylaxis using apixaban. We obtained baseline event rates and the efficacy of apixaban from the Apixaban for the Prevention of Venous Thromboembolism in High-Risk Ambulatory Cancer Patients (AVERT) trial on apixaban prophylaxis. We estimated relative risk for bleeding, risk of complications associated with VTE treatment, mortality rates, costs and utilities from other published sources., Results: Over a lifetime horizon, apixaban resulted in lower costs to the health system (Can$7902.98 v. Can$14 875.82) and an improvement in QALYs (9.089 v. 9.006). The key driver of cost-effectiveness results was the relative risk of VTE as a result of apixaban. Results from the probabilistic analysis showed that at a willingness to pay of Can$50 000 per QALY, the strategy with the highest probability of being most cost-effective was apixaban, with a probability of 99.87%., Interpretation: We found that apixaban is a cost-saving option for the primary thromboprophylaxis of ambulatory patients with cancer who are starting chemotherapy and are at intermediate-to-high risk of VTE., Competing Interests: Competing interests: Marc Carrier has received consulting fees from Bayer, Sanofi, Servier, BMS, Pfizer, Leo Pharma and Valeo. Philip Wells has received personal fees in the form of payment or honoraria from the Bristol Myers Squibb (BMS)–Pfizer Alliance, Sanofi, Bayer Healthcare and Medscape. He is also the board director for the Bruyère Research Institute and Ottawa Department of Medicine Not-for-Profit Corporation. No other competing interests were declared., (© 2021 CMA Joule Inc. or its licensors.)

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.

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., (© 2020 John Wiley & Sons Ltd.)

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.

Objectives: Several direct oral anticoagulants (DOACs) have been approved by the European Medicines Agency since 2008. The aim of the present cost-effectiveness-analysis was to analyze apixaban compared to other DOACs and vitamin K antagonists (warfarin) in Austria., Methods: A cost-utility-model was developed to simulate lifetime-costs and quality-adjusted-life-years of DOACs and warfarin, based on a published Markov-Model and 23 randomized trials with 94,656 atrial-fibrillation (AF) patients. Each year, a patient has a probability of suffering a clinically relevant (extracranial) bleed, an intracranial hemorrhage (ICH), an ischemic stroke or a myocardial infarction (MI), remaining healthy, or deceasing. Direct-costs (2018€) were derived from published sources from the payer's perspective., Results: In the base-case, warfarin had the lowest cost of 12,968 € (95%-CI±593 €) followed by apixaban (15,269 €±661 €), edoxaban (15,534 €±641 €), dabigatran (15,687 €±667 €), and rivaroxaban (17,522 €±764 €). Apixaban had the highest quality-adjusted-life-years estimate at 5.45 (SD, 0.06). In a Monte-Carlo probabilistic sensitivity analysis, apixaban was cost-effective vs. edoxaban, dabigatran, warfarin, and rivaroxaban in 85.6%, 79.0%, 76.4%, and 61.2% of the simulations, respectively., Conclusion: In patients with AF and an increased risk of stroke, prophylaxis with apixaban was highly cost-effective from the perspective of the Austrian health-care system.

Background: In patients with atrial fibrillation, incomplete adherence to anticoagulants increases risk of stroke. Non-warfarin oral anticoagulants (NOACs) are expensive; we evaluated whether higher copayments are associated with lower NOAC adherence., Methods: Using a national claims database of commercially-insured patients, we performed a cohort study of patients with atrial fibrillation who newly initiated a NOAC from 2012 to 2018. Patients were stratified into low (<$35), medium ($35-$59), or high (≥$60) copayments and propensity-score weighted based on demographics, insurance characteristics, comorbidities, prior health care utilization, calendar year, and the NOAC received. Follow-up was 1 year, with censoring for switching to a different anticoagulant, undergoing an ablation procedure, disenrolling from the insurance plan, or death. The primary outcome was adherence, measured by proportion of days covered (PDC). Secondary outcomes included NOAC discontinuation (no refill for 30 days after the end of NOAC supply) and switching anticoagulants. We compared PDC using a Kruskal-Wallis test and rates of discontinuation and switching using Cox proportional hazards models., Results: After weighting patients across the 3 copayment groups, the effective sample size was 17,558 patients, with balance across 50 clinical and demographic covariates (standardized differences <0.1). Mean age was 62 years, 29% of patients were female, and apixaban (43%), and rivaroxaban (38%) were the most common NOACs. Higher copayments were associated with lower adherence (P < .001), with a PDC of 0.82 (Interquartile range [IQR] 0.36-0.98) among those with high copayments, 0.85 (IQR 0.41-0.98) among those with medium copayments, and 0.88 (IQR 0.41-0.99) among those with low copayments. Compared to patients with low copayments, patients with high copayments had higher rates of discontinuation (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.08-1.19; P < .001)., Conclusions: Among atrial fibrillation patients newly initiating NOACs, higher copayments in commercial insurance were associated with lower adherence and higher rates of discontinuation in the first year. Policies to lower or limit cost-sharing of important medications may lead to improved adherence and better outcomes among patients receiving NOACs., Competing Interests: Disclosures BNR has received consulting fees from Blue Cross Blue shield of Massachusetts and the non-profit Alosa Health for unrelated work. JJG has received salary support from grants from Eli Lilly and Company and Novartis Pharmaceuticals Corporation to the Brigham and Women's Hospital and was a consultant to Optum, Inc., all for unrelated work. The other authors have no conflicts of interest to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To assess temporal clinical and budget impacts of changes in atrial fibrillation (AF)-related prescribing in England., Methods: Data on AF prevalence, AF-related stroke incidence and prescribing for all National Health Service general practices, hospitals and registered patients with hospitalised AF-related stroke in England were obtained from national databases. Stroke care costs were based on published data. We compared changes in oral anticoagulation prescribing (warfarin or direct oral anticoagulants (DOACs)), incidence of hospitalised AF-related stroke, and associated overall and per-patient costs in the periods January 2011-June 2014 and July 2014-December 2017., Results: Between 2011-2014 and 2014-2017, recipients of oral anticoagulation for AF increased by 86.5% from 1 381 170 to 2 575 669. The number of patients prescribed warfarin grew by 16.1% from 1 313 544 to 1 525 674 and those taking DOACs by 1452.7% from 67 626 to 1 049 995. Prescribed items increased by 5.9% for warfarin (95% CI 2.9% to 8.9%) but by 2004.8% for DOACs (95% CI 1848.8% to 2160.7%). Oral anticoagulation prescription cost rose overall by 781.2%, from £87 313 310 to £769 444 028, (£733,466,204 with warfarin monitoring) and per patient by 50.7%, from £293 to £442, giving an incremental cost of £149. Nevertheless, as AF-related stroke incidence fell by 11.3% (95% CI -11.5% to -11.1%) from 86 467 in 2011-2014 to 76 730 in 2014-2017 with adjustment for AF prevalence, the overall per-patient cost reduced from £1129 to £840, giving an incremental per-patient saving of £289., Conclusions: Despite nearly one million additional DOAC prescriptions and substantial associated spending in the latter part of this study, the decline in AF-related stroke led to incremental savings at the national level., Competing Interests: Competing interests: AO received speaker honoraria from Pfizer and provided consultancy to Daiichi Sankyo. CPG received speaker and/or consulting honoraria from AstraZeneca, Bayer, Novartis, Daiichi Sankyo, Bristol Myers Squibb, Menarini and Pfizer, and research grant funding from Abbott and Bristol Myers Squibb., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Direct-acting oral anticoagulants are indicated for the treatment of nonvalvular atrial fibrillation, but their use in patients after undergoing cardiac surgery is poorly defined despite a high prevalence of postoperative atrial fibrillation in this population., Methods: Patients diagnosed with postoperative atrial fibrillation were prospectively randomized to warfarin or apixaban. Safety, efficacy, and economic outcomes were evaluated until their 4- to 6-week postoperative appointment., Results: While this pilot study was not powered to determine a difference in safety or efficacy, adverse event rates were similar to the published literature. It was noted that a patient's course of therapy when utilizing apixaban was significantly less costly than warfarin when including medication, bridging, and laboratory expenses., Conclusion: Apixaban and warfarin both appeared to be safe and effective for anticoagulation throughout the duration of this pilot study in treating postoperative atrial fibrillation after coronary artery bypass grafting. Apixaban was associated with significantly less expense when bridging and monitoring costs were included in addition to medication expense.

Venous thromboembolism is highly prevalent in lung cancer patients. Low molecular weight heparins are recommended for long term treatment of cancer associated venous thromboembolism. Direct oral anticoagulants are however an interesting alternative as they are administered orally and don't require monitoring. There are currently studies comparing both their efficacy and tolerance for cancer patients and more and more guidelines suggest considering direct oral anticoagulants for cancer associated venous thromboembolism treatment. The objective of this study was to evaluate the budgetary impact that direct oral anticoagulants use would have for lung cancer associated venous thromboembolism treatment and prevention in France. An economic model was made to evaluate the cost of venous thromboembolism treatment and prevention among patients with primary lung cancer in France by two strategies: current guidelines versus direct oral anticoagulants use. The model was fed with clinical and economic data extracted from the French national health information system. The analysis was conducted from the national mandatory Health insurance point of view. The time horizon of the study was the evaluation of the annual management cost. Lung cancer associated venous thromboembolism management's mean cost was estimated of 836€ per patient, that is a total cost of about 40 million euros per year at a national level. A 76% decrease of this cost can be expected with direct oral anticoagulants use. However, despite their benefits, these treatments raise new issues (medication interactions, bleeding management), and would likely not be recommended for all patients.

Introduction: Direct-acting oral anticoagulants (DOACs) are associated with risk of major bleeding. This study evaluated the incremental healthcare economic burden of patients with atrial fibrillation (AF) treated with DOACs and hospitalized with a major bleed (MB)., Methods: Adult patients with AF treated with DOACs and hospitalized with MB or no MB hospitalizations during January 1, 2015-April 30, 2018 were extracted from MarketScan claims databases. The index date was defined as the first MB hospitalization for patients with MB and a random date during DOAC usage for patients without MB. Healthcare resource utilization and costs were evaluated for index hospitalizations of patients with MB and during the 6-month period prior to index dates and a variable follow-up period of 1-12 months for both patients with and those without MB. Multivariable regression analyses were performed to evaluate the incremental burden of MB vs. non-MB status on all-cause hospital days and healthcare costs., Results: Of the overall AF patient population using DOACs (N = 152,305), 7577 (5.0%) had a hospitalization for MB. Greater proportions of those who had an MB hospitalization were older and female compared to patients without MB (mean age 76.1 vs. 70.1 years; 44.1% vs. 40.5% female, respectively). For index MB hospitalizations, mean length of stay (LOS) was 5.3 days and cost was $32,938. In adjusted analyses, patients with MB had 3.6 more hospital days, $10,609 higher inpatient cost, $9613 higher outpatient medical cost, and $18,910 higher total healthcare costs for all causes per patient during follow-up (all p < 0.001). Including index MB hospitalization costs in the follow-up, all-cause total adjusted healthcare costs were almost two times higher for patients with vs. without MB ($96,590 vs. $49,091, p < 0.001)., Conclusions: Among a large US nationally representative sample of patients with AF treated with DOACs, the cost of MB hospitalization was substantial. Furthermore, healthcare costs following MB events were nearly 40% higher compared to those of patients with AF without an MB.

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., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Direct oral anticoagulants (DOACs) have quickly become attractive alternatives to the long-standing standard of care in anticoagulation, vitamin K antagonist. DOACs are indicated for prevention and treatment of several cardiovascular conditions. Since the first approval in 2010, DOACs have emerged as leading therapeutic alternatives that provide both clinicians and patients with more effective, safe, and convenient treatment options in thromboembolic settings. With the expanding role of DOACs, clinicians are faced with increasingly complex decisions relating to appropriate agent, duration of treatment, and use in special populations. This review will provide an overview of DOACs and act as a practical reference for clinicians to optimize DOAC use among common challenging scenarios. Topics addressed include (1) appropriate indications; (2) use in patients with specific comorbidities; (3) monitoring parameters; (4) transitioning between anticoagulant regimens; (5) major drug interactions; and (6) cost considerations.

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.

Objectives: Venous thromboembolism (VTE) incurs substantial costs to the UK National Health Service (NHS). Betrixaban is approved in the US for VTE prophylaxis with a recommended 35-42 days of treatment. This analysis modeled the budget impact of introducing betrixaban for extended-duration VTE prophylaxis in nonsurgical patients with acute medical illness at risk of VTE in the UK, where it is not yet licensed., Methods: The 5-year budget impact of introducing betrixaban into current prophylaxis (low molecular weight heparin and fondaparinux) was estimated for the UK NHS. The Phase 3 APEX study provided primary event (VTE, myocardial infarction, ischemic stroke, and death; all-cause or VTE-related) and treatment complications data. Literature informed risk of recurrent events and long-term complications, population, market share, and costs for treatment and management of events. Network meta-analyses informed symptomatic DVT, pulmonary embolism and VTE-related death rates in fondaparinux patients. Deterministic sensitivity analyses explored uncertainty., Results: Introducing betrixaban accrued savings of £1,290,000-£23,000,000 in years 1-5. Savings were from reduced primary VTE events, which reduced recurrent events and future complications. All sensitivity analyses showed savings., Conclusion: Introducing extended-duration VTE prophylaxis with betrixaban in the UK would accrue substantial savings annually over the next 5 years compared to current prophylaxis. Clinical trial registration: www.clinicaltrials.gov identifier is NCT01583218.

Background: Administrative data were used to investigate changes in hospitalizations for atrial fibrillation (AF), AF-related stroke, and treatment patterns between 2012 and 2016., Methods: From the 'Ricerca e Salute' database, a population- and patient-based repository involving >12 million inhabitants and linking demographics, prescriptions, and hospital discharge records, all patients discharged alive with a diagnosis of AF between 2012 and 2015 were followed for 1 year., Results: A total of 194,030 AF patients were included. The number of AF cases increased ~10% over time, from 4.0 per 1,000 inhabitants in 2012 to 4.4 per 1,000 in 2015. At 1 year, hospitalizations for ischemic stroke decreased from 21.3 per 1,000 patients with AF in 2012-2013 to 14.7 per 1,000 in 2015-2016 (-31%, 95% CI -18 to -41). Over the same period, oral anticoagulant (OAC) use increased from 56.7% to 64.4% (+14%, 95% CI +8 to +26), vitamin K antagonist use decreased (from 55.9 to 36.7%; -34%, 95% CI -21 to -44), whereas direct OACs (DOACs) increased (from <1% in 2012 to 27.7% in 2015). Antiplatelet prescriptions fell from 42.6% in 2012 to 28.1% in 2015. Hospitalizations for major bleeds, mainly gastrointestinal, increased from 1.5‰ in 2012-2013 to 2.3‰ in 2015-2016, whereas hemorrhagic stroke admissions decreased from 6.5‰ to 4.1‰., Conclusions: There was a slight increase in the prevalence of AF between 2012 and 2015, whereas the overall use of antiplatelet agents decreased and that of OAC, particularly DOACs, increased. Over the same period, 1-year hospitalizations for ischemic stroke declined substantially, with a declining rate of hemorrhagic strokes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: It has been reported that oral anticoagulation (OAC) is underused among Chinese patients with non-valvular atrial fibrillation (NVAF). Non-vitamin K antagonist oral anticoagulants (NOAC) have been recommended by recent guidelines and have been covered since 2017 by the Chinese medical insurance; thus, the overall situation of anticoagulant therapy may change. The aim of this study was to explore the current status of anticoagulant therapy among Chinese patients with NVAF in Jiangsu province., Methods: This was a multi-center, cross-sectional study that was conducted in seven hospitals from January to September in 2017. The demographic characteristics and medical history of the patients were collected by questionnaire and from the medical records. Multivariate logistic regression was used to identify factors associated with anticoagulant therapy., Results: A total of 593 patients were included in the analysis. A total of 35.6% of the participants received OAC (11.1% NOAC and 24.5% warfarin). Of those patients with a high risk of stroke, 11.1% were on NOAC, 24.8% on warfarin, 30.6% on aspirin, and 33.6% were not on medication. Self-paying, duration of AF ≥5 years were negatively associated with anticoagulant therapy in all patients (OR 1.724, 95% CI 1.086~2.794; OR 1.471, 95% CI 1.006~2.149, respectively), whereas, permanent AF was positively associated with anticoagulant therapy (OR 0.424, 95% CI 0.215~0.839). Among patients with high risk of stroke, self-paying and increasing age were negatively associated with anticoagulant therapy (OR 2.305, 95% CI 1.186~4.478; OR 1.087, 95% CI 1.041~1.135, respectively)., Conclusions: Anticoagulant therapy is positively associated with permanent AF and negatively associated with self-paying, duration of AF > 5 years. Furthermore, the current status of anticoagulant therapy among Chinese patients with NVAF in Jiangsu province does not appear optimistic. Therefore, further studies should focus on how to improve the rate of OAC use among NVAF patients. In addition, policy makers should pay attention to the economic situation of the patients with NVAF using NOAC., Trial Registration: 2,017,029. Registered 20 March 2017 (retrospectively registered).

Andexanet-alpha is a specific reversal agent for direct factor Xa inhibitors (dFXaI). We aimed to project utilization rates and cost of andexanet for reversal of dFXaI-related major hemorrhage compared to 4-factor prothrombin complex concentrates (4F-PCC). A retrospective, multicenter review was conducted between 1/1/2014 and 7/15/2018 of patients who received 4F-PCC for reversal of dFXaI-related life-threatening hemorrhages. Total hospital reimbursements/patient were calculated based on national average MS-DRG payments adjusting for Medicare discounts. The projected cost for andexanet (based on dose and insurance) and % reimbursement/patient was compared to the actual cost of 4F-PCC. Hemostasis at 24 h (excellent/good vs. poor) and 30-day thrombotic complications were assessed. Of 126 patients who received 4F-PCC to reverse dFXaI, 46 (~ 10 per-year) met inclusion criteria. The median projected cost of andexanet was $22,120/patient, compared to $5670/patient for 4F-PCC (P < 0.001). The median hospital reimbursement was $11,492/hospitalization. The projected cost of andexanet alone would exceed the entire hospital reimbursement in 74% of patients by a median of $7604, while 4F-PCC cost exceeded the total hospital payments in 7% of patients in the same cohort (P < 0.001). Hemostasis was excellent/good in 72% of patients post-4F-PCC, compared to 82% in andexanet trials. Thromboembolic events occurred in 4% of patients following 4F-PCC versus 10% in andexanet trials. The projected cost of andexanet would exceed the national average hospital reimbursement/patient in nearly 75% of patients by over $7500/hospitalization. 4F-PCC was significantly less expensive, had lower rates of thrombosis, but also lower rates of good/excellent hemostasis compared to published data for andexanet.

Background: Anticoagulation therapy is recommended for stroke prevention in high-risk patients with atrial fibrillation (AF). This study aimed to estimate the time to switch from warfarin to a direct oral anticoagulant (DOAC) and identify the factors associated with it., Methods: By using claims data, we studied 7111 warfarin-using patients with nonvalvular AF who were aged ≥65 years. The Kaplan-Meier analysis was performed to estimate the time to switch from warfarin to a DOAC, and Cox proportional hazard regression analysis was used to estimate the influencing factors., Results: Approximately one-third of the patients (2403, 33.8%) switched from warfarin to a DOAC during the study period. Female sex, aged between 75 and 79 years, having a Medical Aid or Patriots and Veterans Insurance, hypertension, and history of prior stroke, and transient ischemic attack or thromboembolism (prior stroke/TIA/TE) were associated with a significantly shorter time to switch. The odds of switching to a DOAC were increased by approximately 1.2-fold in the women and 1.4-fold in the patients with prior stroke/TIA/TE., Conclusions: Approximately one-third of the warfarin-using patients switched from warfarin to a DOAC within 6 months after the change in the DOAC reimbursement criteria. In the Cox proportional hazard regression analysis, the factors that affected anticoagulant switching from warfarin to a DOAC were female sex and history of prior stroke/TIA/TE.

Direct oral anticoagulants (DOAC) are first line treatment for pulmonary embolism (PE). Treatment of acute PE is traditionally hospital based and associated with high costs. The aims of this study were to evaluate potential cost savings with outpatient DOAC treatment compared to inpatient DOAC treatment in patients with low risk PE. A retrospective study in patients with DOAC treated low risk PE (simplified pulmonary severity index [sPESI] ≤ 1) admitted to 8 hospitals during 2013-2015. Health care costs were compared in 223(44%) patients treated as outpatients and 287(56%) treated in hospital. Total cost per patient was 8293 EUR in the inpatient group, and 2176 EUR in the outpatient group (p < 0.001). Total costs for inpatients were higher (p < 0.001) compared to outpatients in both subgroups with sPESI 0 and 1. In multivariate analysis, type of treatment (in- or outpatient, p = < 0.001) and sPESI group (0 or 1, p = < 0.001) were associated with total cost below or above median, whereas age (p = 0.565) and gender (p = 0.177) was not. Adherence to guidelines recommending outpatient treatment with DOAC in patients with low risk PE enables significant savings.

Most atrial fibrillation (AF) patients need anticoagulation management to reduce the risk of thromboembolic events and stroke. Currently, two major drug therapies are available: warfarin and direct oral anticoagulant (DOAC). This study examined the spatial costs of these therapies and derived the least-cost market areas for both therapies in the study area. The concepts of spatial costs and the principles of forming market areas were used as theoretical starting points, and the patients' travel, time-loss, and medication cost parameters combined with geographical information systems methods were incorporated into the geospatial model. Results showed that for AF patients who live near the international normalized ratio (INR) monitoring sample collection point and have less than 15 annual INR monitoring visits, warfarin therapy resulted in the lowest cost regardless of patient's travel mode and their assumed working or retirement status. If the AF patient needs more frequent INR monitoring visits or lives farther from the nearest sample collection point, DOAC would be the least costly option. The modelled results reveal the variety and importance of patients' cost of time loss and travel costs when a physician selects the appropriate anticoagulation therapy.

Warfarin remains the most commonly prescribed oral anticoagulant in the United States, but it has disadvantages such as dietary interactions and frequent laboratory monitoring. Direct oral anticoagulants (DOACs) have been introduced as safer and equally effective alternatives to warfarin. This study assessed patient preference for warfarin or DOAC based on a willingness to pay more for potential DOAC benefits. Current warfarin patients with atrial fibrillation or venous thromboembolism enrolled in the University of Utah Health Thrombosis Service were given a one-time electronic survey that assessed preferences between warfarin and DOACs using scenarios comparing effectiveness, safety, and convenience. When DOACs were preferred, patients were asked how much more they would be willing to pay monthly for the perceived advantages associated with DOACs. With 123 completed surveys, 68% of patients preferred to stay on warfarin. No particular factor influenced patient preference (lack of routine laboratory monitoring, lower risks of major bleeding, and fewer dietary interactions). Reduced stroke risk was associated with the highest value (willing to pay an additional $21). Considering all factors, patients preferring DOACs would pay a median $18 extra per month for the additional benefits. Prior exposure to DOACs was associated with preference for DOACs. Many patients currently taking warfarin preferred to stay on warfarin when given the choice, despite DOAC benefits. Willingness to pay extra for DOAC advantages did not exceed $20 in the majority of survey respondents. Previous DOAC exposure influences patient preference and perceived value for DOACs.

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., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To assess long-term healthcare costs related to ischemic stroke and systemic embolism (stroke/SE) and major bleeding (MB) events in patients with non-valvular atrial fibrillation (NVAF) treated with non-vitamin K antagonist oral anticoagulants (NOACs). Materials and methods: Optum's Clinformatics Data Mart database from 1/2009-12/2016 was analyzed. Adult patients with ≥1 stroke/SE hospitalization (index date) were matched 1:1 to patients without stroke/SE (random index date), based on propensity scores. Patients with an MB event were matched to patients without MB. All patients had an NOAC dispensing overlapping index date, ≥12 months of eligibility pre-index date, and ≥1 NVAF diagnosis. The observation period spanned from the index date until the earliest date of death, switch to warfarin, end of insurance coverage, or end of data availability. Mean costs were evaluated: (1) per-patient-per-year (PPPY) and (2) at 1, 2, 3, and 4 years using Lin's method. Results: The cost differences were, respectively, $48,807 and $28,298 PPPY for NOAC users with stroke/SE ( n =  1,340) and those with MB ( n =  3,774) events compared to controls. Cost differences of patients with vs without stroke/SE were $49,876, $51,627, $57,822, and $60,691 at 1, 2, 3, and 4 years post-index, respectively ( p  < 0.001). These cost differences were $31,292, $35,658, $44,069, and $47,022 for patients with vs without MB after 1, 2, 3, and 4 years post-index, respectively ( p  < 0.001). Limitations: Limitations include unobserved confounders, coding and/or billing inaccuracies, limited sample sizes over longer follow-up, and the under-reporting of mortality for deaths occurring after 2011. Conclusions: The incremental healthcare costs incurred by patients with vs without stroke/SE was nearly twice as high as those of patients with vs without MB. Moreover, each additional year up to 4 years after the first event was associated with an incremental cost for patients with a stroke/SE or MB event compared to those without an event.

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background Recent publications reached conflicting conclusions about the cost-effectiveness of left atrial appendage closure (LAAC) with the Watchman device (Boston Scientific, Marlborough, MA) for stroke risk reduction in nonvalvular atrial fibrillation (AF). This analysis sought to assess the cost-effectiveness of LAAC relative to both warfarin and nonwarfarin oral anticoagulants (NOACs) using pooled, long-term data from the randomized PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) and PREVAIL (Prospective Randomized Evaluation of the Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long-Term Warfarin) trials. Methods and Results A Markov model was constructed from a US payer perspective with a lifetime (20-year) horizon. LAAC clinical event rates and stroke outcomes were from pooled PROTECT AF and PREVAIL trial 5-year data. Warfarin and NOAC inputs were derived from published meta-analyses. The model was populated with a cohort of 10 000 patients, aged 70 years, at moderate stroke and bleeding risk. Sensitivity analyses were performed. LAAC was cost-effective relative to warfarin by year 7 ($48 674/quality-adjusted life-year) and dominant (more effective and less costly) by year 10. LAAC became cost-effective and dominant compared with NOACs by year 5. Over a lifetime, LAAC provided 0.60 more quality-adjusted life-years than warfarin and 0.29 more than NOACs. In sensitivity analyses, LAAC was cost-effective relative to warfarin and NOACs in 98% and 95% of simulations, respectively. Conclusions Using pooled, 5-year PROTECT AF and PREVAIL trial data, LAAC proved to be not only cost-effective, but cost saving relative to warfarin and NOACs. LAAC with the Watchman device is an economically viable stroke risk reduction strategy for patients with AF seeking an alternative to lifelong anticoagulation.

Background: Apixaban, an oral anticoagulant for stroke and systemic embolism prevention in non-valvular atrial fibrillation (NVAF), was superior to warfarin in prevention of stroke and systemic embolism, bleeding outcomes and mortality (ARISTOTLE trial), and substantially reduced stroke risk, with no significant increase in major or intracranial bleeding risk versus aspirin (AVERROES trial)., Objective: Estimate cost-effectiveness of apixaban versus other anticoagulants for NVAF treatment in Saudi Arabia., Design: Lifetime Markov model., Setting: A published model was adapted from the United Kingdom (UK) to the Saudi Arabia setting., Patients and Methods: The model enabled pairwise comparisons of apixaban against other anticoagulants, aspirin, and aspirin+clopidogrel. Apart from warfarin and aspirin, comparisons were indirect. Subpopulations included vitamin K antagonist (VKA) suitable and unsuitable patients. Medication and physician visit costs were from published lists. A cost ratio (0.533), from comparison of UK and Saudi physician visit costs, was applied to UK model inputs to estimate local event costs. Background life expectancy was from Saudi life tables. Model structure, treatment comparators, patient characteristics, event rates, and utilities were unchanged. Costs and health benefits were discounted by 3.5% annually., Main Outcome Measure: Incremental cost-effectiveness ratio of cost per quality-adjusted life-year (QALY) gained., Sample Size: Model cohort of 1000 NVAF patients, for VKA suitable and VKA unsuitable populations., Results: Apixaban was dominant versus warfarin (VKA suitable) and rivaroxaban (VKA suitable and unsuitable). Compared against dabigatran (110mg, 150 mg, 110/150mg), the cost/QALY gained for apixaban was $5166, $11 143, $10 849 (VKA suitable) and $5 157, $14 424, $14 134 (VKA unsuitable), respectively. Cost/QALY for apixaban versus aspirin and aspirin+clopidogrel was $14 805 and $5784 (VKA suitable); and $10 564 and $4203 (VKA unsuitable), respectively. Sensitivity analyses demonstrated consistency of findings across varying inputs., Conclusions: Apixaban was found to be cost-effective for stroke prevention among Saudi NVAF patients, when assessed using a US$20 000 willingness-to-pay threshold., Limitations: Lack of robust local clinical, cost and utility data for model inputs. Lack of head-to-head clinical trial data for rivaroxaban, dabigatran, and clopidogrel plus aspirin comparators., Conflict of Interest: Study was funded by Pfizer Inc. and Bristol Myers-Squibb. KO, RS, SAK and AAA received salaries from their respective employers, but did not receive direct financial compensation for participation in or authorship of this study.

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/m 2 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., (Copyright © 2019 Janssen Scientific Affairs, LLC. Published by Elsevier Inc. All rights reserved.)

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.

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 (CHADS 2 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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: Peripheral artery disease affects 1.2% of the population globally and is associated with an increased risk of atherothrombotic cardiovascular events, major adverse limb events and mortality. The Cardiovascular Outcomes for People Using Anti-coagulation Strategies (COMPASS) trial demonstrated positive results of rivaroxaban plus aspirin therapy compared to aspirin therapy alone in those with peripheral artery disease or carotid artery disease. We sought to estimate the cost-effectiveness from the Australian healthcare system perspective., Methods and Results: A Markov model was developed to simulate the experiences of a hypothetical population of 1000 individuals with peripheral artery disease or carotid artery disease, profiled on the COMPASS trial, treated with rivaroxaban plus aspirin therapy versus aspirin therapy alone. With each annual cycle, individuals were at risk of having non-fatal cardiovascular disease events, major adverse limb events, or dying. Individuals were also at risk of non-fatal major bleeding. The model had a lifetime time horizon. Costs and utilities were sourced from the literature and discounted at 5.0% annually. Rivaroxaban plus aspirin therapy prevented 143 non-fatal cardiovascular disease events, 118 major adverse limb events and 10 deaths compared to aspirin therapy alone. Conversely, 156 additional major non-fatal bleeds were accrued. With an additional 256 quality-adjusted life years gained, at an additional cost of AUD$6,858,103, the incremental cost-effectiveness ratio was AUD$26,769 (discounted) per quality-adjusted life year gained, which is below Australia's arbitrary willingness to pay threshold of AUD$50,000., Conclusion: In those with peripheral artery disease or carotid artery disease, rivaroxaban plus aspirin therapy is effective and cost-effective in the prevention of recurrent cardiovascular disease compared to aspirin therapy alone.

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.

Aims: The EdoxabaN vs. warfarin in subjectS UndeRgoing cardiovErsion of atrial fibrillation (ENSURE-AF) (NCT02072434) study was a multicentre prospective, randomized, open-label, blinded-endpoint evaluation (PROBE) trial comparing edoxaban with enoxaparin/warfarin followed by warfarin alone in 2199 non-valvular atrial fibrillation patients undergoing electrical cardioversion and showed comparable rates of bleeding and thromboembolism between treatments. This prespecified ancillary analysis investigated the impact of edoxaban therapy on treatment satisfaction and utilization of healthcare services., Methods and Results: The Perception of Anticoagulant Treatment Questionnaire (PACT-Q2) was completed by study patients on Day 28 post-cardioversion. Higher scores represent greater satisfaction. Healthcare resource utilizations were collected from randomization to Day 28 post-cardioversion. Data from patients who received at least one dose of study drugs were analysed. Patients treated with edoxaban were more satisfied than enoxaparin/warfarin in both PACT-Q treatment satisfaction and convenience scores (P < 0.001 for both). Differences in treatment satisfaction scores were greater in patients who underwent non-transoesophageal echocardiography (TOE)-guided cardioversion than in patients who underwent TOE-guided cardioversion. Edoxaban was associated with fewer clinic visits (4.75 visits vs. 7.60 visits; P < 0.001) and fewer hospital days (3.43 days vs. 5.41 days; P < 0.05). Rates of hospitalizations and emergency room visits were not significantly different. Overall, edoxaban therapy was estimated to reduce healthcare costs by €107.73, €437.92, €336.75, and $246.32 per patient in German, Spanish, Italian, and US settings, respectively., Conclusions: The convenience of edoxaban therapy over warfarin in patients undergoing cardioversion may provide greater treatment satisfaction and cost savings to the healthcare system.

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., (Copyright © 2018 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objective: Our objective was to evaluate the association between switching from warfarin to non-vitamin K oral anticoagulants (NOACs) and potential drug-drug interactions (DDIs), healthcare utilization, and expenditures in working-age adults with atrial fibrillation (AF)., Methods: We conducted a retrospective cohort study using data from 2010 to 2015 for patients who switched from warfarin to NOACs (switchers) and those who continued to receive warfarin (non-switchers). We identified medications known or suspected to have clinically significant interactions with NOACs or warfarin. We used multivariate logistic regression, negative binomial, and generalized linear models to evaluate the influence of switching to NOACs and of potential DDIs on inpatient visits, outpatient visits, number of outpatient visits, and non-drug medical expenditures. Inverse probability of treatment weighting was also applied in analyses., Results: A total of 4126 patients with AF were included in the study. Switching to NOACs was significantly and negatively related to the number of outpatient, inpatient, and emergency room (ER) visits and non-drug medical expenditures. When potential DDIs were included in the models, switching remained significantly associated only with reduced inpatient and outpatient visits. Notably, having at least one potential DDI was associated with an increased likelihood of ER visits and the number of outpatient visits; it was also significantly and positively associated with non-drug medical expenditures., Conclusions: Relative to persistent warfarin use, switching to NOACs was associated with fewer inpatient, ER, and outpatient visits and lower non-drug costs. Potential DDIs were also strongly and positively associated with healthcare utilization and expenditures. Both are critical to consider in the management of AF in working-age adults.

Objective: In light of the Cardiovascular Outcomes for People using Anticoagulation Strategies (COMPASS) trial, our objective was to assess the cost-effectiveness, from the Australian healthcare perspective, of rivaroxaban in combination with aspirin versus aspirin alone for the prevention of recurrent cardiovascular disease among patients with stable atherosclerotic vascular disease., Methods: A Markov model was developed using input data from the COMPASS trial to predict the clinical course and costs of patients over a 20-year time-horizon. The model comprised of three health states: 'Alive without recurrent CVD', 'Alive after recurrent CVD' and 'Dead'. Costs were from the Australian public healthcare system perspective, and estimated from published sources, as were utility data. The costs of rivaroxaban were based on current acquisition prices on the Australian Pharmaceutical Benefits Schedule (PBS) and assumed as AUD$3.09/day. The main outcome of interest was the incremental cost-effectiveness ratio (ICER) in terms of cost per quality adjusted life year (QALY) gained, and cost per year of life saved (YoLS). Costs and benefits were discounted by 5.0% per year., Results: Compared to aspirin alone, rivaroxaban plus aspirin was estimated to cost an additional AUD$12,156 (discounted) per person, but lead to 0.516 YoLS (discounted) and 0.386 QALYs gained (discounted), over 20 years. These equated to ICERs of AUD$23,560/YoLS and AUD$31,436/QALY gained. We have assumed a threshold of AUD$50,000/QALY gained to signify cost-effectiveness., Conclusion: Compared to aspirin, rivaroxaban in combination with aspirin is likely to be cost-effective in preventing recurrent cardiovascular events in patients with stable atherosclerotic vascular disease., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Electrical cardioversion (ECV) is a procedure in which a direct current electric shock is used to quickly and effectively restore the normal sinus rhythm. Appropriate anticoagulation reduces the risk of embolic events during and after ECV. The aim of this study was to estimate the cost-effectiveness of rivaroxaban compared with vitamin K oral antagonists (VKAs) in patients with atrial fibrillation undergoing elective ECV in the Netherlands., Methods and Results: A static transmission model over a 1-year time horizon was developed to compare rivaroxaban with VKAs in terms of clinical outcomes, health effects (quality-adjusted life years; QALYs), and costs. Cost-effectiveness was assessed from a societal and health care payer perspective at a willingness-to-pay level of €20,000 per QALY gained. The use of rivaroxaban as an anticoagulant in patients with atrial fibrillation scheduled for ECV would lead to a health gain of 0.23 QALYs per patient and would cost €1.83 per patient from the societal perspective, resulting in an incremental cost-effectiveness ratio of €7.92 per QALY gained. The probability of rivaroxaban being cost-saving compared with VKAs was 49.6% from this perspective. From the health care payer perspective, the incremental cost would be €509 per patient with a health gain of 0.23 QALYs per patient, resulting in an incremental cost-effectiveness ratio of €2198 per QALY gained., Conclusions: The use of rivaroxaban in elective ECV is a cost-effective alternative to the use of VKAs. Rivaroxaban has a 50% probability of being cost-saving compared with VKAs and would increase a patient's quality of life when non-health care costs such as productivity loss and informal care costs are taken into account.

Background: Several studies have compared the cost effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin using results from clinical trials evaluating NOACs. However, the time in therapeutic range (TTR) of warfarin groups ranged across clinical trials, and all were below the therapeutic goal of 70%. We compared the cost effectiveness of edoxaban 60 mg, apixaban 5 mg, dabigatran 150 mg, dabigatran 110 mg, rivaroxaban 20 mg, and well-managed warfarin with a TTR of 70% in preventing stroke among patients with atrial fibrillation at high risk of bleeding., Methods: For the six treatments, we used a Markov state-transition model to quantify lifetime costs in $US and effectiveness in quality-adjusted life-years (QALYs). We simulated relative risk ratios of clinical events with each NOAC versus warfarin with a TTR of 70% using published regression models that predict how the incidence of thrombotic or hemorrhagic events changes for each unit change in TTR. We re-ran our analysis for two other estimates of TTR: 65 and 75%., Results: Treatment with edoxaban 60 mg cost $US127,520/QALY gained compared with warfarin with a TTR of 70% and cost $US41,860/QALY gained compared with warfarin with a TTR of 65%. However, warfarin with a TTR of 75% was more effective and less expensive than all NOACs. For three levels of TTR, apixaban 5 mg, dabigatran 150 mg, dabigatran 110 mg, and rivaroxaban 20 mg were dominated strategies., Conclusions: The comparative cost effectiveness of edoxaban and warfarin is highly sensitive to TTR. At the $US100,000/QALY willingness-to-pay threshold, our results suggest that warfarin is the most cost-effective treatment for patients who can achieve a TTR of 70%.

Introduction: Anticoagulants refer to a variety of agents that inhibit one or more steps in the coagulation cascade. Generally, clinical conditions that require the prescribing of an oral anticoagulant increase in frequency with age. However, a major challenge of anticoagulation use among older patients is that this group of patients also experience the highest bleeding risk. To date, economic evaluation of prescribing of anticoagulants that includes the novel or newer oral anticoagulants (NOACs) in older adults has not been conducted and is warranted., Areas Covered: A review of articles that evaluated the cost of prescribing conventional (e.g. vitamin K antagonists) and NOACs (e.g. direct thrombin inhibitors and direct factor Xa inhibitors) in older adults., Expert Commentary: While the use of NOACs significantly increases the cost of the initial treatment for thromboembolic disorders, they are still considered cost-effective relative to warfarin since they offer reduced risk of intracranial haemorrhagic events. The optimum anticoagulation with warfarin can be achieved by providing specialised care; clinics managed by pharmacists have been shown to be cost-effective relative to usual care. There are suggestions that genotyping the CYP2C9 and VKORC1 genes is useful for determining a more appropriate initial dose and thereby increasing the effectiveness and safety of warfarin.

Background: Rivaroxaban is the first novel oral anticoagulant to receive regulatory approval for non-valvular atrial fibrillation (NVAF) patients who require cardioversion. The MonaldiVert real life experience showed positive benefit-risk profile of short term rivaroxaban administration for transesophageal echocardiogram guided cardioversion in patients who had not achieved adequate pre-procedural vitamin K antagonist (VKA) anticoagulation., Methods: Aim of our study was to perform a budget impact analysis of MonaldiVert anticoagulation strategy for direct current cardioversion in NVAF patients and to compare the following costs borne by the Regional Healthcare System (RHS) with those for a hypothetical cohort of identical patients underwent from the beginning to early rivaroxaban treatment before direct current cardioversion., Results: The mean costs per each NVAF patient treated with VKA strategy and rivaroxaban rescue strategy were € 134.53 and € 189.83, respectively. Considering a hypothetical scenario in which all study population would be treated from the beginning with rivaroxaban (rivaroxaban early strategy), the mean cost per patient would have been € 81.11. The total cost borne by the RHS, including the cost of the cardioversion procedure, for the two therapeutic strategies carried out at Monaldi Hospital (VKA strategy and Rivaroxaban rescue strategy) was € 88,458.53. The total cost would be borne by the RHS for rivaroxaban early strategy, if applied to all study population, would have been € 69,989.15 with a saving of € 18,469.38 compared to the actually applied strategy., Conclusions: Rivaroxaban rescue strategy for transesophageal echocardiography guided direct current cardioversion in NVAF patients, who had not achieved adequate pre-procedural VKA anticoagulation, is an effective and safe strategy, which allows to not delay the procedure, reducing times and wastage of cardioversion slots, without substantial costs increase.