Health economic evaluation of nation-wide screening programmes for atrial fibrillation in the Netherlands.

AIMS: Screening for atrial fibrillation (AF) is recommended by the European Society of Cardiology guidelines to prevent strokes. Cost-effectiveness analyses of different screening programmes for AF are difficult to compare because of varying settings and models used. We compared the impact and cost-effectiveness of various AF screening programmes in the Netherlands. METHODS AND RESULTS: 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 ARISTOTLE, RE-LY, and ROCKET AF trials combined with Dutch observational data. Univariate, probabilistic sensitivity, and various scenario analyses were performed. The maximum number of newly detected AF patients in the Netherlands ranged from 4554 to 39 270, depending on the screening strategy used. Adequate treatment with anticoagulation would result in a maximum of >3000 strokes prevented using single-time point AF screening. Compared with no screening, screening 100 000 people provided a gain in QALYs ranging from 984 to 8727 and a mean cost difference ranging from -6650 000€ to 898 000€, depending on the screening strategy used. The probabilistic sensitivity analysis (PSA) demonstrated a 100% likelihood that screening all patients ≥75 years visiting the geriatric outpatient clinic was cost-saving. Four out of six strategies were cost-saving in ≥74% of the PSA simulations. Out of these, opportunistic screening of all patients ≥65 years visiting the GPs office had the highest impact on strokes prevented. CONCLUSION: Most single-time point AF screening strategies are cost-saving and have an important impact on stroke prevention.

Lean Body Mass and Total Body Weight Versus Body Surface Area as a Determinant of Docetaxel Pharmacokinetics and Toxicity.

AIM: This study examined whether anthropometric and body composition parameters such as body surface area (BSA), lean body mass (LBM), and total body weight (TBW) are correlated with docetaxel clearance and exposure by analyzing area under the curve. In addition, LBM, TBW, and a fixed dose were compared with BSA as dosing parameters for dose individualization of docetaxel. METHODS: Thirty-six patients receiving docetaxel chemotherapy for breast or metastatic castration-resistant prostate carcinoma were included. Before treatment, LBM was measured using a dual-energy X-ray absorptiometry scanner. Blood samples were collected up to 180 minutes after dosing to analyze docetaxel concentrations and determine individual pharmacokinetic parameters. RESULTS: No significant correlations were found between docetaxel clearance and the anthropometric and body composition variables (BSA, LBM, and TBW). The area under the curve was significantly but poorly correlated with BSA [r = 0.452 ( P = 0.016)] and TBW [r = 0.476 ( P = 0.011)]. The mean absolute percentage error and mean error of simulated dosing based on LBM and fixed dosing were not significantly different from those of BSA. For TBW, only mean absolute percentage error was significantly higher compared with dosing based on BSA (24.1 versus 17.1, P = 0.001). CONCLUSIONS: There was no clinically relevant correlation between docetaxel pharmacokinetics and the anthropometric and body composition variables BSA, LBM, and TBW. Therefore, dose individualization of docetaxel based on LBM, TBW, or fixed dosing cannot be recommended over BSA-based dosing.

Leveraging the Similarities Between Cost-Effectiveness Analysis and Value-Based Healthcare.

OBJECTIVES: This article aims to explore overlaps and differences between the emerging concept of value-based healthcare (VBHC) and the established field of cost-effectiveness analysis (CEA), as well as the feasibility of integrating them together. Interest in VBHC has grown significantly in developed countries that seek to preserve the sustainability of their healthcare systems. Consequently, it is likely that VBHC will soon play a meaningful role in health economic policy and decision making. Because VBHC and CEA share many similarities, academics have pointed out that integration could lead to opportunities for improvements in both fields. METHODS: An exploration of overlapping topics in VBHC and CEA literature was performed to establish initial links between them. A new methodologic approach is described to consolidate key value frameworks from the respective fields. RESULTS: Several key themes emerged in which these 2 concepts can reinforce each other: interpretation of value, sensitivity to outcome changes, scientific credibility, methodology and measurement, and usability in decision making. Subsequently, an initial method is described of how the VBHC framework for value could be integrated into CEA through a so-called value-based healthcare quality-adjusted life year (VBHC-QALY). CONCLUSION: This article introduces the existing VBHC value framework to the cornerstone of modern CEA and substantiates the presumption of health economists that valuable synergies arise from consolidating the individual strengths of CEA and VBHC. Through integration CEA can help establish robust methods for VBHC implementation, while the latter can complement the former with a new viewpoint and conceptual toolbox for patient centricity and the definition of value.

Incidence, treatment and mortality of new-onset atrial fibrillation patients at the intensive care unit.

Objective: Critically ill patients admitted to the intensive care unit (ICU) often develop atrial fibrillation (AF), with an incidence of around 5%. Stroke prevention in AF is well described in clinical guidelines. The extent to which stroke prevention is prescribed to ICU patients with AF is unknown. We aimed to determine the incidence of new-onset AF and describe stroke prevention strategies initiated on the ICU of our teaching hospital. Also, we compared mortality in patients with new-onset AF to critically ill patients with previously diagnosed AF and patients without any AF. Methods: This study was a retrospective cohort study including all admissions to the ICU of the Martini Hospital (Groningen, The Netherlands) in the period 2011 to 2016. Survival analyses were performed using these real-world data. Results: In total, 3334 patients were admitted to the ICU, of whom 213 patients (6.4%) developed new-onset AF. 583 patients (17.5%) had a previous AF diagnosis, the other patients were in sinus rhythm. In-hospital mortality and 1-year mortality after hospital discharge were significantly higher for new-onset AF patients compared with patients with no history of AF or previously diagnosed AF. At hospital discharge, only 56.3% of the new-onset AF-patients eligible for stroke prevention received an anticoagulant. Anticoagulation was not dependent on CHA2DS2-VASc score or other patient characteristics. An effect of anticoagulative status on mortality was not significant. Conclusion: AF is associated with increased mortality in critically ill patients admitted to the ICU. More guidance is needed to optimise anticoagulant treatment in critically ill new-onset AF patients.

Atrial Fibrillation in Africa-An Under-Reported and Unrecognized Risk Factor for Stroke: A Systematic Review.

Over three-quarters of deaths from cardiovascular disease and diabetes occur in low- and middle-income countries, which include many African countries. Global studies showed that the prevalence of the cardiac arrhythmia atrial fibrillation (AF) appeared to be lower in Africa. A systematic search of PubMed and African Journals Online was conducted to determine the prevalence of AF and associated stroke risk factors in Africa and to quantify the need for screening. The publications search yielded a total of 840 articles of which 41 were included. AF was often not identified as the disease of primary interest with its own risks. Data on prevalence in the general population was scarce. The prevalence of stroke risk factors showed a large variation between studies, as well as within clustered subpopulations. AF in Africa is under-reported in published reports. The study types and populations are highly heterogeneous, making it difficult to draw a definitive conclusion on AF prevalence.

Perioperative bridging of vitamin K antagonist treatment in patients with atrial fibrillation: only a very small group of patients benefits.

AIMS: Bridging anticoagulation in atrial fibrillation (AF) patients who need to interrupt vitamin K antagonists for procedures is a clinical dilemma. Currently, guidelines recommend clinicians to take the stroke and bleeding risk into consideration, but no clear thresholds are advised. To aid clinical decision making, we aimed to develop a model in which periprocedural bridging therapy is compared with withholding anticoagulation in AF patients, for several bleeding and stroke risk groups. METHODS AND RESULTS: A model was developed to simulate both a bridge and a non-bridge cohort, using simulated international normalized ratio (INR) values for patients on warfarin, acenocoumarol, and phenprocoumon. For both clinical strategies, stroke and bleeding risks were included and outcomes were stratified by CHA2DS2-VASc or CHADS2 and HAS-BLED groups. Quality-adjusted life expectancy was the main outcome considered. Our analyses show bridging to only be beneficial for patients with HAS-BLED scores equal or lower to 2 and with CHA2DS2-VASc scores of 6 or higher. For patients using acenocoumarol bridging may be beneficial starting at a CHA2DS2-VASc score of 7. Post-procedural time to therapeutic INR has a significant influence on the results: no significant benefit of bridging was found for patients reaching therapeutic INR values within 5 days. CONCLUSION: When deciding whether to bridge anticoagulation, clinicians should consider the patient's individual stroke and bleeding risk, while also considering the patient's post-procedural INR management. In practice, only a small subset of patients is expected to benefit from bridging anticoagulation treatment.

Secondary adherence to non-vitamin-K antagonist oral anticoagulants in patients with atrial fibrillation in Sweden and the Netherlands.

OBJECTIVE: There is limited evidence on patients' adherence and the impact of the prescribed dosing regimen in non-vitamin-K oral anticoagulants (NOACs). We aimed to assess secondary adherence to NOACs and to determine the impact of the dosing regimen in patients with atrial fibrillation. METHODS: Patients using a NOAC between 2009 and 2013 were identified from the nation-wide Swedish Prescribed Drug Register and the Dutch regional IADB.nl database. Patients using a consistent dosage for at least 180 consecutive days were included. Adherence was calculated using the medication possession ratio (MPR) and adjusted for overlapping dates. Adherence was defined as a MPR ≥0.8. Sensitivity analyses were performed using a MPR ≥0.9. Logistic regression was performed to compare secondary adherence and to explore the influence of the dosing regimen. RESULTS: A total of 5254 Swedish and 430 Dutch NOAC users were included. The mean MPR was 96.0% (SD 7.8%) in Sweden and 95.1% (SD 10.1%) in the Netherlands. Multivariable logistic regression analysis showed that a twice daily regimen had a lower likelihood of being secondary adherent compared to a once daily regimen in Sweden (odds ratio [OR] 0.21 [95% CI 0.12-0.35]). LIMITATIONS: The influence of selection bias introduced by the inclusion criterion of ≥2 dispensations covering at least 180 days could not be excluded. CONCLUSIONS: This study demonstrated that secondary adherence was high in this specific setting among patients with at least two initial dispensations of a NOAC covering a minimum of 180 days. The use of NOACs in a once daily regimen showed higher adherence compared to a twice daily regimen.

Cost-effectiveness of screening for atrial fibrillation in primary care with a handheld, single-lead electrocardiogram device in the Netherlands.

Aims: Atrial fibrillation (AF) is the most common arrhythmia and prevalence increases with age. Patients with AF have a high risk of stroke, and screening for AF is recommended in all people aged 65 years or older to identify patients eligible for stroke prevention. A handheld, single-lead electrocardiogram (ECG) device can be used for systematic screening in the population at risk. The objective of this study is to estimate the cost-effectiveness of screening for AF in primary care with the MyDiagnostick® during seasonal influenza vaccination in the Netherlands. Methods and results: Lifetime costs and effects of a single screening session for AF detection were assessed from a societal perspective with a decision analytic model consisting of a straightforward decision tree and a joining Markov model. The decision model simulated all patients aged 65 years and over attending the seasonal influenza vaccination in the Netherlands. Event probabilities were derived from clinical trials. Sensitivity analyses were performed to assess the impact of important model assumptions as well as determining the relative effect of individual parameters. Screening for AF with the MyDiagnostick® in all patients older than 65 years that attend seasonal influenza vaccination in the Netherlands would decrease the overall costs by €764 and increase the quality-adjusted life-years (QALYs) by 0.27 years per patient. Early detection of AF would prevent strokes and leads to beneficial health effects with subsequent cost savings. This screening method would have an estimated probability of 99.8% for being cost-effective at a conservative willingness-to-pay of €20 000/QALY. Conclusion: Screening for AF in primary care with a handheld, single-lead ECG during seasonal influenza vaccination is very likely to be cost saving for identifying new cases of AF in the Dutch population aged 65 years and over. Active screening for AF with a single-lead, handheld ECG device during seasonal influenza vaccination could be implemented in primary care.

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.

Health economic evaluation of rivaroxaban in elective cardioversion of atrial fibrillation.

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

Ready-to-use parenteral amiodarone: a feasibility study towards a long-term stable product formulation.

OBJECTIVES: To determine the feasibility of preparing a long-term stable ready-to-use parenteral amiodarone formulation using cyclodextrins as dissolution enhancer. METHODS: A preformulation study was performed with different molar ratios of hydroxypropyl-beta-cyclodextrin (HP-BCD) or sulfobutylether-beta-cyclodextrin (SBE-BCD) to amiodarone in order to investigate enhancement of amiodarone's water solubility. Further, effects of pH and temperature on the dissolution rate during production were investigated. Shelf-life was determined for a ready-to-use iso-osmotic preparation of 1.8 mg/mL amiodarone with SBE-BCD in a molar ratio of 1:3. Amiodarone content was assessed using a validated high-pressure liquid chromatography ultraviolet method. RESULTS: Amiodarone-SBE-BCD in a molar ratio of 1:3 at pH 4.0-5.0 yielded the best results in terms of increased solubility and dissolution time (90 min). With SBE-BCD, a smaller molar ratio to amiodarone was needed than with HP-BCD. The amiodarone content of the final formulation stored 12 months at 21°C in daylight remained unchanged. CONCLUSIONS: A ready-to-use or ready-to-administer amiodarone product, prepared in a hospital pharmacy, for intravenous application in an acute clinical setting is a feasible option from a chemical, physical and microbiological point of view. The availability of such a product will have a significant impact on medication safety, and production should therefore be considered.