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.

Valor pronóstico de las frecuencias cardiacas bajas en pacientes ingresados con infarto agudo de miocardio / Prognostic value of low heart rates in patients admitted with acute myocardial infarction

Introducción y objetivos: Las escalas de predicción de riesgo utilizadas en síndromes coronarios agudos (SCA) utilizan modelos incrementales para estimar mortalidad para frecuencias cardiacas (FCs)> 60 lpm. Sin embargo, estudios previos comunicaron una relación no lineal entre la FC y los eventos, lo que sugiere que la FC baja puede tener un papel pronóstico no reconocido. El objetivo fue valorar el impacto pronóstico de las FCs baja en el SCA, definida como frecuencia cardiaca de admisión <50 lpm. Métodos: El estudio analizó datos del registro AMIS Plus, una cohorte de pacientes hospitalizados con SCA entre 1999 y 2021. El criterio de valoración principal fue la mortalidad hospitalaria por todas las causas, mientras que el compuesto de mortalidad por todas las causas se estableció por eventos cardiacos/cerebrovasculares mayores como secundario. Se adoptó una metodología estadística multinivel para evaluar el papel pronóstico de la FC baja en el SCA. Resultados: Se incluyó a 51.001 pacientes. La estimación cruda mostró una distribución bimodal de las variables resultados primaria y secundaria a FCs bajas y altas. Se observó una relación no lineal entre FCs y mortalidad intrahospitalaria mediante análisis restringido de spline cúbico. Una FC entre 50-75 mostró menor mortalidad que FC <50 lpm (OR=0,67; IC95%, 0,47-0,99) solo tras el análisis primario multivariado, no confirmado tras análisis múltiples de sensibilidad. Tras la puntuación de propensión emparejada, se hizo evidente el desvanecimiento progresivo del papel pronóstico de la FC <50 lpm. Conclusiones: Las FCs baja al ingreso en SCA se asocian a una mayor tasa cruda de eventos adversos. No obstante, tras la corrección de las diferencias basales, no se confirmó el papel pronóstico de la FC baja, sino que representa más bien un marcador de morbilidad subyacente. Estos resultados pueden ser clínicamente relevantes para mejorar la precisión de las puntuaciones de riesgo en el SCA.(AU)

Introduction and objectives: The risk prediction scores adopted in acute coronary syndromes (ACS) use incremental models to estimate mortality for heart rate (HR) above 60 bpm. Nonetheless, previous studies reported a nonlinear relationship between HR and events, suggesting that low HR may have an unrecognized prognostic role. We aimed to assess the prognostic impact of low HR in ACS, defined as admission HR <50 bpm. Methods: This study analyzed data from the AMIS Plus registry, a cohort of hospitalized patients with ACS between 1999 and 2021. The primary endpoint was in-hospital all-cause mortality, while a composite of all-cause mortality, major cardiac/cerebrovascular events was set as the secondary endpoint. A multilevel statistical method was used to assess the prognostic role of low HR in ACS. Results: The study included 51 001 patients. Crude estimates showed a bimodal distribution of primary and secondary endpoints with peaks at low and high HR. A nonlinear relationship between HR and in-hospital mortality was observed on restricted cubic spline analysis. An HR of 50 to 75 bpm showed lower mortality than HR <50 bpm (OR, 0.67; 95%CI, 0.47-0.99) only after primary multivariable analysis, which was not confirmed after multiple sensitivity analyses. After propensity score matching, progressive fading of the prognostic role of HR <50 bpm was evident. Conclusions: Low admission HR in ACS is associated with a higher crude rate of adverse events. Nonetheless, after correction for baseline differences, the prognostic role of low HR was not confirmed. Therefore, low HR probably represents a marker of underlying morbidity. These results may be clinically relevant in improving the accuracy of risk scores in ACS.(AU)

Twenty-year trends in the prevalence of modifiable cardiovascular risk factors in young acute coronary syndrome patients hospitalized in Switzerland.

AIMS: Modifiable cardiovascular risk factors (RFs) play a key role in the development of coronary artery disease. We evaluated 20-year trends in RF prevalence among young adults hospitalized with acute coronary syndromes (ACS) in Switzerland. METHODS AND RESULTS: Data were analysed from the Acute Myocardial Infarction in Switzerland (AMIS) Plus registry from 2000 to 2019. Young patients were defined as those aged <50 years. Among 58 028 ACS admissions, 7073 (14.1%) were young (median 45.6 years, IQR 42.0-48.0), of which 91.6% had at least one modifiable RF and 59.0% had at least two RFs. Smoking was the most prevalent RF (71.4%), followed by dyslipidaemia (57.3%), hypertension (35.9%), obesity (21.7%), and diabetes (10.1%). Compared with older patients, young patients were more likely to be obese (21.7% vs. 17.4%, P < 0.001) and active smokers (71.4% vs. 33.9%, P < 0.001). Among young patients, between 2000 and 2019, there was a significant increase in the prevalence of hypertension from 29.0% to 51.3% and obesity from 21.2% to 27.1% (both Ptrend < 0.001) but a significant decrease in active smoking from 72.5% to 62.5% (Ptrend = 0.02). There were no significant changes in the prevalence of diabetes (Ptrend = 0.32) or dyslipidaemia (Ptrend = 0.067). CONCLUSION: Young ACS patients in Switzerland exhibit a high prevalence of RFs and are more likely than older patients to be obese and smokers. Between 2000 and 2019, RF prevalence either increased or remained stable, except for smoking which decreased but still affected approximately two-thirds of young patients in 2019. Public health initiatives targeting RFs in young adults in Switzerland are warranted.

We evaluated the prevalence of risk factors (RFs) among young patients admitted with ACS in Switzerland between 2000 and 2019. Young ACS patients in Switzerland exhibited a high prevalence of RFs. There was a significant increase in the prevalence of hypertension and obesity. Despite a significant decrease, active smoking remained the most prevalent RF. These findings strongly suggest that public health initiatives targeting RFs in young adults in Switzerland are warranted.

Prognostic value of low heart rates in patients admitted with acute myocardial infarction.

INTRODUCTION AND OBJECTIVES: The risk prediction scores adopted in acute coronary syndromes (ACS) use incremental models to estimate mortality for heart rate (HR) above 60 bpm. Nonetheless, previous studies reported a nonlinear relationship between HR and events, suggesting that low HR may have an unrecognized prognostic role. We aimed to assess the prognostic impact of low HR in ACS, defined as admission HR <50 bpm. METHODS: This study analyzed data from the AMIS Plus registry, a cohort of hospitalized patients with ACS between 1999 and 2021. The primary endpoint was in-hospital all-cause mortality, while a composite of all-cause mortality, major cardiac/cerebrovascular events was set as the secondary endpoint. A multilevel statistical method was used to assess the prognostic role of low HR in ACS. RESULTS: The study included 51 001 patients. Crude estimates showed a bimodal distribution of primary and secondary endpoints with peaks at low and high HR. A nonlinear relationship between HR and in-hospital mortality was observed on restricted cubic spline analysis. An HR of 50 to 75 bpm showed lower mortality than HR <50 bpm (OR, 0.67; 95%CI, 0.47-0.99) only after primary multivariable analysis, which was not confirmed after multiple sensitivity analyses. After propensity score matching, progressive fading of the prognostic role of HR <50 bpm was evident. CONCLUSIONS: Low admission HR in ACS is associated with a higher crude rate of adverse events. Nonetheless, after correction for baseline differences, the prognostic role of low HR was not confirmed. Therefore, low HR probably represents a marker of underlying morbidity. These results may be clinically relevant in improving the accuracy of risk scores in ACS.

Reducing gap in pre-hospital delay between women and men presenting with ST-elevation myocardial infarction.

AIMS: This study aimed to analyse changes in pre-hospital delay over time in women and men presenting with ST-elevation myocardial infarction (STEMI) in Switzerland. METHODS AND RESULTS: AMIS Plus registry data of patients admitted for STEMI between 2002 and 2019 were analysed using multivariable quantile regression including the following covariates: interaction between sex and admission year, age, diabetes, pain at presentation, myocardial infarction (MI) history, heart failure history, hypertension, and renal disease. Among the 15,350 patients included (74.5% men), the median (interquartile range) delay between 2002 and 2019 was 150 (84; 345) min for men and 180 (100; 414) min for women. The unadjusted median pre-hospital delay significantly decreased over time for both sexes but the decreasing trend was stronger for women. Specifically, the unadjusted sex differences in delay decreased from 60 min in 2002 (P = 0.0042) to 40.5 min in 2019 (P = 0.165). The multivariable model revealed a significant interaction between sex and admission year (P = 0.038) indicating that the decrease in delay was stronger for women (-3.3 min per year) than for men (-1.6 min per year) even after adjustment. The adjusted difference between men and women decreased from 26.93 min in 2002 to -1.97 min for women in 2019. CONCLUSION: Over two decades, delay between symptom onset and hospital admission in STEMI decreased significantly for men and women. The decline was more pronounced in women, leading to the sex gap disappearing in the adjusted analysis for 2019.

Because the delay between onset of heart attack symptoms and hospital admission was higher in women in the past, this study analysed whether pre-hospital delay has shortened in general since 2002 as well as in women and men separately.Our study showed that the pre-hospital delay steadily decreased for both sexes but the decrease was greater in womenAfter considering differences in patient characteristics, such as higher age and less previous heart attacks in women, by 2019 the delay was nearly the same for women and men.