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.     

Healthcare costs of stroke and major bleeding in patients with atrial fibrillation treated with non-vitamin K antagonist oral anticoagulants

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?p?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.     

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.     

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.     

心房颤动患者卒中防治药物利伐沙班与华法林的药物经济学分析

目的 对心房颤动患者卒中防治药物利伐沙班与华法林进行药物经济学评价.方法 本研究对心房颤动卒中的患者制订了两种治疗方案,华法林片(A组)、利伐沙班片(B组),运用药物经济学知识(成本-效果分析及敏感性分析)对利伐沙班和华法林预防心房颤动相关卒中进行药物经济学评价.结果 利伐沙班组与华法林组比较增量成本-效果比(ICER...     

Use of insertable cardiac monitors for the detection of atrial fibrillation in patients with cryptogenic stroke in the United States is cost-effective

Abstract

Objectives: Atrial fibrillation (AF) is the most common arrhythmia and a major marker of ischemic stroke risk. Early detection is crucial and, once diagnosed, anticoagulation therapy can be initiated to reduce stroke risk. The aim of this study was to assess the cost-effectiveness of employing an insertable cardiac monitor (ICM), BIOMONITOR, for the detection of AF compared to standard of care (SoC) ECG and Holter monitoring in patients with cryptogenic stroke, that is, stroke of unknown origin and where paroxysmal, silent AF is suspected.

Materials and methods: A Markov model was developed which consisted of five main health states reflecting the potential lifetime evolution of the AF disease: post cryptogenic stroke (index event), subsequent mild, moderate and severe stroke, and death. Sub-states were included to track a patient’s AF diagnostic status and the use of antiplatelet or anticoagulant therapy. AF detection was assumed to result in a treatment switch from aspirin to anticoagulants, except among those with a history of major bleeding. Detection yield and accuracy, clinical actions and treatment effects were derived from the literature and validated by an expert clinician. All relevant costs from a US Medicare perspective were included.

Results and conclusions: An ICM-based strategy was associated with a reduction of 37 secondary ischemic strokes per 1000 patients monitored compared with SoC. Total per-patient costs with an ICM were higher (US$90,052 vs. US$85,157) although stroke-related costs were reduced. The use of an ICM was associated with a base-case incremental cost-effectiveness ratio of US$18,487 per life year gained compared with SoC and US$25,098 per quality-adjusted life year gained, below established willingness-to-pay thresholds. The conclusions were found to be robust over a range of input values. From a US Medicare perspective the use of a BIOMONITOR ICM represents a cost-effective diagnostic strategy for patients with cryptogenic stroke and suspected AF.     

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.     

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.     

Medical costs in the US of clinical events associated with oral anticoagulant (OAC) use compared to warfarin among non-valvular atrial fibrillation patients ≥75 and <75 years of age,based on the ARISTOTLE,RE-LY,and ROCKET-AF trials

Abstract

Objectives:

Based on clinical trials the oral anticoagulants (OACs) apixaban, dabigatran, and rivaroxaban are efficacious for reducing stroke risk for non-valvular atrial fibrillation (NVAF) patients. Based on the clinical trials, this study evaluated the medical costs for clinical events among NVAF patients ≥75 and <75 years of age treated with individual OACs vs warfarin.

Methods:

Rates for primary and secondary efficacy and safety outcomes (i.e., clinical events) among NVAF patients receiving warfarin or each of the OACs were determined for NVAF populations aged ≥75 years and <75 years of age from the OAC vs warfarin trials. One-year incremental costs among patients with clinical events were obtained from published literature and inflation adjusted to 2010 costs. Medical costs, excluding medication costs, for clinical events associated with each OAC and warfarin were then estimated and compared.

Results:

Among NVAF patients aged ≥75, compared to warfarin, use of either apixaban or rivaroxaban was associated with a reduction in medical costs per patient year (apixaban?=??$825, rivaroxaban?=?$23), while dabigatran use was associated with increased medical costs of $180 per patient year. Among NVAF patients <75 years of age medical costs per patient year were estimated to be reduced ?$254, ?$367, and ?$88, for apixaban, dabigatran, and rivaroxaban, respectively, in comparison to warfarin.

Limitations:

This economic analysis was based on clinical trial data and, therefore, the direct application of the results to routine clinical practice will require further assessment.

Conclusions:

Difference in medical costs between OAC and warfarin treated NVAF patients vary by age group and individual OACs. Although reductions in medical costs for NVAF patients aged ≥75 and <75 were observed for those using either apixaban or rivaroxaban vs warfarin, the reductions were greater per patient year for both the older and younger NVAF populations using apixaban.     

Predictors for total hospital and cardiology cost claims among patients with atrial fibrillation initiating dabigatran or acenocoumarol in The Netherlands

Aims: The prevalence of atrial fibrillation (AF) has increased over the past years due to aging of the population, and healthcare costs associated with AF reflect a significant financial burden. The aim of this study was to explore predictors for the real-world AF-related in-hospital costs in patients that recently initiated anticoagulation with acenocoumarol or dabigatran.

Methods: Predictors for claimed total hospital care costs and cardiology costs in AF patients were explored by using hospital financial claims data from propensity score matched patient groups in a large Dutch community hospital. This study analyzed the total dataset (n?=?766) and carried out a secondary analysis for all matched pairs of anticoagulation naïve AF patients (n?=?590) by ordinal regression.

Results: Dabigatran was a predictor for significantly lower cardiology and total hospital care costs (Odds Ratio [OR]?=?0.43, 95% confidence interval (CI)?=?0.33–0.57; and OR?=?0.60, 95% CI?=?0.46–0.79, respectively). Female gender was a predictor for lower total hospital care costs. Predictors for an increase in total hospital care costs were the occurrence of stroke or systemic embolism, major bleeding, and minor bleeding. The costs predictors were comparable when limiting the analysis to patients that were anticoagulation naïve. Age and CHA₂DS₂-VASc were not predictors for either cardiology or total hospital care costs in both analyses.

Conclusion: Dabigatran treatment was as a predictor for lower cardiology costs and lower total hospital care costs in AF patients that initiated oral anticoagulation.