The cost of warfarin treatment for stroke prevention in patients with non-valvular atrial fibrillation in Mexico from a collective perspective

Aims: To describe the collective costs of vitamin K antagonist (VKA) treatment for stroke prevention in non-valvular atrial fibrillation (NVAF). VKA drug costs are relatively low, but they necessitate frequent international normalized ratio (INR) monitoring. There are currently minimal data describing the economic impact of this in Mexico.

Materials and methods: Cardiologists provided data on their NVAF patients (n?=?400) to quantify direct medical costs (INR testing, appointments, drug costs). A sub-set of patients (n?=?301) completed a patient questionnaire providing data to calculate direct non-medical costs (travel and other expenses for attendance at VKA-associated appointments) and indirect costs (opportunity cost and reduced work productivity associated with VKA treatment).

Results: Estimated annual direct medical costs totaled $753.6 per patient. Annual direct non-medical and indirect costs were USD$149.8 and $132.1, respectively.

Limitations: Recruited patients were those who consulted with a cardiologist during the study period and selected due to inclusion criteria. All had received uninterrupted treatment for 12–24 months. Consequently, the results are not fully generalizable to all VKA treated NVAF patients.

Conclusions: The true cost of VKA treatment cannot be appreciated by a consideration of drug costs alone. Ongoing monitoring appointments incur additional expenses for both patients and the healthcare system.     

Number needed to treat based on real-world evidence for non-vitamin K antagonist oral anticoagulants versus vitamin K antagonist oral anticoagulants in stroke prevention in patients with non-valvular atrial fibrillation

Aims: Non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) are used to prevent stroke in patients with atrial fibrillation (AF). This paper aimed to evaluate the clinical efficacy and safety of NOACs when compared to VKAs by calculating the number needed to treat (NNT) at 2 years using incidence rates and hazard ratios (HRs) derived from a meta-analysis of studies conducted in real-world settings.

Materials and methods: HRs were sourced from a published systematic literature review and a meta-analysis of real-world evidence on the use of NOACs vs VKAs. Rivaroxaban, dabigatran, and apixaban vs VKAs were investigated. The efficacy outcomes included: a composite of ischaemic stroke and systemic embolism (IS/SE), ischaemic stroke (IS), and all-cause mortality. The safety analysis assessed major bleeding and intracranial haemorrhage (ICH).

Results: Superiority of NOACs vs VKAs was observed in 10/15 comparisons. Treating patients with rivaroxaban and dabigatran was associated with a reduced risk of IS and all-cause mortality compared to VKAs, with one death prevented every 22 and 32 patients, respectively, and one IS prevented every 206 and 166 patients, respectively. Rivaroxaban was significantly associated with a reduced risk of IS/SE compared to VKA (NNT: 107). No significant differences were observed between apixaban and VKAs. Dabigatran and apixaban were associated with a reduced risk of major bleeding compared to VKA (NNT: 59 and 38, respectively). No significant difference was observed between rivaroxaban and VKAs regarding major bleeding. Rivaroxaban, dabigatran, and apixaban were significantly associated with a reduced risk of ICH (NNT: 205, 115, and 108, respectively).

Limitations: Heterogeneity in definitions of major bleeding across studies.

Conclusions: The NNT calculation, when approached and interpreted properly, is a practical measure of the effectiveness of a treatment. The calculation based on HRs showed that NOACs are safe and effective alternatives to VKAs in real life.     

The cost-effectiveness and monetary benefits of dabigatran in the prevention of arterial thromboembolism for patients with non-valvular atrial fibrillation in the Netherlands

Background: Atrial fibrillation (AF) causes a significant health and economic burden to the Dutch society. Dabigatran was proven to have at least similar efficacy and a similar or better safety profile when compared to vitamin K antagonists (VKAs) in preventing arterial thromboembolism in patients with AF.

Objective: To evaluate the cost-effectiveness and monetary benefit of dabigatran vs VKAs in Dutch patients with non-valvular AF. Value-based pricing considerations and corresponding negotiations on dabigatran will be explicitly considered.

Methods: The base case economic analysis was conducted from the societal perspective. Health effects and costs were analysed using a Markov model. The main model inputs were derived from the RE-LY trial and Dutch observational data. Univariate, probabilistic sensitivity, and various scenario analyses were performed.

Results: Dabigatran was cost saving compared to VKAs. A total of 4,552 QALYs were gained, and €13,892,288 was saved in a cohort of 10,000?AF patients. The economic value of dabigatran was strongly related to the costs of VKA control that are averted. Notably, dabigatran was cost saving compared to VKAs if annual costs of VKA control exceeded €159 per person, or dabigatran costs were below €2.81 per day.

Conclusion: Dabigatran was cost saving compared to VKAs for the prevention of atrial thromboembolism in patients with non-valvular AF in the Netherlands. This result appeared robust in the sensitivity analysis. Furthermore, volume based reduction of the price in the Netherlands will further increase the monetary benefits of dabigatran.     

Clinical and economic impact of rivaroxaban on the burden of atrial fibrillation: The case study of Japan

Objectives: Atrial fibrillation (AF) affects an estimated 1.5 million individuals in Japan, increasing their stroke risk and imposing considerable costs on the Japanese healthcare system. To reduce stroke incidence, guidelines recommend using anticoagulants in moderate-to-high risk non-valvular AF (NVAF) patients; however, many patients receive no treatment, aspirin only, or remain poorly-controlled on vitamin K antagonists (VKAs) due to high VKA discontinuation rates and non-adherence to guidelines. A prevalence-based Markov model was developed to estimate the clinical and budgetary impact of treating these patients with Xarelto^TM (rivaroxaban, Bayer AG) in Japan.

Methods: Population, baseline risk of events, and associated management costs were estimated using data from Japanese publications where available. Treatment efficacy and safety were derived from published data and the J-ROCKET AF trial. Drug and physician visit costs were based on data from the Ministry of Health, Labor, and Welfare, the J-ROCKET AF trial, and Japanese clinical guidelines.

Results: This model demonstrates that increased use of rivaroxaban in inadequately-managed NVAF patients could avoid 456 081 non-fatal ischemic strokes (IS) and 76 975 cardiovascular deaths over 10 years in Japan. This clinical benefit offsets the increased incidence of myocardial infarctions and anticoagulant-related bleeding. Decreased event costs could lead to a ¥188.4 billion decrease in net spending over the analysis time horizon.

Conclusions: Introducing rivaroxaban may decrease the burden of NVAF in Japanese society. From a clinical perspective, the reduction in IS and embolic events outweighs the increased risk of anticoagulant-related bleeding; from an economic perspective, reduced event costs offset drug and physician visit costs, resulting in cost savings.     

Cost-effectiveness of dabigatran etexilate in the prevention of stroke and systemic embolism in patients with atrial fibrillation in Belgium

Abstract

Objective:

To assess the cost-effectiveness of dabigatran etexilate (‘dabigatran’) vs vitamin K antagonists (VKAs) in the Belgian healthcare setting for the prevention of stroke and systemic embolism (SE) in patients with non-valvular atrial fibrillation (AF).

Research design and methods:

A Markov model was used to calculate the cost-effectiveness of dabigatran vs VKAs in Belgium, whereby warfarin was considered representative for the VKA class. Efficacy and safety data were taken from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial and a network meta-analysis. Local resource use and unit costs were included in the model. Effectiveness was expressed in Quality Adjusted Life-Years (QALYs). The model outcomes were total costs, total QALYs, incremental costs, incremental QALYs and the incremental cost-effectiveness ratio (ICER). The level of International Normalized Ratio (INR) control and the use of other antithrombotic therapies observed in Belgian clinical practice were reflected in two scenario analyses.

Results:

In the base case analysis, total costs per patient were €13,333 for dabigatran and €12,454 for warfarin. Total QALYs per patient were 9.51 for dabigatran and 9.19 for warfarin. The corresponding ICER was €2807/QALY. The ICER of dabigatran was €970/QALY vs warfarin with real-world INR control and €5296/QALY vs a mix of warfarin, aspirin, and no treatment. Results were shown to be robust in one-way and probabilistic sensitivity analyses.

Limitations:

The analysis does not include long-term costs for clinical events, as these data were not available for Belgium. As in any economic model based on data from a randomized clinical trial, several assumptions had to be made when extrapolating results to routine clinical practice in Belgium.

Conclusion:

This analysis suggests that dabigatran, a novel oral anticoagulant, is a cost-effective treatment for the prevention of stroke and SE in patients with non-valvular AF in the Belgian healthcare setting.     

Major bleeding risk and healthcare economic outcomes of non-valvular atrial fibrillation patients newly-initiated with oral anticoagulant therapy in the real-world setting

Aims: This study compared the risk for major bleeding (MB) and healthcare economic outcomes of patients with non-valvular atrial fibrillation (NVAF) after initiating treatment with apixaban vs rivaroxaban, dabigatran, or warfarin.

Methods: NVAF patients who initiated apixaban, rivaroxaban, dabigatran, or warfarin were identified from the IMS Pharmetrics Plus database (January 1, 2013–September 30, 2015). Propensity score matching (PSM) was used to balance differences in patient characteristics between study cohorts: patients treated with apixaban vs rivaroxaban, apixaban vs dabigatran, and apixaban vs warfarin. Risk of hospitalization and healthcare costs (all-cause and MB-related) were compared between matched cohorts during the follow-up.

Results: During the follow-up, risks for all-cause (hazard ratio [HR]?=?1.44, 95% confidence interval [CI]?=?1.2–1.7) and MB-related (HR?=?1.57, 95% CI?=?1.0–2.4) hospitalizations were significantly greater for patients treated with rivaroxaban vs apixaban. Adjusted total all-cause healthcare costs were significantly lower for patients treated with apixaban vs rivaroxaban ($3,950 vs $4,333 per patient per month [PPPM], p?=?.002) and MB-related medical costs were not statistically significantly different ($100 vs $233 PPPM, p?=?.096). Risk for all-cause hospitalization (HR?=?1.98, 95% CI?=?1.6–2.4) was significantly greater for patients treated with dabigatran vs apixaban, although total all-cause healthcare costs were not statistically different. Risks for all-cause (HR?=?2.22, 95% CI?=?1.9–2.5) and MB-related (HR?=?2.05, 95% CI?=?1.4–3.0) hospitalizations were significantly greater for patients treated with warfarin vs apixaban. Total all-cause healthcare costs ($3,919 vs $4,177 PPPM, p?=?.025) and MB-related medical costs ($96 vs $212 PPPM, p?=?.026) were significantly lower for patients treated with apixaban vs warfarin.

Limitations: This retrospective database analysis does not establish causation.

Conclusions: In the real-world setting, compared with rivaroxaban and warfarin, apixaban is associated with reduced risk of hospitalization and lower healthcare costs. Compared with dabigatran, apixaban is associated with lower risk of hospitalizations.     

Out-of-range international normalized ratio values and healthcare cost among new warfarin patients with non-valvular atrial fibrillation

Abstract

Background:

Patients with out-of-range international normalized ratio (INR) values <2.0 and >3.0 have been associated with increased risk of thromboembolic and bleeding events. INR monitoring is costly, because of associated physician and nurse time, laboratory resource use, and dose adjustments.     

Stroke prevention in patients with atrial fibrillation in France: comparative cost-effectiveness of new oral anticoagulants (apixaban,dabigatran, and rivaroxaban), warfarin,and aspirin

Objectives:

To conduct an economic evaluation of the currently prescribed treatments for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) including warfarin, aspirin, and novel oral anticoagulants (NOACs) from a French payer perspective.

Methods:

A previously published Markov model was adapted in accordance to the new French guidelines of the Commission for Economic Evaluation and Public Health (CEESP), to adopt the recommended efficiency frontier approach. A cohort of patients with NVAF eligible for stroke preventive treatment was simulated over lifetime. Clinical events modeled included strokes, systemic embolism, intracranial hemorrhage, other major bleeds, clinically relevant non-major bleeds, and myocardial infarction. Efficacy and bleeding data for warfarin, apixaban, and aspirin were obtained from ARISTOTLE and AVERROES trials, whilst efficacy data for other NOACs were from published indirect comparisons. Acute medical costs were obtained from a dedicated analysis of the French national hospitalization database (PMSI). Long-term medical costs and utility data were derived from the literature. Univariate and probabilistic sensitivity analyses were performed to assess the robustness of the model projections.

Results:

Warfarin and apixaban were the two optimal treatment choices, as the other five treatment strategies including aspirin, dabigatran 110?mg, dabigatran in sequential dosages, dabigatran 150?mg, and rivaroxaban were strictly dominated on the efficiency frontier. Further, apixaban was a cost-effective alternative vs warfarin with an incremental cost of €2314 and an incremental quality-adjusted life year (QALY) of 0.189, corresponding to an incremental cost-effectiveness ratio (ICER) of €12,227/QALY.

Conclusions:

Apixaban may be the most economically efficient alternative to warfarin in NVAF patients eligible for stroke prevention in France. All other strategies were dominated, yielding apixaban as a less costly yet more effective treatment alternative. As formally requested by the CEESP, these results need to be verified in a French clinical setting using stroke reduction and bleeding safety observed in real-life patient cohorts using these anticoagulants.     

Cost-effectiveness of the convergent procedure and catheter ablation for non-paroxysmal atrial fibrillation

Objective:

Patients with persistent or longstanding atrial fibrillation have modest success achieving sinus rhythm with catheter ablation or rhythm control medications. Their high risk of stroke, bleed, and heart failure leads to significant morbidity and health care costs. The convergent procedure has been shown to be successful in this population, with 80% of patients in sinus rhythm after 1 year. This study evaluated the cost-effectiveness of the convergent procedure, catheter ablation, and medical management for non-paroxysmal AF patients.

Methods:

A Markov micro-simulation model was used to estimate costs and effectiveness from a payer perspective. Parameter estimates were from the literature. Three patient cohorts were simulated, representing lower, medium, and higher risks of stroke, bleed, heart failure, and hospitalization. Effects were estimated by quality-adjusted life-years (QALYs). Single-variable sensitivity analysis was performed.

Results:

After 5 years, convergent procedure patients averaged 1.10 procedures, with 75% of survivors in sinus rhythm; catheter ablation patients had 1.65 procedures, with 49% in sinus rhythm. Compared to medical management, catheter ablation and the convergent procedure were cost-effective for the lower risk (ICER <$35,000) and medium risk (ICER <$15,000) cohorts. The procedures dominated medical management for the higher risk cohort (lower cost and higher QALYs). The convergent procedure dominated catheter ablation for all risk cohorts. Results were subject to simplifying assumptions and limited by uncertain factors such as long-term maintenance of sinus rhythm after successful procedure and incremental AF-associated event rates for AF patients relative to patients in sinus rhythm. In the absence of clinical trial data, convergent procedure efficacy was estimated with observational evidence. Limitations were addressed with sensitivity analyses and a moderate 5 year time horizon.

Conclusion:

The convergent procedure results in superior maintenance of post-ablation sinus rhythm with fewer repeat ablation procedures compared to catheter ablation, leading to lower cost and higher QALYs after 5 years.     

The cost of warfarin treatment for stroke prevention in patients with non-valvular atrial fibrillation in Russia from a collective perspective

Aims: Vitamin K antagonists (VKAs) are used for stroke prevention in patients with non-valvular atrial fibrillation (NVAF), but necessitate regular monitoring of prothrombin time via international normalized ratio (INR) testing. This study explores the economic burden of VKA therapy for Russian patients with NVAF.

Method: Cardiologists provided clinical characteristics and healthcare resource use data relating to the patient’s first year of treatment. Data were used to quantify direct medical costs (INR testing, consultations, drug costs). The same patients completed a questionnaire providing data on direct non-medical costs (travel/expenses for attendance at VKA appointments) and indirect costs (opportunity cost and reduced work productivity). Mean costs per patient per year are described (US dollars).

Results: Cardiologists (n?=?50) provided data on 400 patients (mean age?=?63, 47% female), and 351 patients (88%) completed the patient questionnaire. Patients had a mean of nine INR tests. Estimated direct medical costs totaled $151.06, and 18.5% of direct medical costs were attributable to drug costs. Estimated annual direct non-medical costs were $22.89 per patient, and indirect costs were $275.59 per patient.

Limitations: Included patients had been treated for 12–24 months, so are not fully representative of the broader treatment population.

Conclusion: Although VKA drugs costs are relatively low, regular INR testing and consultations drive the economic burden for Russian NVAF patients treated with VKA.     

Cost-effectiveness of percutaneous patent foramen ovale closure as secondary stroke prevention

Objective: Compared to medical therapy alone, percutaneous closure of patent foramen ovale (PFO) further reduces risk of recurrent ischemic strokes in carefully selected young to middle-aged patients with a recent cryptogenic ischemic stroke. The objective of this study was to evaluate the cost-effectiveness of this therapy in the context of the United Kingdom (UK) healthcare system.

Methods: A Markov cohort model consisting of four health states (Stable after index stroke, Post-Minor Recurrent Stroke, Post-Moderate Recurrent Stroke, and Death) was developed to simulate the economic outcomes of device-based PFO closure compared to medical therapy. Recurrent stroke event rates were extracted from a randomized clinical trial (RESPECT) with a median of 5.9-year follow-up. Health utilities and costs were obtained from published sources. One-way and probabilistic sensitivity analyses (PSA) were performed to assess robustness. The model was discounted at 3.5% and reported in 2016 Pounds Sterling.

Results: Compared with medical therapy alone and using a willingness-to-pay (WTP) threshold of £20,000, PFO closure reached cost-effectiveness at 4.2 years. Cost-effectiveness ratios (ICERs) at 4, 10, and 20 years were ?20,951, ?6,887, and ?2,158, respectively. PFO closure was cost-effective for 89% of PSA iterations at year 10. Sensitivity analyses showed that the model was robust.

Conclusions: Considering the UK healthcare system perspective, percutaneous PFO closure in cryptogenic ischemic stroke patients is a cost-effective stroke prevention strategy compared to medical therapy alone. Its cost-effectiveness was driven by substantial reduction in recurrent strokes and patients’ improved health-related quality-of-life.     

Comparison of hospital length of stay and hospitalization costs among patients with non-valvular atrial fibrillation treated with apixaban or warfarin: An early view

Objective: To quantify and compare hospital length of stay (LOS) and costs between hospitalized non-valvular atrial fibrillation (NVAF) patients treated with either apixaban or warfarin via a large claims database.

Methods: Adult patients hospitalized with AF were selected from the Premier Perspective Claims Database (01JAN2013-31MARCH2014). Patients with evidence of valvular heart disease, valve replacement procedures, or pregnancy during the index hospitalization were excluded. Patients treated with apixaban or warfarin during hospitalization were identified. Propensity score matching (PSM) was performed to control for baseline imbalances between patients treated with apixaban or warfarin. Primary outcomes were hospital LOS (days), post-medication administration LOS, and index hospitalization costs, and were compared using paired t-tests in the matched sample.

Results: Before PSM, 2894 apixaban and 124,174 warfarin patients were identified. Patients treated with warfarin were older and sicker compared to those treated with apixaban. After applying PSM, a total of 2886 patients were included in each cohort, and baseline characteristics were balanced. The mean (standard deviation [SD] and median) hospital LOS was significantly (p?=?0.002) shorter for patients treated with apixaban for 5.1 days (5.7 and 3) compared to warfarin for 5.5 days (4.8 and 4). The trend appeared consistent in the hospital LOS from point of apixaban or warfarin administration to discharge (4.5 vs 4.7 days, p?=?0.051). Patients administered apixaban incurred significantly lower hospitalization costs compared to those administered warfarin ($11,262 vs $12,883; p?<?0.001).

Conclusions: Among NVAF patients, apixaban treatment was associated with significantly shorter hospital LOS and lower costs when compared to warfarin treatment.     

Psychometric validation of anti-clot treatment scale and treatment satisfaction questionnaire for medication version II in Japanese patients with atrial fibrillation

Aims: The Anti-Clot Treatment Scale (ACTS) and Treatment Satisfaction Questionnaire for Medication version II (TSQM-II) are validated treatment satisfaction patient-reported outcome (PRO) instruments. The ACTS includes two domains: Burdens and Benefits; the TSQM-II includes four: Effectiveness, Side Effects, Convenience, and Global Satisfaction. Japanese-language versions of the ACTS and TSQM-II have been developed and linguistically validated. This study aimed to assess their psychometric properties in Japanese patients with atrial fibrillation (AF).

Materials and methods: ACTS and TSQM-II data from 534 patients with AF were collected in a Japanese post-marketing surveillance study of a direct oral-anticoagulant, rivaroxaban. Four key psychometric properties, in line with best practice guidelines from the US Food and Drug Administration, were examined using traditional psychometric methods: acceptability, scaling assumptions, reliability (i.e. internal consistency reliability, test-retest reliability), and construct validity (i.e. convergent validity and known groups).

Results: ACTS Burdens and Benefits and TSQM-II Effectiveness, Convenience, and Global Satisfaction scales were found to be acceptable (e.g. item-level missing data at baseline <4%), with all scales having good internal consistency (Cronbach’s alpha > 0.80). test-retest reproducibility intraclass correlation coefficients for the ACTS Burdens and Benefits were 0.59 and 0.65, respectively, and between 0.54–0.61 for the TSQM-II scales. Known-groups validity for the ACTS and TSQM-II was supported by differences in scale scores by positive and negative impact (p?<?0.05). Correlations between the ACTS and TSQM-II (convergent validity) were lower than expected (range r?=?0.09–0.48), but in line with the original ACTS development study.

Limitations: Evaluation of test-retest reproducibility was limited by assessment period, which was longer (3 months) than recommended guidelines (usually up to 2 weeks).

Conclusions: Overall, Japanese versions of ACTS and TSQM-II scales satisfied internal consistency reliability and traditional validity criteria. Our study supports the ACTS and TSQM-II as appropriate PRO instruments to measure satisfaction with anticoagulant treatment in Japanese patients with AF.

Trial registration: NCT01598051, clinicaltrials.gov; registered April 20, 2012.     

Comparison of differences in medical costs when new oral anticoagulants are used for the treatment of patients with non-valvular atrial fibrillation and venous thromboembolism vs warfarin or placebo in the US

Abstract

Objective:

Medical costs that may be avoided when any of the four new oral anticoagulants (NOACs), dabigatran, rivaroxaban, apixaban, and edoxaban, are used instead of warfarin for the treatment of non-valvular atrial fibrillation (NVAF) were estimated and compared. Additionally, the overall differences in medical costs were estimated for NVAF and venous thromboembolism (VTE) patient populations combined.     

Cost-effectiveness analysis of rivaroxaban for treatment and secondary prevention of venous thromboembolism in the Netherlands

Background: Until recently, standard treatment of venous thromboembolism (VTE) concerned a combination of short-term low-molecular-weight heparin (LMWH) and long-term vitamin-K antagonist (VKA). Risk of bleeding and the requirement for regular anticoagulation monitoring are, however, limiting their use. Rivaroxaban is a novel oral anticoagulant associated with a significantly lower risk of major bleeds (hazard ratio?=?0.54, 95% confidence interval?=?0.37–0.79) compared to LMWH/VKA therapy, and does not require regular anticoagulation monitoring.

Aims: To evaluate the health economic consequences of treating acute VTE patients with rivaroxaban compared to treatment with LMWH/VKA, viewed from the Dutch societal perspective.

Methods: A life-time Markov model was populated with the findings of the EINSTEIN phase III clinical trial to analyze cost-effectiveness of rivaroxaban therapy in treatment and prevention of VTE from a Dutch societal perspective. Primary model outcomes were total and incremental quality-adjusted life years (QALYs), as well as life expectancy and costs.

Results: Over a patient’s lifetime, rivaroxaban was shown to be dominant, with health gains of 0.047 QALYs and cost savings of €304 compared to LMWH/VKA therapy. Dominance was robustly present in all sensitivity analyses. Major drivers of the differences between the two treatment arms were related to anticoagulation monitoring (medical costs, travel costs, and loss of productivity) and the occurrence of major bleeds.

Conclusion: Rivaroxaban treatment of patients with venous thromboembolism results in health gains and cost savings compared to LMWH/VKA therapy. This conclusion holds for the Dutch setting, both for the societal perspective, as well as the healthcare perspective.     

Rivaroxaban for non-valvular atrial fibrillation and venous thromboembolism in the Netherlands: a real-world data based cost-effectiveness analysis

Background: Non-vitamin K antagonist oral anticoagulants (NOACs) have been included in international guidelines as important alternatives to vitamin K antagonists (VKAs) for the treatment of venous thromboembolism (VTE) and stroke prevention in non-valvular atrial fibrillation (NVAF). Meanwhile, in the Netherlands, NOACs are widely used next to VKAs. The objective of this study is to estimate the cost-effectiveness of treatment with rivaroxaban compared to VKAs in NVAF and VTE patients in the Netherlands, using data from international prospective observational phase IV studies.

Methods: Two models were developed to represent NVAF and VTE patients, populated with patients from the XANTUS (NCT01606995) and XALIA (NCT01619007) international prospective observational studies. The 1-year cost-effectiveness of rivaroxaban use, compared to VKAs, was explored in a population consisting of NVAF and VTE patients (base case) as well as for four scenarios with sub-populations: NVAF patients only, VTE patients only, NVAF patients with unstable international normalized ratio (INR), and NVAF patients using an INR self-measuring device.

Results: In the base case, rivaroxaban saved €72,350 and gained 21 quality-adjusted life-years (QALYs) in a simulation of 2,000 patients over the use of VKAs. Ergo, rivaroxaban was dominant over VKAs. The probabilistic sensitivity analysis showed a probability of 85% for rivaroxaban being dominant and 100% at a willingness-to-pay threshold of €20,000/QALY. Rivaroxaban appeared to be dominant in all scenarios as well, except for the NVAF-patients-only scenario where the incremental cost-effectiveness ratio (ICER) was €157/QALY.

Conclusions: In patients with NVAF or VTE, rivaroxaban treatment is likely to be cost-effective and a potentially cost-saving alternative to VKA in the Netherlands.     

Economic burden of thromboembolic and hemorrhagic complications in non-valvular atrial fibrillation in Algeria (the ELRAGFA study)

Abstract

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia, with substantial public health and economic impact on healthcare systems due to the prevention and management of thromboembolic and hemorrhagic complications. In Algeria, stroke is a leading cause of death, representing 15.6% of all deaths in 2012. Current data on the epidemiology and costs associated with non-valvular AF (NVAF) in Algeria are not available.

Methods: A three-step approach was undertaken to estimate the economic burden of NVAF in Algeria. First, a literature review identified the epidemiological burden of the disease. Second, expert clinicians practicing in Algerian hospitals were surveyed on consumed resources and unit costs of treatment and management of complications and prevention. Finally, these data were combined with event probabilities in an economic model to estimate the annual cost of NVAF prevention and complications for the Algerian healthcare system.

Results: Based on literature and demographics data, it was estimated that there are currently 187,686 subjects with NVAF in Algeria. Seventy per cent of this population was treated for prevention, half of which were controlled. Cost of prevention was estimated at 203 million DZD (€1.5 million) for drugs and 349 million DZD (€2.6 million) for examinations. Mean hospitalization costs for complications ranged between 123,500 and 435,500 DZD (€910–3,209), according to the type and severity of complications. Hospitalization costs for thromboembolic and hemorrhagic complications were estimated at 8,313 million DZD (€62 million), half of which was for untreated patients. Finally, the economic burden of NVAF was estimated at 8,865 million DZD (>€65 million) annually.

Conclusion: The economic burden of NVAF is important in Algeria, largely driven by untreated and INR-uncontrolled patients. There is a lack of information on the Algerian healthcare system that could increase uncertainty around this assessment, but it clearly establishes the importance of NVAF as a public health concern.     

Real-life cost of vitamin K antagonist treatment in patients with non-valvular atrial fibrillation in France in 2013

Aims: Data highlighting the cost drivers for non-valvular atrial fibrillation (NVAF) patients in terms of vitamin K antagonist (VKA) treatment and monitoring are lacking in France. This study aimed to evaluate the real-life daily cost of VKA treatment in 2013, in French patients suffering from NVAF.

Methods: This longitudinal observational study was performed using the EGB (Echantillon Généraliste des Bénéficiaires) database, a random sample of the French national insurance (NHI) database, which covers 80% of the population. All adult patients whose first NVAF anticoagulant treatment in 2013 was a VKA were analyzed. Costs were calculated for the duration of follow-up and then divided by the number of days of therapy. The analysis was performed both from the French NHI perspective (amount reimbursed by the NHI) and from a collective perspective.

Results: In this study, 3,254 NVAF patients treated with VKA in 2013 were included, and this sample comprised 52.6% males. The mean daily cost of VKA treatment was €1.13 (±1.18) according to the collective perspective (89.4% of this cost was associated to INR measurement) and €1.05 (±1.16) according to the NHI perspective.

Limitations: As diagnoses associated with procedures are not available in the EGB database, proxies were used, and an algorithm was created to define the AF population.

Conclusions: This analysis is the first to consider an exhaustive spectrum of the costs of VKA treatment in France using EGB data. VKA medication requires exhaustive follow-up, and, thus, associated costs are important. The results of the present study confirmed this close follow-up for VKA patients, making the cost of treatment by VKA nearly 10-times more expensive than the cost of medication itself.     

Cost-effectiveness of rivaroxaban versus apixaban for the initial treatment of venous thromboembolism and extended prevention of recurrences in the UK

Abstract

Aim: To evaluate the relative cost-effectiveness of using rivaroxaban vs apixaban for the initial treatment plus extended prevention of venous thromboembolism (VTE) in the UK. Extended prevention was assessed using a 10-mg rivaroxaban dose, as the 20-mg dose has already been evaluated.

Methods: A Markov model compared the health outcomes and costs of treating VTE patient cohorts with either rivaroxaban (15?mg twice daily for 3 weeks, followed by 20?mg once daily for 6 months, then extended prevention with 10?mg once daily) or apixaban (10?mg twice daily for 1 week, followed by 5?mg twice daily for 6 months, then extended prevention with 2.5?mg twice daily) over a lifetime horizon. The model included an initial acute treatment and prevention phase (0–6?months) and an extended prevention phase (6–18 months). Efficacy and safety data were derived from two network meta-analyses. Reference treatment comparators were derived from the EINSTEIN-Pooled study and EINSTEIN-CHOICE trial. Healthcare costs and utility data were derived from published literature.

Results: The rivaroxaban regimen was associated with increased quality-adjusted life years (QALYs) and slightly lower total costs compared with apixaban over a lifetime horizon. Deterministic and probabilistic sensitivity analyses demonstrated that rivaroxaban remained a cost-effective alternative to apixaban over a wide range of parameters. Incremental cost-effectiveness ratio estimates were below the £20,000 per QALY threshold in 74.1% of 2,000 model simulations. Scenario analyses further supported that rivaroxaban is a cost-effective alternative to apixaban.

Limitations: Clinical and safety inputs were derived from network meta-analysis, which are subject to inherent limitations whereby small differences between study designs may severely impact efficacy and safety outcomes. Furthermore, these inputs were based on data from clinical trials, which may not reflect real-world data.

Conclusions: Rivaroxaban was associated with a slightly lower total cost and increased QALYs compared with apixaban for VTE management in the UK over a lifetime horizon.     

Daily costs of hospitalization in non-valvular atrial fibrillation patients treated with anticoagulant therapy

Abstract

Background:

Atrial fibrillation (AF) is the most common cardiac rhythm disturbance in the US, with an estimated prevalence of 2.7–6.1 million persons in 2010.