A comparison of front-line oral anticoagulants for the treatment of non-valvular atrial fibrillation: effectiveness and safety of direct oral anticoagulants in the FANTASIIA registry.

INTRODUCTION: For a long time, vitamin K antagonists (VKA) were the only oral anticoagulation therapy available to reduce adverse events in atrial fibrillation (AF) patients. Direct-acting oral anticoagulants (DOAC) are at least as effective and safe as VKA with few drug interactions, rapid onset, and short half-life. Four DOACs, dabigatran, apixaban, rivaroxaban, and edoxaban, have demonstrated efficacy and safety for treatment in AF patients. AREAS COVERED: The purpose of this review article is to analyze the current evidence in clinical trials and in real-world populations and performed a new analysis with the estimated effect of those DOACs over the VKA population from the FANTASIIA registry. EXPERT OPINION: In the absence of randomized, controlled head-to-head comparisons between DOACs, high-quality observational data can provide useful information on the comparative effectiveness of DOACs. Current clinical guidelines recommend the management of oral anticoagulation in AF patients with DOACs over VKA for stroke prevention; however, many guidelines generally do not suggest a specific DOAC choice in clinical practice. The revised evidence in this manuscript and our real experience reflects that apixaban and dabigatran show the best efficacy and safety profile.

Impact of Integrated Care Management on Clinical Outcomes in Atrial Fibrillation Patients: A Report From the FANTASIIA Registry.

Background: An integrated and holistic approach is increasingly advocated in patients with atrial fibrillation (AF), based on the "Atrial fibrillation Better Care (ABC) pathway: A, Avoid stroke with anticoagulation; B, better symptom management; C, cardiovascular and comorbidity risk management." The aim of this study was to examine the prevalence of adherence to each component of the ABC pathway and to analyze its impact on long-term prognosis in the "real-world" cohort of AF patients from the FANTASIIA registry. Methods: This prospective study included consecutive AF outpatients anticoagulated with direct oral anticoagulants (DOAC) or vitamin K antagonists (VKA) from June 2013 to October 2014. From the ABC pathway, adherence to the "A criterion" was defined by a time in the therapeutic range (TTR) ≥ 70% or correct dose with DOAC; "B criterion" adherence was defined by a European Heart Rhythm Association (EHRA) Symptom Scale I-II; and "C criterion" adherence was defined as optimized risk factors and comorbidity management. Baseline features and embolic events, severe bleeding, and all-cause and cardiovascular mortality rates up to 3 years of follow-up were analyzed, and a Cox multivariate analysis was performed to investigate the role of each component of the ABC pathway in predicting major events. Results: A total of 1,955 AF patients (age: 74.4 ± 9.4 years; 43.2% female patients) were included in this study: adherence to A criterion was observed in 920 (47.1%) patients; adherence to B criterion was observed in 1,791 (91.6%) patients; and adherence to C criterion was observed in 682 (34.8%) patients. Only 394 (20.2%) of the whole population had good control of AF according to the ABC pathway. After a median follow-up of 1,078 days (IQR: 766-1,113), adherence to A criterion was independently associated with reduced cardiovascular mortality [HR: 0.67, 95%CI (0.45-0.99); p = 0.048] compared with non-adherence. Adherence to the B criterion was independently associated with reduced stroke [HR: 0.28, 95%CI (0.14-0.59); p < 0.001], all-cause mortality [HR: 0.49, 95%CI (0.35-0.69); p < 0.001], cardiovascular mortality [HR: 0.39, 95%CI (0.25-0.62); p < 0.001], and major adverse cardiovascular events (MACE) [HR: 0.41, 95%CI (0.28-0.62); p < 0.001] compared with non-adherence. AF patients with C criterion adherence had a significantly lower risk of myocardial infarction [HR: 0.31, 95%CI (0.15-0.66); p < 0.001]. Fully adherent ABC patients had a significant reduction in MACE [HR: 0.64, 95%CI (0.42-0.99); p = 0.042]. Conclusion: In real-world anticoagulated AF patients from FANTASIIA registry, we observed a lack of adherence to integrated care management of AF following the ABC pathway. AF managed according to the ABC pathway was associated with a significant reduction in adverse outcomes during long follow-up, suggesting the benefit of a holistic and integrated approach to AF management.

Antithrombotic therapy and clinical outcomes at 1 year in the Spanish cohort of the EORP-AF Long-term General Registry.

BACKGROUND: Atrial fibrillation (AF) increases the risk of thromboembolism. We investigate the efficacy and safety of oral anticoagulation (OAC) therapy and explored the number needed to treat for net effect (NNTnet) of OAC in the Spanish cohort of the EURObservational Research Programme-AF (EORP-AF) Long-term General Registry. METHODS: The EORP-AF General Registry is a prospective, multicentre registry conducted in ESC countries, including consecutive AF patients. For the present analysis, we used the Spanish cohort, and the primary outcome was any thromboembolism (TE)/acute coronary syndrome (ACS)/cardiovascular death during the first year of follow-up. RESULTS: 729 AF patients were included (57.1% male, median age 75 [IQR 67-81] years, median CHA2 DS2 -VASc and HAS-BLED of 3 [IQR 2-5] and 2 [IQR 1-2], respectively). 548 (75.2%) patients received OAC alone (318 [43.6%] on VKAs and 230 [31.6%] on DOACs). After 1 year, the use of OAC alone showed lower rates of any TE/ACS/cardiovascular death (3.0%/year; p < 0.001) compared to other regimens, and non-use of OAC alone (HR 4.18, 95% CI 2.12-8.27) was independently associated with any TE/ACS/cardiovascular death. Balancing the effects of treatment, the NNTnet to provide an overall benefit of OAC therapy was 24. The proportion of patients on OAC increased at 1 year (87% to 88.1%), particularly on DOACs (33.6% to 39.9%) (p = 0.015), with low discontinuation rates. CONCLUSIONS: In this contemporary cohort of AF patients, OAC therapy was associated with better clinical outcomes at 1 year and positive NNTnet. OAC use slightly increased during the follow-up, with low discontinuation rates and higher prescription of DOACs.

Characterization of atrial fibrillation in real-world patients: testing the 4S-AF scheme in the Spanish and French cohorts of the EORP-AF Long-Term General Registry.

AIMS: The 4S-AF scheme [Stroke risk, Symptom severity, Severity of atrial fibrillation (AF) burden, Substrate severity] has recently been described as a novel approach to in-depth characterization of AF. We aim to determine if the 4S-AF scheme would be useful for AF characterization and provides prognostic information in real-world AF patients. METHODS AND RESULTS: The Spanish and French cohorts of the EORP-AF Long-Term General Registry were included. The baseline 4S-AF scheme was calculated and related to the primary management strategy (rhythm or rate control). Follow-up was performed at 1-year with all-cause mortality and the composite of ischaemic stroke/transient ischaemic attack/systemic embolism, major bleeding, and all-cause death, as primary endpoints. A total of 1479 patients [36.9% females, median age 72 interquartile range (IQR 64-80) years] were included. The median 4S-AF scheme score was 5 (IQR 4-7). The 4S-AF scheme, as continuous and as categorical, was associated with the management strategy decided for the patient (both P < 0.001). The predictive performances of the 4S-AF scheme for the actual management strategy were appropriate in its continuous [c-index 0.77, 95% confidence interval (CI) 0.75-0.80] and categorical (c-index 0.75, 95% CI 0.72-0.78) forms. Cox regression analyses showed that 'red category' classified patients in the 4S-AF scheme had a higher risk of all-cause death (aHR 1.75, 95% CI 1.02-2.99) and composite outcomes (aHR 1.60, 95% CI 1.05-2.44). CONCLUSION: Characterization of AF by using the 4S-AF scheme may aid in identifying AF patients that would be managed by rhythm or rate control and could also help in identifying high-risk AF patients for worse clinical outcomes in a 'real-world' setting.

Epidemiology of atrial fibrillation-related ischemic stroke and its association with DOAC uptake in Spain: first national population-based study 2005 to 2018.

INTRODUCTION AND OBJECTIVES: The incidence and prevalence of atrial fibrillation (AF), a major risk factor for stroke, has increased substantially in the past few years. However, several studies have reported a decline in AF-related stroke rates associated with higher uptake of direct oral anticoagulants (DOACs). This ecological study evaluated the association between DOAC uptake in Spain and the incidence rate (IR) of AF-related ischemic stroke. METHODS: Data were obtained from the Registry of Activity of Specialized Healthcare of the Spanish Ministry of Health (RAE-MDS). AF-related ischemic strokes were identified using International Classification of Diseases codes. IR were age-standardized and adjusted to the 2013 European standard population. Poisson regression models were used to identify the association between DOAC uptake and AF-related ischemic stroke in patients aged ≥ 65 years. RESULTS: Before the use of DOACs, the adjusted IR of AF-related ischemic stroke increased steadily from 2005 (IR=2.20 per 100 000 person/y) to 2012 (IR=2.67). Upon DOAC uptake in Spain from 2012 onwards for AF-related ischemic stroke prevention, the IR remained constant or decreased slightly (IR in 2018=2.66). Poisson regression showed that DOAC uptake was a significant predictor for the rate of AF-related ischemic stroke in patients older than 65 years (IRR=0.995; 95%CI, 0.995-0.996). CONCLUSIONS: This study shows an association between DOAC use and a reduced incidence of AF-related ischemic stroke. While this association is based on aggregate data and cannot demonstrate causality, these findings suggest that higher DOAC uptake could improve health outcomes in AF patients in Spain.

Relationship between multimorbidity and outcomes in atrial fibrillation.

BACKGROUND: Multimorbidity is common in atrial fibrillation (AF) patients. Charlson comorbidity index (CCI) is used to evaluate multimorbidity in the general population. Limited long-term data are available on the relationship between CCI and AF. We examined the association between CCI, anticoagulation control and outcomes in AF patients. METHODS: We studied 1956 from the FANTASIIA registry, an observational Spanish nationwide study on anticoagulated AF patients. Time in therapeutic range (TTR) was used to evaluate anticoagulation control. Stroke/TIA, major bleeding, cardiovascular (CV) death and all-cause death were study outcomes. RESULTS: Mean ± SD CCI was 1.1 ± 1.2. Based on CCI quartiles, patients were categorised in four groups: 676 (34.6%) in Q1 (CCI 0); 683 (34.9%) in Q2 (CCI 1); 345 (17.6%) in Q3 (CCI 2); and 252 (12.9%) in Q4 (CCI ≥3). In vitamin K antagonist treated patients, the highest CCI quartile was inversely associated with TTR >70% (odds ratio:0.67, 95% confidence interval (CI):0.45-0.99). During observation, a progressively higher rate of major bleeding, CV death and all-cause death was found across the quartiles (all p < 0.001). The final Cox multivariable regression analysis showed an association with increasing risk for major bleeding occurrence in Q3 and Q4 (hazard ratio (HR):1.69, 95%CI:1.00-2.87 and HR:1.92, 95%CI:1.08-3.41). An increasing risk for all-cause death and CV death was found across CCI quartiles. CONCLUSIONS: In a nationwide contemporary cohort of AF anticoagulated patients, multimorbidity was inversely associated with good anticoagulation control. A progressively higher risk for major bleeding, CV death and all-cause death was found across CCI quartiles.

Peripheral artery disease and clinical outcomes in patients with atrial fibrillation: A report from the FANTASIIA registry.

BACKGROUND: Atrial fibrillation (AF) and peripheral artery disease (PAD) are common conditions that increase cardiovascular risk. We determined the association between PAD and prognosis in a cohort of real-world patients receiving oral anticoagulant therapy for nonvalvular AF. METHODS: We prospectively included 1956 patients (mean age 73.8 ± 9.5 years, 44.0% women) receiving oral anticoagulant therapy for AF. Clinical characteristics were collected at baseline. Patients were followed for a period of 3 years. Survival analysis and multivariable regression analyses were performed to assess variables related to death, stroke, bleeding, myocardial infarction and major adverse cardiovascular events (MACE). RESULTS: Patients with PAD (n = 118; 6%) exhibited higher rates of cardiovascular risk factors and cardiovascular diseases. After 3 years of follow-up, there were a total of 255 deaths (no PAD 233, vs PAD 22), 45 strokes (43 vs 2), 146 major bleedings (136 vs 10) and 168 MACE (148 vs 20). On univariate analysis, there was a higher risk of cardiovascular mortality (2.02%/year no PAD vs 4.08%/year PAD, P = .02), myocardial infarction (0.99%/year no PAD vs 2.43%/year PAD, P = .02) and MACE (3.18%/year no PAD vs 6.99%/year PAD, P < .01). There was no statistically significant association with these events after multivariable adjustment. CONCLUSIONS: In a large cohort of anticoagulated patients with AF, the presence of PAD represents a higher risk subgroup and is associated with worse crude outcomes. The exact contribution of the PAD independently of other cardiovascular diseases or risk factors requires further investigation.

Relationship of adverse events to quality of anticoagulation control in atrial fibrillation patients with diabetes: real-world data from the FANTASIIA Registry.

BACKGROUND: Atrial fibrillation (AF) patients with diabetes (DM) have high risk of cardiovascular events. PURPOSE: To compare clinical characteristics, adverse outcomes and quality of anticoagulation in AF patients regarding DM status. METHODS: AF patients from FANTASIIA registry were included. Baseline characteristics and comorbidities were recorded. After 2-years follow-up, the association between adverse events and DM was evaluated. RESULTS: 1956 patients (mean age 73.8 ± 9.5 years, 56% male) were analyzed; 574 (29.3%) had DM. Diabetic patients had also high prevalence of hypertension (90.6% vs 76.1%; p < .001) or renal disease (21.4% vs 15.9%; p < .001). After median follow-up of 1077 days (IQR 766-1113 days), diabetic patients had high total mortality (16.9%/year vs 11.4%/year; p < .001), cardiovascular mortality (9.1%/year vs 3.9%/year; p < .001) and MACE (12.9%/year vs 6.8%/year; p < .001). DM patients had poor anticoagulation control (time in therapeutic range: 58.52 ± 24.37% vs 62.68 ± 25.31%; p = .002). DM with lower TTR showed higher cardiovascular death and MACE. Multivariate analysis showed an independent association between DM and cardiovascular mortality [HR 1.73 (IC95% 1.07-2.80); p = .024]. CONCLUSION: AF Diabetic patients have higher comorbidities and poorer TTR than nondiabetic patients. Low TTR was associated with adverse events. The risk of cardiovascular outcomes was higher in DM patients, with independent association between DM and mortality risk.

Influence of sex on long-term prognosis in patients with atrial fibrillation treated with oral anticoagulants. Results from the prospective, nationwide FANTASIIA study.

BACKGROUND: While many risk factors for Atrial Fibrillation (AF) have been identified, there are important differences in their relative impact between sexes. The aim of our study was to investigate the influence of sex as a long-term predictor of adverse events in "real world" AF patients treated with direct oral anticoagulants. METHODS: The FANTASIIA registry is a prospective, national and multicentric study including outpatients with anticoagulated AF patients. Baseline characteristics and adverse events at 3 years of follow-up were collected and classified by sex. Cox multivariate analysis was performed to investigate the role of sex in major events and composite outcomes. RESULTS: A total of 1956 patients were included in the study. 43.9% of them were women, with a mean age of 73.8 ± 9.4 years (women were older 76.5 ± 7.9 vs 71.7 ± 10.1, p<0.001). Women had higher rate of cardiovascular risk factors and higher mean of CHA2DS2-VASc (4.4 ± 1.4 vs 3.7 ± 1.6, p<0.001) and HAS-BLED (2.1 ± 1.0 vs 1.9 ± 1.1, p<0.001) than men. After 3 years of follow-up, rates of major events were similar in both groups with limit difference for all-cause mortality (4.4%/year in women vs 5.6%/year in men; p = 0.056). However, all the composite events were more frequent in women. We observed in the non-adjusted adverse events lower rate of all-cause mortality (HR 0.62, 95%CI 0.47-0.81; p<0.001), composite 1 outcomes (HR 0.80, 95%CI 0.65-0.98; p = 0.029) and composite 2 (HR 0.77, 95%CI 0.64-0.94; p = 0.010) in women compared with men. In multivariate Cox regression analysis observed that female sex was an independently protector factor for all-cause mortality and for the composite outcomes 1 and 2. CONCLUSIONS: In this "real world" study of anticoagulated AF patients, women could have a protective role against development of adverse events, mainly on all-cause mortality and combined events.

Use of edoxaban in clinical practice: Comparison of data from the Spanish population in the ETNA-AF-Europe registry.

Aim: To ascertain the clinical profile and management of edoxaban in clinical practice. Materials & methods: Prospective, noninterventional postauthorization study of nonselected patients with atrial fibrillation treated with edoxaban from 12 European countries. Patients' baseline characteristics are presented. Results: A total of 13,638 patients (73.6 ± 9.5 years; 76.6/23.4% edoxaban 60/30 mg; CHA2DS2-VASc 3.1; 838 [6.1%] from Spain) were included. In Spain, the percentage of very elderly and fragile patients was greater and the risk of thromboembolism (CHA2DS2-VASc ≥2, 98.0 vs 87.3%; p < 0.001) and bleeding (HAS-BLED, 3.2 vs 2.7; p < 0.001) was greater in patients treated with edoxaban 30 mg. The proportion of patients taking edoxaban 30 mg was similar than in ENGAGE AF-TIMI 48. Conclusion: In Spain, patients treated with edoxaban were older and fragile.

Anticoagulantes orales directos frente a antagonistas de la vitamina K en pacientes del «mundo real» con fibrilación auricular no valvular. Estudio FANTASIIA / Direct oral anticoagulants versus vitamin K antagonists in real-world patients with nonvalvular atrial fibrillation. The FANTASIIA study

INTRODUCCIÓN Y OBJETIVOS: Comparar los resultados a largo plazo de los anticoagulantes orales directos (ACOD) frente a los antagonistas de la vitamina K (AVK) en pacientes del mundo real con fibrilación auricular no valvular (FANV) en un estudio nacional prospectivo. MÉTODOS: El estudio FANTASIIA incluyó consecutivamente a pacientes ambulatorios con FANV anticoagulados con ACOD o AVK desde junio de 2013 hasta octubre de 2014. Se compararon las tasas de eventos según el anticoagulante administrado. RESULTADOS: Se incluyó a 2.178 pacientes (edad, 73,8+/-9,4 años; el 43,8% mujeres); de ellos, 533 (24,5%) recibían ACOD y 1.645 (75,5%), AVK. Tras una mediana de seguimiento de 32,4 meses, los pacientes con ACOD tuvieron tasas más bajas de ictus -0,40 (IC95%, 0,17-0,97) frente a 1,07 (IC95%, 0,79-1,46) pacientes/año; p = 0,032-, hemorragias mayores -2,13 (IC95%, 1,45-3,13) frente a 3,28 (IC95%, 2,75-3,93) pacientes/año; p = 0,044-, muerte cardiovascular -1,20 (IC95%, 0,72-1,99) frente a 2,45 (IC95%, 2,00-3,00) pacientes/año; p = 0,009- y muerte total -3,77 (IC95%, 2,83-5,01) frente a 5,54 (IC95%, 4,83-6,34) pacientes/año; p = 0,016-. En el análisis de Cox modificado según el método de Andersen-Gill para datos con múltiples eventos, las razones de riesgos instantáneos para los pacientes con ACOD fueron 0,42 (0,16-1,07) para el ictus; 0,47 (0,20-1,16) para la embolia sistémica en general; 0,76 (0,50-1,15) para las hemorragias mayores; 0,67 (0,39-1,18) para la muerte cardiovascular; 0,86 (0,62-1,19) para la mortalidad total y 0,82 (0,64-1,05) para el combinado de ictus, embolias, hemorragias mayores y muerte. CONCLUSIONES: El tratamiento con ACOD se asocia con una tendencia a una menor tasa de todos los eventos graves, incluida la mortalidad, en relación con los AVK en pacientes con FANV en España

INTRODUCTION AND OBJECTIVES: To compare the long-term results of direct oral anticoagulants (DOAC) vs vitamin K antagonists (VKA) in real-world-patients with nonvalvular atrial fibrillation (NVAF) in a nationwide, prospective study. METHODS: The FANTASIIA registry prospectively included outpatients with AF anticoagulated with DOAC or VKA (per protocol, proportion of VKA and DOAC 4:1), consecutively recruited from June 2013 to October 2014 in Spain. The incidence of major events was analyzed and compared according to the anticoagulant treatment received. RESULTS: A total of 2178 patients were included in the study (mean age 73.8+/-9.4 years), and 43.8% were women. Of these, 533 (24.5%) received DOAC and 1645 (75.5%) VKA. After a median follow up of 32.4 months, patients receiving DOAC vs those receiving VKA had lower rates of stroke-0.40 (95%CI, 0.17-0.97) vs 1.07 (95%CI,0.79-1.46) patients/y, P=.032-, severe bleedings-2.13 (95%CI, 1.45-3.13) vs 3.28 (95%CI, 2.75-3.93) patients/y; P = .044-, cardiovascular death-1.20 (95%CI, 0.72-1.99) vs 2.45 (95%CI, 2.00-3.00) patients/y; P = .009-, and all-cause death-3.77 (95%CI, 2.83-5.01) vs 5.54 (95%CI, 4.83-6.34) patients/y; P = .016-. In a modified Cox regression model by the Andersen-Gill method for multiple events, hazard ratios for patients receiving DOAC were: 0.42 (0.16-1.07) for stroke; 0.47 (0.20-1.16) for total embolisms; 0.76 (0.50-1.15) for severe bleedings; 0.67 (0.39-1.18) for cardiovascular death; 0.86 (0.62-1.19) for all-cause death, and 0.82 (0.64-1.05) for the combined event consisting of stroke, embolism, severe bleeding, and all-cause death. CONCLUSIONS: Compared with VKA, DOAC is associated with a trend to a lower incidence of all major events, including death, in patients with NVAF in Spain

Direct oral anticoagulants versus vitamin K antagonists in real-world patients with nonvalvular atrial fibrillation. The FANTASIIA study.

INTRODUCTION AND OBJECTIVES: To compare the long-term results of direct oral anticoagulants (DOAC) vs vitamin K antagonists (VKA) in real-world-patients with nonvalvular atrial fibrillation (NVAF) in a nationwide, prospective study. METHODS: The FANTASIIA registry prospectively included outpatients with AF anticoagulated with DOAC or VKA (per protocol, proportion of VKA and DOAC 4:1), consecutively recruited from June 2013 to October 2014 in Spain. The incidence of major events was analyzed and compared according to the anticoagulant treatment received. RESULTS: A total of 2178 patients were included in the study (mean age 73.8±9.4 years), and 43.8% were women. Of these, 533 (24.5%) received DOAC and 1645 (75.5%) VKA. After a median follow up of 32.4 months, patients receiving DOAC vs those receiving VKA had lower rates of stroke-0.40 (95%CI, 0.17-0.97) vs 1.07 (95%CI,0.79-1.46) patients/y, P=.032-, severe bleedings-2.13 (95%CI, 1.45-3.13) vs 3.28 (95%CI, 2.75-3.93) patients/y; P = .044-, cardiovascular death-1.20 (95%CI, 0.72-1.99) vs 2.45 (95%CI, 2.00-3.00) patients/y; P = .009-, and all-cause death-3.77 (95%CI, 2.83-5.01) vs 5.54 (95%CI, 4.83-6.34) patients/y; P = .016-. In a modified Cox regression model by the Andersen-Gill method for multiple events, hazard ratios for patients receiving DOAC were: 0.42 (0.16-1.07) for stroke; 0.47 (0.20-1.16) for total embolisms; 0.76 (0.50-1.15) for severe bleedings; 0.67 (0.39-1.18) for cardiovascular death; 0.86 (0.62-1.19) for all-cause death, and 0.82 (0.64-1.05) for the combined event consisting of stroke, embolism, severe bleeding, and all-cause death. CONCLUSIONS: Compared with VKA, DOAC is associated with a trend to a lower incidence of all major events, including death, in patients with NVAF in Spain.

Association of Body Mass Index With Clinical Outcomes in Patients With Atrial Fibrillation: A Report From the FANTASIIA Registry.

Background Obesity and atrial fibrillation (AF) frequently coexist and independently increase mortality. We sought to assess the association between obesity and adverse events in patients receiving oral anticoagulants for AF. Methods and Results Consecutive AF outpatients receiving anticoagulant agents (both vitamin K antagonists and direct oral anticoagulants) were recruited into the FANTASIIA (Atrial fibrillation: influence of the level and type of anticoagulation on the incidence of ischemic and hemorrhagic stroke) registry. This observational, multicenter, and prospective registry of AF patients analyzes the quality of anticoagulation, incidence of events, and differences between oral anticoagulant therapies. We analyzed baseline patient characteristics according to body mass index, normal: <25 kg/m2, overweight: 25-30 kg/m2, and obese: ≥30 kg/m2), assessing all-cause mortality, stroke, major bleeding and major adverse cardiovascular events (a composite of ischemic stroke, myocardial infarction, and total mortality) at 3 years' follow-up. In this secondary prespecified substudy, the association of weight on prognosis was evaluated. We recruited 1956 patients (56% men, mean age 73.8±9.4 years): 358 (18.3%) had normal body mass index, 871 (44.5%) were overweight, and 727 (37.2%) were obese. Obese patients were younger (P<0.01) and had more comorbidities. Mean time in the therapeutic range was similar across body mass index categories (P=0.42). After a median follow-up of 1070 days, 255 patients died (13%), 45 had a stroke (2.3%), 146 a major bleeding episode (7.5%) and 168 a major adverse cardiovascular event (8.6%). Event rates were similar between groups for total mortality (P=0.29), stroke (P=0.90), major bleeding (P=0.31), and major adverse cardiovascular events (P=0.24). On multivariate Cox analysis, body mass index was not independently associated with all-cause mortality, cardiovascular mortality, stroke, major bleeding, or major adverse cardiovascular events. Conclusions In this prospective cohort of patients anticoagulated for AF, obesity was highly prevalent and was associated with more comorbidities, but not with poor prognosis.

Perfil de seguridad de los anticoagulantes directos. Uso preferente en fibrilación auricular / Security profile of direct anticoagulants. Preferred use in atrial fibrillation

Se presenta un trabajo multidisciplinar realizado por especialistas de Cardiología, Hemostasia y Trombosis, Medicina Interna y Neurología en el que se exponen las evidencias científicas actuales que demuestran el mejor perfil de seguridad de los anticoagulantes orales de acción directa (ACOD) frente a los antivitamina K (AVK) y se discuten indicaciones y el papel de los antídotos específicos y hemostáticos para la reversión del efecto anticoagulante. El análisis sugiere que el mejor perfil de seguridad de los ACOD los hace especialmente útiles en pacientes con alto riesgo hemorrágico

A multidisciplinary panel of cardiologists, neurologists, internal medicine and specialists in hemostasis and thrombosis has elaborated this document showing recent scientific evidences supporting a better profile of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKA), as well as the indications of specific antidotes and hemostatic agents to reverse the anticoagulant effects of DOACs. The analysis reinforces the best profile of DOACs and its special benefit in patients with basal high hemorrhagic risk

Abordaje de la fibrilación auricular en pacientes con cáncer activo. Documento de consenso de expertos y recomendaciones / Atrial fibrillation in active cancer patients: expert position paper and recommendations

La mejora en la supervivencia de los pacientes con cáncer ha puesto de manifiesto el impacto clínico que la cardiotoxicidad tiene en el pronóstico tanto cardiovascular como onco-hematológico, sobre todo cuando motiva la interrupción de terapias antitumorales altamente eficaces. La fibrilación auricular es una complicación frecuente en pacientes con cáncer activo y su tratamiento supone un gran reto. Estos pacientes tienen mayores riesgos tromboembólico y hemorrágico y, sin embargo, no se dispone de escalas específicas para guiar la atención clínica. El objetivo de este documento promovido por los grupos de Cardio-Onco-Hematología y Trombosis de la Sociedad Española de Cardiología y elaborado de manera conjunta con las diferentes áreas de conocimiento de la Sociedad Española de Cardiología y con expertos de la Sociedad Española de Oncología Médica, la Sociedad Española de Oncología Radioterápica y la Sociedad Española de Hematología y Hemoterapia, es proporcionar un enfoque multidisciplinario y práctico para la prevención y el tratamiento de la fibrilación auricular de pacientes con cáncer activo y basado en el consenso de expertos

Improvements in survival among cancer patients have revealed the clinical impact of cardiotoxicity on both cardiovascular and hematological and oncological outcomes, especially when it leads to the interruption of highly effective antitumor therapies. Atrial fibrillation is a common complication in patients with active cancer and its treatment poses a major challenge. These patients have an increased thromboembolic and hemorrhagic risk but standard stroke prediction scores have not been validated in this population. The aim of this expert consensus-based document is to provide a multidisciplinary and practical approach to the prevention and treatment of atrial fibrillation in patients with active cancer. This is a position paper of the Spanish Cardio-Oncology working group and the Spanish Thrombosis working group, drafted in collaboration with experts from the Spanish Society of Cardiology, the Spanish Society of Medical Oncology, the Spanish Society of Radiation Oncology, and the Spanish Society of Hematology

Atrial Fibrillation in Active Cancer Patients: Expert Position Paper and Recommendations.

Improvements in survival among cancer patients have revealed the clinical impact of cardiotoxicity on both cardiovascular and hematological and oncological outcomes, especially when it leads to the interruption of highly effective antitumor therapies. Atrial fibrillation is a common complication in patients with active cancer and its treatment poses a major challenge. These patients have an increased thromboembolic and hemorrhagic risk but standard stroke prediction scores have not been validated in this population. The aim of this expert consensus-based document is to provide a multidisciplinary and practical approach to the prevention and treatment of atrial fibrillation in patients with active cancer. This is a position paper of the Spanish Cardio-Oncology working group and the Spanish Thrombosis working group, drafted in collaboration with experts from the Spanish Society of Cardiology, the Spanish Society of Medical Oncology, the Spanish Society of Radiation Oncology, and the Spanish Society of Hematology.

Security profile of direct anticoagulants. Preferred use in atrial fibrillation. / Perfil de seguridad de los anticoagulantes directos. Uso preferente en fibrilación auricular.

A multidisciplinary panel of cardiologists, neurologists, internal medicine and specialists in hemostasis and thrombosis has elaborated this document showing recent scientific evidences supporting a better profile of direct oral anticoagulants (DOACs) versus vitaminK antagonists (VKA), as well as the indications of specific antidotes and hemostatic agents to reverse the anticoagulant effects of DOACs. The analysis reinforces the best profile of DOACs and its special benefit in patients with basal high hemorrhagic risk.

Relation of quality of anticoagulation control with different management systems among patients with atrial fibrillation: Data from FANTASIIA Registry.

BACKGROUND: Anticoagulation control in patients with atrial fibrillation (AF) has a multidisciplinary approach although is usually managed by general practitioners (GP) or haematologists. The aim of our study was to assess the quality of anticoagulation control with vitamin K antagonists (VKAs) in relation to the responsible specialist in a "real-world" AF population. METHODS: We consecutively enrolled VKA anticoagulated patients included in the FANTASIIA Registry from 2013 to 2015. We analysed demographical, clinical characteristics and the quality of anticoagulation control according to the specialist responsible (ie GPs or haematologists). RESULTS: Data on 1584 patients were included (42.5% females, mean age 74.0 ± 9.4 years): 977 (61.7%) patients were controlled by GPs and 607 (38.3%) by haematologists. Patients managed by GPs had higher previous heart disease (53.2% vs 43.3%, P < .001), heart failure (32.9% vs 26.5%, P < .008) and dilated cardiomyopathy (15.2% vs 8.7%, P < .001) with better renal function (69.3 ± 24.7 vs 63.1 ± 21.4 mL/min, P < .001) compared to patients managed by haematologists. There was no difference between groups in the type of AF, CHA2 DS2 -VASc or HAS-BLED scores, but patients with electrical cardioversion were more prevalent in GP group. The overall mean time in therapeutic range (TTR) assessed by Rosendaal method was 61.5 ± 24.9%; 52.6% of patients had TTR<65% and 60% of patients had TTR<70%. TTR was significantly lower in patients controlled by haematologists than by GPs (63 ± 24.4 vs 59.2 ± 25.6, P < .005). CONCLUSIONS: About 60% of AF patients anticoagulated with VKAs had poor anticoagulation control (ie TTR<70%), and their management was only slightly better than when it is managed by general practitioners.

Relation of Renal Dysfunction to Quality of Anticoagulation Control in Patients with Atrial Fibrillation: The FANTASIIA Registry.

BACKGROUND: One-third of atrial fibrillation (AF) patients have chronic kidney disease (CKD), a condition that itself increases thromboembolic and major bleeding risks, especially in patients with severe CKD. Bleeding would be accentuated by suboptimal anticoagulation control with vitamin K antagonists (VKA). PURPOSE: This article aimed to investigate the incidence of cardiovascular events, mortality and quality of anticoagulation in relation to CKD in a 'real-world' prospective cohort of AF patients included in the FANTASIIA registry. METHODS: We analysed consecutive AF patients who were prospectively recruited with a year of follow-up. The quality of anticoagulation was estimated by time in therapeutic range (TTR). The annual incidence of events was analysed. RESULTS: We studied 1,936 patients (male: 55.7%, mean: 73.8 ± 9.4 years): 445 (22.9%) had normal function, 698 (36.1%) had mild CKD, 713 (36.8%) had moderate CKD and 80 (4.2%) had severe CKD. Patients with estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 (severe CKD) had lower TTR (53.3 ± 25.6% vs. 61.8 ± 25.1%, p = 0.007) and higher proportion of poor TTR (67.2 vs. 51.8%; p = 0.014) than patients with eGFR ≥30 mL/min/1.73 m2. Severe CKD was significantly associated with cardiovascular mortality (hazard ratio [HR]: 9.33; p = 0.002), major bleeding (HR: 2.94; p = 0.036) and major adverse cardiovascular events (MACE) (HR: 4.93; p = 0.004). Importantly, 375 patients (21.1%) showed a deteriorating eGFR of ≥10 mL/min during the follow-up, with significantly higher mortality and cardiovascular events. CONCLUSION: In a prospective and real-world AF registry, approximately 67% of patients with severe CKD had poor anticoagulation control while taking VKA. The presence of severe CKD was an independent factor for cardiovascular mortality, MACE and major bleeding. Worsening eGFR of only ≥10 mL/min during follow-up was significantly associated with mortality and major bleeding.

Quality of oral anticoagulation with vitamin K antagonists in 'real-world' patients with atrial fibrillation: a report from the prospective multicentre FANTASIIA registry.

Aims: The efficacy and safety of oral anticoagulation (OAC) using the vitamin K antagonists (VKA) are closely associated with the quality of anticoagulation, reflected by time in therapeutic range (TTR). The SAMe-TT2R2 is a risk score developed to predict the quality of anticoagulation control among VKA users. To analyse the quality of anticoagulation and its clinical determinants based on different methods in a prospective cohort of atrial fibrillation patients on VKA treatment participating in the multicentre Spanish observational registry FANTASIIA. Methods and results: Estimated TTR was calculated from Rosendaal, direct method, international normalized ratio variability, and NICE criteria. Time in therapeutic range values were compared for those patients with a SAMe-TT2R2 score 0-2 and >2. One thousand four hundred and seventy patients were analysed (56.4% male, mean age 74.1 ± 9.5 years). Mean TTR was 61.5 ± 25.1 with Rosendaal and 64.7 ± 24.2 with direct method. There was a high correlation between both methods (ρ = 0.805). The prevalence of poor anticoagulation control was 55%. Diabetes mellitus [odds ratio (OR) 1.38; P = 0.008], peripheral artery disease (PAD, OR 1.62; P = 0.048), and HAS-BLED (OR 1.13; P = 0.022) were independently associated with TTR < 70%. SAMe-TT2R2 score 0-2 had a higher mean TTR than patients with SAMe-TT2R2 >2 (P = 0.044), with a specificity of > 90% for predicting TTR < 70%. Patients with TTR < 70% had higher risk of events (21.7 vs. 16.8%; P = 0.021). Conclusion: In a multicentre prospective registry, 55% of AF patients had poor anticoagulation control with diabetes mellitus, PAD, and HAS-BLED being independently associated with TTR < 70%. A high SAMe-TT2R2 scores had a high specificity for predicting a TTR < 70% as an indicator of poor quality anticoagulation.