Patients on vitamin K treatment: is switching to direct-acting oral anticoagulation cost-effective? A target trial on a prospective cohort.

AIMS: Direct-acting oral anticoagulants (DOACs) have, to a substantial degree, replaced vitamin K antagonists (VKA) as treatments for stroke prevention in atrial fibrillation (AF) patients. However, evidence on the real-world causal effects of switching patients from VKA to DOAC is lacking. We aimed to assess the empirical incremental cost-effectiveness of switching patients to DOAC compared with maintaining VKA treatment. METHODS: The target trial approach was applied to the prospective observational Swiss-AF cohort, which enrolled 2415 AF patients from 2014 to 2017. Clinical data, healthcare resource utilisation and EQ-5D-based utilities representing quality of life were collected in yearly follow-ups. Health insurance claims were available for 1024 patients (42.4%). Overall survival, quality-of-life, costs from the Swiss statutory health insurance perspective and cost-effectiveness were estimated by emulating a target trial in which patients were randomly assigned to switch to DOAC or maintain VKA treatment. RESULTS: 228 patients switching from VKA to DOAC compared with 563 patients maintaining VKA treatment had no overall survival advantage over a 5-year observation period (HR 0.99, 95% CI 0.45, 1.55). The estimated gain in quality-adjusted life years (QALYs) was 0.003 over the 5-year period at an incremental costs of CHF 23 033 (€ 20 940). The estimated incremental cost-effectiveness ratio was CHF 425 852 (€ 387 138) per QALY gained. CONCLUSIONS: Applying a causal inference method to real-world data, we could not demonstrate switching to DOACs to be cost-effective for AF patients with at least 1 year of VKA treatment. Our estimates align with results from a previous randomised trial.

Longitudinal Changes in Health-Related Quality of Life in Patients With Atrial Fibrillation.

Background Optimizing health-related quality of life (HRQoL) is an important aim of atrial fibrillation (AF) treatment. Little is known about patients' long-term HRQoL trajectories and the impact of patient and disease characteristics. The aim of this study was to describe HRQoL trajectories in an observational AF study population and in clusters of patients with similar patient and disease characteristics. Methods and Results We used 5-year follow-up data from the Swiss-Atrial Fibrillation prospective cohort, which enrolled 2415 patients with prevalent AF from 2014 to 2017. HRQoL data, collected yearly, comprised EuroQoL-5 dimension utilities and EuroQoL visual analog scale scores. Patient clusters with similar characteristics at enrollment were identified using hierarchical clustering. HRQoL trajectories were analyzed descriptively and with inverse probability-weighted regressions. Effects of postbaseline clinical events were additionally assessed using time-shifted event variables. Among 2412 (99.9%) patients with available baseline HRQoL, 3 clusters of patients with AF were identified, which we characterized as follows: "cardiovascular dominated," "isolated symptomatic," and "severely morbid without cardiovascular disease." Utilities and EuroQoL visual analog scale scores remained stable over time for the full population and the clusters; isolated symptomatic patients showed higher levels of HRQoL. Utilities were reduced after occurrences of stroke, hospitalization for heart failure, and bleeding, by -0.12 (95% CI, -0.18 to -0.06), -0.10 (95% CI, -0.13 to -0.08), and -0.06 (95% CI, -0.08 to -0.04), respectively, on a 0 to 1 utility scale. Utility of surviving patients returned to preevent levels 4 years after heart failure hospitalization; 3 years after bleeding; and 1 year after stroke. Conclusions In patients with prevalent AF, HRQoL was stable over time, irrespective of baseline patient characteristics. Clinical events of hospitalization for heart failure, stroke, and bleeding had only a temporary effect on HRQoL.

Estimating the cost impact of atrial fibrillation using a prospective cohort study and population-based controls.

AIMS: Atrial fibrillation (AF) costs are expected to be substantial, but cost comparisons with the general population are scarce. Using data from the prospective Swiss-AF cohort study and population-based controls, we estimated the impact of AF on direct healthcare costs from the Swiss statutory health insurance perspective. METHODS: Swiss-AF patients, enrolled from 2014 to 2017, had documented, prevalent AF. We analysed 5 years of follow-up, where clinical data, and health insurance claims in 42% of the patients were collected on a yearly basis. Controls from a health insurance claims database were matched for demographics and region. The cost impact of AF was estimated using five different methods: (1) ordinary least square regression (OLS), (2) OLS-based two-part modelling, (3) generalised linear model-based two-part modelling, (4) 1:1 nearest neighbour propensity score matching and (5) a cost adjudication algorithm using Swiss-AF data non-comparatively and considering clinical data. Cost of illness at the Swiss national level was modelled using obtained cost estimates, prevalence from the Global Burden of Disease Project, and Swiss population data. RESULTS: The 1024 Swiss-AF patients with available claims data were compared with 16 556 controls without known AF. AF patients accrued CHF5600 (EUR5091) of AF-related direct healthcare costs per year, in addition to non-AF-related healthcare costs of CHF11100 (EUR10 091) per year accrued by AF patients and controls. All five methods yielded comparable results. AF-related costs at the national level were estimated to amount to 1% of Swiss healthcare expenditure. CONCLUSIONS: We robustly found direct medical costs of AF patients were 50% higher than those of population-based controls. Such information on the incremental cost burden of AF may support healthcare capacity planning.

Real-World Cost-Effectiveness of Pulmonary Vein Isolation for Atrial Fibrillation: A Target Trial Approach.

OBJECTIVES: Randomized controlled trials of pulmonary vein isolation (PVI) for treating atrial fibrillation (AF) have proven the procedure's efficacy. Studies assessing its empirical cost-effectiveness outside randomized trial settings are lacking. We aimed to evaluate the effectiveness and cost-effectiveness of PVI versus medical therapy for AF. METHODS: We followed a target trial approach using the Swiss-AF cohort, a prospective observational cohort study that enrolled patients with AF between 2014 and 2017. Resource utilization and cost information were collected through claims data. Quality of life was measured with EQ-5D-3L utilities. We estimated incremental cost-effectiveness ratios (ICERs) from the perspective of the Swiss statutory health insurance system. RESULTS: Patients undergoing PVI compared with medical therapy had a 5-year overall survival advantage with a hazard ratio of 0.75 (95% CI 0.46-1.21; P = .69) and a 19.8% SD improvement in quality of life (95% CI 15.5-22.9; P < .001), at an incremental cost of 29 604 Swiss francs (CHF) (95% CI 16 354-42 855; P < .001). The estimated ICER was CHF 158 612 per quality-adjusted life-year (QALY) gained within a 5-year time horizon. Assuming similar health effects and costs over 5 additional years changed the ICER to CHF 82 195 per QALY gained. Results were robust to the sensitivity analyses performed. CONCLUSIONS: Our results show that PVI might be a cost-effective intervention within the Swiss healthcare context in a 10-year time horizon, but unlikely to be so at 5 years, if a willingness-to-pay threshold of CHF 100 000 per QALY gained is assumed. Given data availability, we find target trial designs are a valuable tool for assessing the cost-effectiveness of healthcare interventions outside of randomized controlled trial settings.

Patient clusters and cost trajectories in the Swiss Atrial Fibrillation cohort.

OBJECTIVE: Evidence on long-term costs of atrial fibrillation (AF) and associated factors is scarce. As part of the Swiss-AF prospective cohort study, we aimed to characterise AF costs and their development over time, and to assess specific patient clusters and their cost trajectories. METHODS: Swiss-AF enrolled 2415 patients with variable duration of AF between 2014 and 2017. Patient clusters were identified using hierarchical cluster analysis of baseline characteristics. Ongoing yearly follow-ups include health insurance clinical and claims data. An algorithm was developed to adjudicate costs to AF and related complications. RESULTS: A subpopulation of 1024 Swiss-AF patients with available claims data was followed up for a median (IQR) of 3.24 (1.09) years. Average yearly AF-adjudicated costs amounted to SFr5679 (€5163), remaining stable across the observation period. AF-adjudicated costs consisted mainly of inpatient and outpatient AF treatment costs (SFr4078; €3707), followed by costs of bleeding (SFr696; €633) and heart failure (SFr494; €449). Hierarchical analysis identified three patient clusters: cardiovascular (CV; N=253 with claims), isolated-symptomatic (IS; N=586) and severely morbid without cardiovascular disease (SM; N=185). The CV cluster and SM cluster depicted similarly high costs across all cost outcomes; IS patients accrued the lowest costs. CONCLUSION: Our results highlight three well-defined patient clusters with specific costs that could be used for stratification in both clinical and economic studies. Patient characteristics associated with adjudicated costs as well as cost trajectories may enable an early understanding of the magnitude of upcoming AF-related healthcare costs.

Association of pulmonary vein isolation and major cardiovascular events in patients with atrial fibrillation.

BACKGROUND: Patients with atrial fibrillation (AF) face an increased risk of adverse cardiovascular events. Evidence suggests that early rhythm control including AF ablation may reduce this risk. METHODS: To compare the risks for cardiovascular events in AF patients with and without pulmonary vein isolation (PVI), we analysed data from two prospective cohort studies in Switzerland (n = 3968). A total of 325 patients who had undergone PVI during a 1-year observational period were assigned to the PVI group. Using coarsened exact matching, 2193 patients were assigned to the non-PVI group. Outcomes were all-cause mortality, hospital admission for acute heart failure, a composite of stroke, transient ischemic attack and systemic embolism (Stroke/TIA/SE), myocardial infarction (MI), and bleedings. We calculated multivariable adjusted Cox proportional-hazards models. RESULTS: Overall, 2518 patients were included, median age was 66 years [IQR 61.0, 71.0], 25.8% were female. After a median follow-up time of 3.9 years, fewer patients in the PVI group died from any cause (incidence per 100 patient-years 0.64 versus 1.87, HR 0.39, 95%CI 0.19-0.79, p = 0.009) or were admitted to hospital for acute heart failure (incidence per 100 patient-years 0.52 versus 1.72, HR 0.44, 95%CI 0.21-0.95, p = 0.035). There was no significant association between PVI and Stroke/TIA/SE (HR 0.94, 95%CI 0.52-1.69, p = 0.80), MI (HR 0.43, 95%CI 0.11-1.63, p = 0.20) or bleeding (HR 0.75, 95% CI 0.50-1.12, p = 0.20). CONCLUSIONS: In our matched comparison, patients in the PVI group had a lower incidence rate of all-cause mortality and hospital admission for acute heart failure compared to the non-PVI group. GOV IDENTIFIER: NCT02105844, April 7th 2014.

Sources of confidence in value-based choice.

Confidence, the subjective estimate of decision quality, is a cognitive process necessary for learning from mistakes and guiding future actions. The origins of confidence judgments resulting from economic decisions remain unclear. We devise a task and computational framework that allowed us to formally tease apart the impact of various sources of confidence in value-based decisions, such as uncertainty emerging from encoding and decoding operations, as well as the interplay between gaze-shift dynamics and attentional effort. In line with canonical decision theories, trial-to-trial fluctuations in the precision of value encoding impact economic choice consistency. However, this uncertainty has no influence on confidence reports. Instead, confidence is associated with endogenous attentional effort towards choice alternatives and down-stream noise in the comparison process. These findings provide an explanation for confidence (miss)attributions in value-guided behaviour, suggesting mechanistic influences of endogenous attentional states for guiding decisions and metacognitive awareness of choice certainty.