Non-warfarin oral anticoagulant copayments and adherence in atrial fibrillation: A population-based cohort study.

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.

Cost-effectiveness of antithrombotic agents for atrial fibrillation in older adults at risk for falls: a mathematical modelling study.

BACKGROUND: Antithrombotic drugs decrease stroke risk in patients with atrial fibrillation, but they increase bleeding risk, particularly in older adults at high risk for falls. We aimed to determine the most cost-effective antithrombotic therapy in older adults with atrial fibrillation who are at high risk for falls. METHODS: We conducted a mathematical modelling study from July 2019 to March 2020 based on the Ontario, Canada, health care system. We derived the base-case age, sex and fall risk distribution from a published cohort of older adults at risk for falls, and the bleeding and stroke risk parameters from an atrial fibrillation trial population. Using a probabilistic microsimulation Markov decision model, we calculated quality-adjusted life years (QALYs), total cost and incremental cost-effectiveness ratios (ICERs) for each of acetylsalicylic acid (ASA), warfarin, apixaban, dabigatran, rivaroxaban and edoxaban. Cost data were adjusted for inflation to 2018 values. The analysis used the Ontario public payer perspective with a lifetime horizon. RESULTS: In our model, the most cost-effective antithrombotic therapy for atrial fibrillation in older patients at risk for falls was apixaban, with an ICER of $8517 per QALY gained (5.86 QALYs at $92 056) over ASA. It was a dominant strategy over warfarin and the other antithrombotic agents. There was moderate uncertainty in cost-effectiveness ranking, with apixaban as the preferred choice in 66% of model iterations (given willingness to pay of $50 000 per QALY gained); edoxaban, 30 mg, was preferred in 31% of iterations. Sensitivity analysis across ranges of age, bleeding risk and fall risk still favoured apixaban over the other medications. INTERPRETATION: From a public payer perspective, apixaban is the most cost-effective antithrombotic agent in older adults at high risk for falls. Health care funders should implement strategies to encourage use of the most cost-effective medication in this population.

Cost-Effectiveness Analysis and Budget Impact: Antimuscarinics and Mirabegron for the Treatment of Patients With Urge Urinary Incontinence: The Brazilian Public Health System Perspective.

OBJECTIVES: The Brazilian public health system does not cover pharmacotherapy for urge urinary incontinence (UUI). The aim of this study was to estimate the cost-effectiveness and budget impact of providing tolterodine, solifenacin, oxybutynin (OXY), darifenacin, and mirabegron for the treatment of UUI in Brazilian public health system. METHODS: A cost-effectiveness analysis with budget impact was performed. Six scenarios were assessed: in one scenario, all 5 therapeutic alternatives approved for coverage, and in the remaining 5 scenarios, only 1 alternative is approved for adoption for all patients. Clinical data were derived from a rapid systematic review conducted in several databases. One-way sensitivity analysis was also performed. The time horizon was 12 months. RESULTS: The cost-effectiveness analysis showed that patients treated with OXY had the lowest incremental cost-effectiveness ratio (ICER) per outcomes assessed (change in urinary incontinence episodes (UIE): R$1180.08; change in urge incontinence episodes: R$757.85 and change in micturition frequency: R$907.75), corresponding to a budget impact of R$17.9 billion over 5 years. The change in effectiveness measures was the parameter that most influenced the results of the ICER per patient-year. CONCLUSION: The results of the study have shown that OXY and solifenacin had the lowest ICER per patient-year and the lowest budget impact when compared with other drugs.

Are Beta 3 Adrenergic Agonists Now the Preferred Pharmacologic Management of Overactive Bladder?

PURPOSE OF THE REVIEW: This paper discusses the recent evidence supporting beta 3 adrenergic agonists as the preferred pharmacological management of overactive bladder syndrome. RECENT FINDINGS: Mirabegron has a similar efficacy profile to first-line antimuscarinics with favorable adverse effects profile. Treatment of OAB with beta-3 adrenergic agonist should be favored in patients at higher risk of anticholinergic adverse events. The efficacy and tolerability of beta-3 adrenergic agonists are consistently reported in older OAB patients, whether used alone or with other antimuscarinics. Mirabegron is cost-effective in treating OAB unless the symptoms were severe or refractory. Combination therapy of mirabegron and other pharmacotherapy has proven to be efficient in controlling OAB symptoms without inducing serious add-on adverse effects. While beta-3 adrenergic agonists bear favorable advantages in OAB treatment, physicians should perform a thorough and careful pre-treatment planning to optimize treatment benefits and adherence.

Avatrombopag and lusutrombopag for thrombocytopenia in people with chronic liver disease needing an elective procedure: a systematic review and cost-effectiveness analysis.

BACKGROUND: There have been no licensed treatment options in the UK for treating thrombocytopenia in people with chronic liver disease requiring surgery. Established management largely involves platelet transfusion prior to the procedure or as rescue therapy for bleeding due to the procedure. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of two thrombopoietin receptor agonists, avatrombopag (Doptelet®; Dova Pharmaceuticals, Durham, NC, USA) and lusutrombopag (Mulpleta®; Shionogi Inc., London, UK), in addition to established clinical management compared with established clinical management (no thrombopoietin receptor agonist) in the licensed populations. DESIGN: Systematic review and cost-effectiveness analysis. SETTING: Secondary care. PARTICIPANTS: Severe thrombocytopenia (platelet count of < 50,000/µl) in people with chronic liver disease requiring surgery. INTERVENTIONS: Lusutrombopag 3 mg and avatrombopag (60 mg if the baseline platelet count is < 40,000/µl and 40 mg if it is 40,000-< 50,000/µl). MAIN OUTCOME MEASURES: Risk of platelet transfusion and rescue therapy or risk of rescue therapy only. REVIEW METHODS: Systematic review including meta-analysis. English-language and non-English-language articles were obtained from several databases including MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials, all searched from inception to 29 May 2019. ECONOMIC EVALUATION: Model-based cost-effectiveness analysis. RESULTS: From a comprehensive search retrieving 11,305 records, six studies were included. Analysis showed that avatrombopag and lusutrombopag were superior to no thrombopoietin receptor agonist in avoiding both platelet transfusion and rescue therapy or rescue therapy only, and mostly with a statistically significant difference (i.e. 95% confidence intervals not overlapping the point of no difference). However, only avatrombopag seemed to be superior to no thrombopoietin receptor agonist in reducing the risk of rescue therapy, although far fewer patients in the lusutrombopag trials than in the avatrombopag trials received rescue therapy. When assessing the cost-effectiveness of lusutrombopag and avatrombopag, it was found that, despite the success of these in avoiding platelet transfusions prior to surgery, the additional long-term gain in quality-adjusted life-years was very small. No thrombopoietin receptor agonist was clearly cheaper than both lusutrombopag and avatrombopag, as the cost savings from avoiding platelet transfusions were more than offset by the drug cost. The probabilistic sensitivity analysis showed that, for all thresholds below £100,000, no thrombopoietin receptor agonist had 100% probability of being cost-effective. LIMITATIONS: Some of the rescue therapy data for lusutrombopag were not available. There were inconsistencies in the avatrombopag data. From the cost-effectiveness point of view, there were several additional important gaps in the evidence required, including the lack of a price for avatrombopag. CONCLUSIONS: Avatrombopag and lusutrombopag were superior to no thrombopoietin receptor agonist in avoiding both platelet transfusion and rescue therapy, but they were not cost-effective given the lack of benefit and increase in cost. FUTURE WORK: A head-to-head trial is warranted. STUDY REGISTRATION: This study is registered as PROSPERO CRD42019125311. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 51. See the NIHR Journals Library website for further project information.

Thrombocytopenia, which is a reduction in platelet numbers in the blood, is a common complication of chronic liver disease. It increases the risk of bleeding during procedures including liver biopsy and transplantation. It can delay or prevent procedures, leading to illness and death. Established treatment largely involves platelet transfusion before the procedure or as rescue therapy for bleeding. This report aims to systematically review the clinical effectiveness and estimate the cost-effectiveness of the first two recently licensed treatments, thrombopoietin receptor agonists avatrombopag (Doptelet^®; Dova Pharmaceuticals, Durham, NC, USA) (60 mg if platelet count is < 40,000/µl and 40 mg if platelet count is 40,000­< 50,000/µl) and lusutrombopag (Mulpleta^®; Shionogi Inc., London, UK) (3 mg if platelet count is < 50,000/µl), compared with established treatment. From a comprehensive search, six studies were included. Clinical effectiveness analysis showed that avatrombopag and lusutrombopag were superior to no thrombopoietin receptor agonist in avoiding both platelet transfusion and rescue therapy. Only avatrombopag seemed superior to no thrombopoietin receptor agonist in reducing rescue therapy alone. Cost-effectiveness analysis found that lusutrombopag and avatrombopag were more expensive than no thrombopoietin receptor agonist over a lifetime, as the savings from avoiding platelet transfusions were exceeded by the drug cost, and without long-term health benefits. The probabilistic sensitivity analysis, which examined the effect of uncertainty, showed that no thrombopoietin receptor agonist had 100% probability of being cost-effective. Uncertainty about the price of avatrombopag and the content and costs of platelet transfusions and the potential under-reporting of use to estimate platelet transfusion-specific mortality had the greatest impact on results. If the price of avatrombopag was (confidential information has been removed) below the price of lusutrombopag, avatrombopag would become cost saving in the 40,000­< 50,000/µl subgroup. However, although in some scenarios avatrombopag costs could decrease in the 40,000­< 50,000/µl subgroup to around 10% more than the cost of no thrombopoietin receptor agonist, there would be negligible health benefits and the incremental cost-effectiveness ratios would remain very high, meaning that lusutrombopag and avatrombopag would still not be considered cost-effective.

Treatment patterns and costs among patients with OAB treated with combination oral therapy, sacral nerve stimulation, percutaneous tibial nerve stimulation, or onabotulinumtoxinA in the United States.

INTRODUCTION: Treatment patterns and costs were characterized among patients with overactive bladder (OAB) receiving later-line target therapies (combination mirabegron/antimuscarinic, sacral nerve stimulation [SNS], percutaneous tibial nerve stimulation [PTNS], or onabotulinumtoxinA). METHODS: In a retrospective cohort study using 2013 to 2017 MarketScan databases, two partially overlapping cohorts of adults with OAB ("IPT cohort": patients with incident OAB pharmacotherapy use; "ITT cohort," incident target therapy) with continuous enrollment were identified; first use was index. Demographic characteristics, treatment patterns and costs over the 24-month follow-up period were summarized. Crude mean (standard deviation [SD]) OAB-specific (assessed by OAB diagnostic code or pharmaceutical dispensation record) costs were estimated according to target therapy. RESULTS: The IPT cohort comprised 54 066 individuals (mean [SD] age 58.5 [15.0] years; 76% female), the ITT cohort, 1662 individuals (mean [SD] age 62.8 [14.9] years; 83% female). Seventeen percent of the IPT cohort were treated with subsequent line(s) of therapy after index therapy; among those, 73% received antimuscarinics, 23% mirabegron, and 1.4% a target therapy. For the ITT cohort, 32% were initially treated with SNS, 27% with onabotulinumtoxinA, 26% with combination mirabegron/antimuscarinic, and 15% with PTNS. Subsequently, one-third of this cohort received additional therapies. Mean (SD) costs were lowest among patients receiving index therapy PTNS ($6959 [$7533]) and highest for SNS ($29 702 [$26 802]). CONCLUSIONS: Costs for SNS over 24 months are substantially higher than other treatments. A treatment patterns analysis indicates that oral therapies predominate; first-line combination therapy is common in the ITT cohort and uptake of oral therapy after procedural options is substantial.

Análisis de costes y consecuencias relacionados con la persistencia del tratamiento con Mirabegrón y los fármacos antimuscarínicos y su impacto sobre la calidad de vida en los pacientes con vejiga hiperactiva en España: resultados de un modelo probabilístico / Analysis of costs and consequences related to the persistence of Mirabegron and antimuscarinic treatments and their impact on quality of life in patients with overactive bladder in Spain: Results of a probabilistic model

OBJETIVO: Evaluar si la menor tasa de abandonos del tratamiento de la vejiga hiperactiva (VH) con mirabegrón podría generar ahorros para el Sistema Nacional de Salud (SNS) y ganancia de años de vida ajustados por calidad (AVACs), en comparación con los fármacos antimuscarínicos (AM) (tolterodina, fesoterodina, oxibutinina, solifenacina). MÉTODOS: Modelo probabilístico (simulación de Monte Carlo de segundo orden) en una cohorte hipotética de 1.000 pacientes con VH y un horizonte temporal de 1 año. Las tasas de abandono/persistencia del tratamiento con mirabegrón y AM se obtuvieron de un estudio observacional español en 1.798 pacientes. Los costes unitarios (€ 2018) y la pérdida de utilidades ligada al abandono del tratamiento se obtuvieron de precios públicos españoles y de la literatura, respectivamente. RESULTADOS: En cada paciente tratado con mirabegrón se duplica la tasa de persistencia en comparación con los AM, ganándose anualmente 0,0151 ±0,0007 AVACs, frente a AM. Con mirabegrón se generaría un ahorro anual por paciente de 80,74 ± 4,61 € en comparación con los AM, con una probabilidad de ahorro del 100%. La sustitución hipotética de los AM por mirabegrón, generaría en el plazo de 1 año un ahorro para el SNS de 6,6 millones de euros (IC 95%3,9-10,1 millones de euros) y se ganarían 1.238 AVAC (IC95% 731; 1.885 AVAC). CONCLUSIONES: El modelo probabilístico muestra una mayor persistencia en pacientes tratados con mirabegrón en comparación con los AM, generando un impacto positivo sobre la calidad de vida de los pacientes así como ahorros para el SNS

OBJECTIVE: To evaluate whether the lower dropout rate of the treatment of overactive bladder (OAB) with mirabegron could generate cost savings to the National Health System (NHS) and lead to quality-adjusted life years (QALYs) gains, compared to the most commonly prescribed antimuscarinics (AM) in Spain (tolterodine, fesoterodine, oxybutynin, solifenacin). METHODS: A probabilistic model (second order Monte Carlo simulation) in a hypothetical cohort of 1,000 patients with OAB and a time horizon of 1 year was carried out. Discontinuation and persistence rates for both mirabegron and AM were obtained from a Spanish observational study in 1798 patients. Unit costs (€ 2018) and utility loss associated with treatment discontinuation were obtained from Spanish public prices and literature, respectively. RESULTS: Persistence rates in patients treated with mirabegron were twice as high compared to AM, leading to a QALY gain of 0.0151 ± 0.0007 per year. Treatment with mirabegron could generate savings of 80.74 ± 4.61 € per patient per year compared to AM, assuming 100% probability of saving. The hypothetical substitution of AM treatment for mirabegron could potentially generate savings of 6.6 million euros (95% CI 3.9-10.1 million euros) to the NHS and 1,238 QALYs gains (CI 95% 731; 1,885 QALYs) within a period of 1 year. CONCLUSIONS: The probabilistic model presented showed a greater persistence in patients treated with mirabegron compared to AM, leading to a positive impact in patients quality of life, as well cost savings to the NHS in Spain

Health Care Cost in Patients With Schizophrenia Treated With Brexpiprazole Versus Other Oral Atypical Antipsychotic Therapy.

PURPOSE: Brexpiprazole is an oral atypical antipsychotic (OAA) for the treatment of schizophrenia (SCZ). This study compared all-cause and psychiatric inpatient hospitalization and medical costs in adult patients with SCZ newly treated with brexpiprazole versus other US Food and Drug Administration-approved OAAs in a real-world setting. METHODS: This retrospective cohort study analyzed data from: (1) the IBM MarketScan Commercial and Medicare Supplemental databases, and the MarketScan Multi-State Medicaid database; and (2) the de-identified Optum Clinformatics Datamart. Adult patients were identified if they had SCZ and initiated either brexpiprazole or another OAA during the study identification period (July 1, 2015, to September 30, 2016, for MarketScan Commercial and Medicare Supplemental and for Optum; July 1, 2015, to June 30, 2016, for MarketScan Multi-State Medicaid) and had ≥12 months of continuous enrollment before (baseline) and after (follow-up) the first treatment date. Linear regression analyses were performed to test associations between treatment groups (brexpiprazole vs another OAA) and costs (total and medical); negative binomial regression models were used to estimate number of hospitalizations per year, adjusting for baseline characteristics and medication adherence to index treatment during the 12-month follow-up. FINDINGS: The final study sample consisted of 6254 patients with SCZ: 176 initiated brexpiprazole; 391, ziprasidone; 453, paliperidone; 523, lurasidone; 786, aripiprazole; 1234, quetiapine; 1264, olanzapine; and 1427, risperidone. Controlling for baseline characteristics and medication adherence, the adjusted number of hospitalizations (both all-cause and psychiatric), all-cause total costs, and all-cause medical costs did not differ across groups. Brexpiprazole users had the lowest mean psychiatric costs among all OAA users ($12,013; 95% bootstrap CI, 7488-16,538). Compared with brexpiprazole users, paliperidone (incidence rate ratio [95% CI], 1.52 [1.05-2.19]; P = 0.027) and quetiapine (incidence rate ratio [95% CI], 1.47 [1.04-2.07]; P = 0.029) users had more psychiatric hospitalizations per year. Paliperidone had higher psychiatric costs than brexpiprazole (total, $32,066 [95% bootstrap CI, 28,779-35,353] vs $23,851 [18,907-28,795]; medical, $19,343 [16,294-22,392] vs $12,013 [7488-16,538]). Psychiatric medical costs were also $6744 higher in olanzapine users (95% bootstrap CI, 1694-11,795; P = 0.009) than in brexpiprazole users. IMPLICATIONS: Patients with SCZ treated with brexpiprazole had fewer psychiatric hospitalizations and lower psychiatric costs than those treated with paliperidone. Differences in the number of all-cause hospitalizations and medical costs among treatments were not statistically significant. Although treatment decisions are driven by a number of factors (eg, clinical circumstances and drug costs), choice of OAA may affect health care costs.

Total costs of treating venous thromboembolism: implication of different cost perspectives in a Danish setting.

Aim: Optimal use of scarce resources is a focus in the healthcare sector, as resources devoted to health care are limited. Costs and health economic analyses can help guide decision-making concerning treatments. One important factor is the choice of cost perspective that can range from a focus on narrow drug budget costs to broader economic perspectives. In the case of treatment with oral anticoagulants in patients with venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, the aim of this cost analysis was to illustrate the differences in costs when applying different cost perspectives.Methods: In a cost analysis, pairwise comparisons of average costs of 6 months standard treatment with either a low molecular weight heparin parenteral anticoagulant (LMWH) and a Vitamin K Antagonist (VKA) versus one of the non-vitamin K oral anticoagulants [NOACs; dabigatran etexilate, rivaroxaban, apixaban, and edoxaban) used in daily clinical practice in Denmark for VTE patients were carried out. Each analysis included the results from five different cost analyses with increasingly broader cost perspectives going from the narrowest "drug cost only" perspective to the broadest "societal" perspective.Results: Focusing on "drug costs only", LMWH/VKA was associated with the lowest costs compared to all NOACs. However, including the economic impact of preventing recurrent VTE and limit bleedings, apixaban and rivaroxaban resulted in slightly lower health care costs than LMWH/VKA. When applying the "societal perspective", the total costs saved with apixaban and rivaroxaban compared to LMWH/VKA further increased, with apixaban having the lowest total costs.Conclusions: The present study's case of oral anticoagulants in VTE treatment illustrated the importance of the cost perspective in the choice of therapy. If decision-making were based on drug costs only, instead of applying a health care sector or societal cost perspective, suboptimal decisions may be likely.

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.

Cost-effectiveness of edoxaban versus dalteparin for the treatment of cancer-associated thrombosis.

Malignancy is a well-established risk factor for venous thromboembolism and while low-molecular-weight heparin therapy has been standard of care for cancer-associated thrombosis for many years, many patients find injection therapy burdensome. The direct oral anticoagulant edoxaban has been shown to be noninferior to dalteparin for the treatment of cancer-associated thrombosis. In a Markov simulation model, edoxaban with 6-month time horizon and a United States societal perspective with 2017 US dollars, edoxaban was the preferred strategy in the general cancer population (6-month cost $6061 with 0.34 quality adjusted life years) and in a subgroup of patients with gastrointestinal malignancy (6-month cost $7227 with 0.34 quality adjusted life years). The incremental cost effectiveness ratio of dalteparin compared to edoxaban was $1,873,535 in the general oncology population and $694,058 in the gastrointestinal malignancy population.

Would the Use of Edoxaban Be Cost-effective for the Prevention of Stroke and Systemic Embolism in Patients With Nonvalvular Atrial Fibrillation in Spain?

INTRODUCTION AND OBJECTIVES: To assess the cost-effectiveness of edoxaban vs acenocoumarol in the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF) in Spain. METHODS: Markov model, adapted to the Spanish setting from the perspective of the National Health System, stimulating the progression of a hypothetical cohort of patients with NVAF throughout their lifetime, with different health states: stroke, haemorrhage, and other cardiovascular complications. Efficacy and safety data were obtained from the available clinical evidence (mainly from the phase III ENGAGE AF-TIMI 48 study). The costs of managing NVAF and its complications were obtained from Spanish sources. RESULTS: Edoxaban use led to 0.34 additional quality-adjusted life years (QALY) compared with acenocoumarol. The incremental cost with edoxaban was 3916€, mainly because of higher pharmacological costs, which were partially offset by lower costs of treatment monitoring and managing NVAF events and complications. The cost per QALY was 11 518€, within the thresholds commonly considered cost-effective in Spain (25 000-30 000 €/QALY). The robustness of the results was confirmed by various sensitivity analyses. CONCLUSIONS: Edoxaban is a cost-effective alternative to acenocoumarol in the prevention of stroke and systemic embolism in patients with NVAF in Spain.

Cost-effectiveness of overactive bladder treatments: from the US payer perspective.

AIM: To assess the cost-effectiveness of onabotulinumtoxinA (onabotA), implantable sacral nerve stimulation devices, percutaneous tibial nerve stimulation, anticholinergic medications and mirabegron compared with best supportive care (BSC) for management of refractory overactive bladder (OAB). METHODS: A Markov model was developed to compare the cost-effectiveness of treatment options with BSC over a 10-year time horizon. Resource utilization, discontinuation rates and costs were derived from unpublished and published sources. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios were reported. RESULTS: Treatment with onabotA 100U produced the largest gain in QALYs (7.179) and lowest estimated incremental cost-effectiveness ratio ($32,680/QALY) of all assessed treatments compared with BSC. CONCLUSION: Compared with BSC, onabotA 100U was the most cost-effective treatment option for patients with refractory OAB.

Anticoagulation Therapy for Atrial Fibrillation in Patients With Alzheimer's Disease.

Background and Purpose- Direct oral anticoagulants (DOACs) are safer, at least equally efficacious, and cost-effective compared to warfarin for stroke prevention in atrial fibrillation (AF) but they remain underused, particularly in demented patients. We estimated the cost-effectiveness of DOACs compared with warfarin in patients with AF and Alzheimer's disease (AD). Methods- We constructed a microsimulation model to estimate the lifetime costs, quality-adjusted life-years (QALYs), and cost-effectiveness of anticoagulation therapy (adjusted-dose warfarin and various DOACs) in 70-year-old patients with AF and AD from a US societal perspective. We stratified patient cohorts based on stage of AD and care setting. Model parameters were estimated from secondary sources. Health benefits were measured in the number of acute health events, life-years, and QALYs gained. We classified alternatives as cost-effective using a willingness-to-pay threshold of $100 000 per QALY gained. Results- For patients with AF and AD, compared with warfarin, DOACs increase costs but also increase QALYs by reducing the risk of stroke. For mild-AD patients living in the community, edoxaban increased lifetime costs by $6603 and increased QALYs by 0.076 compared to warfarin, yielding an incremental cost-effectiveness ratio of $86 882/QALY gained. Even though DOACs increased QALYs compared with warfarin for all patient groups (ranging from 0.019 to 0.085 additional QALYs), no DOAC treatment alternative had an incremental cost-effectiveness ratio <$150 000/QALY gained for patients with moderate to severe AD. For patients living in a long-term care facility with mild AD, the DOAC with the lowest incremental cost-effectiveness ratio (rivaroxaban) costs $150 169 per QALY gained; for patients with more severe AD, the incremental cost-effectiveness ratios were higher. Conclusions- For patients with AF and mild AD living in the community, edoxaban is cost-effective compared with warfarin. Even though patients with moderate and severe AD living in the community and patients with any stage of AD living in a long-term care setting may obtain positive clinical benefits from anticoagulation treatment, DOACs are not cost-effective compared with warfarin for these populations. Compared to aspirin, no oral anticoagulation (warfarin or any DOAC) is cost effective in patients with AF and AD.

Mirabegron or tolterodine for the treatment of overactive bladder in Japan: Which drug is more cost-effective as the first-line treatment?

OBJECTIVES: To assess the cost-effectiveness of mirabegron 50 mg relative to tolterodine extended release 4 mg for the treatment of overactive bladder if used as the first-line treatment in Japan. METHODS: A Markov model was developed to simulate the cost-effectiveness of the mirabegron first-line treatment (and tolterodine second-line) versus tolterodine first-line treatment (and mirabegron second-line) taken for 5 years from the randomized European-Australian study (SCORPIO trial) and single technology appraisal assessment report by the National Institute for Health and Care Excellence. The incremental cost-effectiveness ratio was calculated with utility value by quality-adjusted life year with cost using the medical fee and the drug price tariff in 2016. For the study of transition of treatment status, our analytical model was established. The transition probabilities of severity states were calculated based on the probabilities for the mean numbers of incontinence episodes/day and micturition episodes/day in mirabegron-treated and tolterodine-treated patients in the single technology appraisal assessment report. RESULTS: The 5-year expected effect per patient was 3.860 quality-adjusted life years for first-line mirabegron and 3.839 quality-adjusted life years for first-line tolterodine. The 5-year expected cost per patient was ¥526 191 for first-line mirabegron, and ¥472 390 for first-line tolterodine. The incremental cost-effectiveness ratio was ¥2 565 927/quality-adjusted life year. This value was below the willingness-to-pay threshold of ¥5 million/quality-adjusted life year. In more severe states, the incremental cost-effectiveness ratio exceeded ¥5 million. CONCLUSIONS: First-line mirabegron appears to be more cost-effective than first-line tolterodine. In patients with severe symptoms, first-line mirabegron is not economically preferable.

Edoxaban therapy increases treatment satisfaction and reduces utilization of healthcare resources: an analysis from the EdoxabaN vs. warfarin in subjectS UndeRgoing cardiovErsion of atrial fibrillation (ENSURE-AF) study.

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.

Comparing the Cost Effectiveness of Non-vitamin K Antagonist Oral Anticoagulants with Well-Managed Warfarin for Stroke Prevention in Atrial Fibrillation Patients at High Risk of Bleeding.

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%.

The impact of persistence with mirabegron usage vs switching to onabotulinumtoxinA on healthcare costs and resource utilization in patients with overactive bladder in the United States.

AIMS: To compare healthcare costs and resource utilization in patients with overactive bladder (OAB) in the US who switch from mirabegron to onabotulinumtoxinA (onabotA) with those who persist on mirabegron. MATERIALS AND METHODS: A retrospective observational claims analysis of the OptumHealth Administrative Claims database conducted between April 1, 2012 and September 30, 2015 used medical and pharmacy claims to identify patients with at least one OAB diagnosis who switched from mirabegron to onabotA (onabotA group) or persisted on mirabegron for at least 180 days (mirabegron persisters). Propensity score weighting was used to balance baseline characteristics that were associated with increased healthcare expenditures across treatment groups. Multivariate analyses assessed the impact of switching and persistence on all-cause and OAB-related healthcare costs and resource utilization in the year following each patient's index date. RESULTS: In total, 449 patients were included in this study: 54 patients were included in the onabotA group, and 395 patients were included in the mirabegron persister group. Compared with the mirabegron persister patients, the onabotA patients observed significantly higher OAB-related total costs ($5,504 vs $1,772, p < .001), OAB-related medical costs ($5,033 vs $351, p < .001), sacral neuromodulation costs ($865 vs $60, p = .017), and outpatient costs ($17,385 vs $9,035, p = .009), and more OAB-related medical visits (6.0 vs 1.9, p < .001). OnabotA patients had lower OAB-related prescription costs ($470 vs $1,421, p < .001) and fewer OAB-related pharmacy claims (1.6 vs 5.0, p <.001). There were no significant differences in all-cause total medical or prescription costs. LIMITATIONS: This study was a retrospective analysis using claims data that only included patients with commercial health coverage or Medicare supplemental coverage. Accuracy of the diagnosis codes and the generalizability of the results to other OAB populations are limited. The study was not designed to determine the impact of OAB treatments on the economic outcomes examined. CONCLUSIONS: OAB patients who persisted on mirabegron treatment for at least 180 days had lower OAB-related healthcare costs and resource utilization compared with those who switched to onabotA.

[Mirabegron, a breakthrough in overactive bladder syndrome?] / Mirabegrón ¿un avance en el síndrome de vejiga hiperactiva?

OBJECTIVE: Overactive bladder syndrome is a condition with high prevalence, which has a negative impact on patients' quality of life. A drug with a novel mechanism of action has been recently approved: mirabegron. The objective of this study is to review the scientific evidence available on mirabegron, with the aim to analyze its efficacy, safety and cost, and thus estimate its role within current pharmacotherapy. Methods: The effectiveness and safety of mirabegron were analyzed through an evaluation of scientific evidence. The cost of different pharmacological alternatives was calculated based on their Defined Daily Dose (DDD) and their manufacturer's sale price. Results: The use of mirabegron in the treatment of overactive bladder syndrome is supported by three randomized clinical trials, controlled with placebo, at 12 weeks. All three share the same primary efficacy variables (number of incontinence episodes per 24 hours and number of micturitions per 24 hours). Long-term efficacy data are based on a 12-month study, where efficacy outcomes were measured as secondary variables. In all studies, mirabegron showed a significant but modest effect. Some of the most frequently detected adverse effects were: hypertension, increase of glucose in blood, headache, urinary tract infections, constipation and tachycardia. Special attention must be paid to cardiovascular events. Conclusions: The clinical efficacy of mirabegron is very modest and comparable to that achieved with the other drugs approved for this indication. Moreover, it is more expensive than other therapeutic options. Cardiac risks and urinary infections only allow to consider it as an alternative option to anticholinergic drugs, when these are contraindicated, show no clinical efficacy, or cause unacceptable adverse effects.

Objetivo: El síndrome de vejiga hiperactiva es una patología con elevada prevalencia y que tiene un impacto negativo sobre la calidad de vida de los pacientes. Recientemente se ha aprobado un fármaco con un novedoso mecanismo de acción: el mirabegrón. El objetivo de este estudio es revisar la evidencia científica disponible sobre el mirabegrón, con el fin de analizar su eficacia, seguridad y coste, y así estimar su papel en la farmacoterapia actual.Metodología: La eficacia y seguridad del mirabegrón se analizó mediante una evaluación de la evidencia científica. El coste de las diferentes alternativas farmacológicas se calculó en base a sus dosis diarias definidas (DDD) y el precio de venta del laboratorio. Resultados: Tres ensayos clínicos aleatorizados, controlados con placebo, de 12 semanas de duración, apoyan el uso del mirabegrón en el tratamiento del síndrome de vejiga hiperactiva. Los tres comparten las mismas variables principales de eficacia (número de episodios de incontinencia/24 h y número de micciones/24 h). Los datos de eficacia a largo plazo se basan en un estudio de seguridad de 12 meses de duración en el que los resultados de eficacia se medían como variables secundarias. En todos los estudios, el mirabegrón mostró un efecto significativo pero modesto. Entre los efectos adversos más frecuentes se detectaron hipertensión, aumento de glucosa en sangre, dolor de cabeza, infecciones del tracto urinario, estreñimiento y taquicardia. Se debe prestar especial atención a los eventos cardiovasculares. Conclusiones: La eficacia clínica del mirabegrón es muy modesta y comparable a la conseguida con el resto de fármacos aprobados para esta indicación. Además, presenta un mayor coste que otras alternativas terapéuticas. Los riesgos cardiacos e infecciones urinarias solo hacen posible considerarlo como  una alternativa a los anticolinérgicos cuando estos estén contraindicados, sean clínicamente ineficaces o sus efectos adversos sean inaceptables.