Factors associated with disease progression in patients with atrial fibrillation and heart failure anticoagulated with rivaroxaban.

BACKGROUND: Patients with atrial fibrillation (AF) and heart failure (HF) have a high risk of thromboembolism and other outcomes and anticoagulation is recommended. HYPOTHESIS: This study was aimed to explore the risk factors associated with HF worsening in patients with AF and HF taking rivaroxaban in Spain. METHODS: Multicenter, prospective, observational study that included adults with AF and chronic HF, receiving rivaroxaban ≥4 months before entering. HF worsening was defined as first hospitalization or emergency visit because of HF exacerbation. RESULTS: A total of 672 patients from 71 Spanish centers were recruited, of whom 658 (97.9%) were included in the safety analysis and 552 (82.1%) in the per protocol analysis. At baseline, mean age was 73.7 ± 10.9 years, 64.9% were male, CHA2 DS2 -VASc was 4.1 ± 1.5, HAS-BLED was 1.6 ± 0.9% and 51.3% had HF with preserved ejection fraction. After 24 months of follow-up, 24.9% of patients developed HF worsening, 11.6% died, 2.9% had a thromboembolic event, 3.1% a major bleeding, 0.5% an intracranial bleeding and no patient had a fatal hemorrhage. Older age, the history of chronic obstructive pulmonary disease, the previous use of vitamin K antagonists, and restrictive or infiltrative cardiomyopathies, were independently associated with HF worsening. Only 6.9% of patients permanently discontinued rivaroxaban treatment. CONCLUSIONS: Approximately one out of four patients with HF and AF treated with rivaroxaban developed a HF worsening episode after 2 years of follow-up. The identification of those factors that increase the risk of HF worsening could be helpful in the comprehensive management of this population.

Outcomes and factors associated with mortality in patients with atrial fibrillation and heart failure: FARAONIC study.

BACKGROUND: Heart failure (HF) and atrial fibrillation (AF) are common and coexistent conditions. HYPOTHESIS: To investigate the adverse events and mortality risk factors in patients with AF and HF treated with rivaroxaban in Spain. METHODS: Multicenter, prospective and observational study with a follow-up of 2 years, that included adults, with a diagnosis of nonvalvular AF and chronic HF, anticoagulated with rivaroxaban at least 4 months before being enrolled. RESULTS: A total of 672 patients from 71 Spanish centers were recruited, of whom 658 (97.9%) were included in the safety analysis and 552 (82.1%) in the per protocol analysis. At baseline, the mean age was 73.7 ± 10.9 years, 65.9% were male, 51.3% had HF with preserved ejection fraction and 58.7% were on New York Heart Association functional class II. CHA2 DS2 -VASc was 4.1 ± 1.5. During the follow-up, 11.6% of patients died and around one-quarter of patients were hospitalized or visited the emergency department, being HF worsening/progression the main cause (51.1%), with a 2.9% of thromboembolic events and 2.0% of acute coronary syndromes. Major bleeding occurred in 3.1% of patients, with 0.5% experiencing intracranial bleeding but no fatalities. Compliance with HF treatment was associated with a lower risk of death (hazard ratio: 0.092; 95% confidence interval: 0.03-0.31). CONCLUSIONS: Among patients with HF and AF anticoagulated with rivaroxaban, incidences of thromboembolic or hemorrhagic complications were low. The most important factor for improving survival was compliance with HF drugs, what strengths the need for early treatment with HF disease-modifying therapy and anticoagulation.

Adverse Clinical Outcomes and Associated Predictors in Rivaroxaban-Treated Atrial Fibrillation Patients With Renal Impairment.

Renal impairment confers worse prognosis in patients with atrial fibrillation (AF) but there is scarce evidence about the influence of direct-acting oral anticoagulants in routine clinical practice. Herein, we compared clinical outcomes between patients with AF with and without renal impairment on rivaroxaban and investigated predictors for clinical outcomes in patients with AF with renal impairment. This was a multicenter study including patients with AF on rivaroxaban for at least 6 months. During 2.5 years follow-up, ischemic strokes (IS)/transient ischemic attacks (TIA)/systemic embolisms (SE)/myocardial infarctions (MI), major bleeding, and major adverse cardiovascular events (MACE) were recorded. Creatinine clearance (CrCl) was estimated using the Cockroft-Gault equation, renal impairment was defined as a CrCl <60 ml/min, and 1,433 patients (34.8% with CrCl <60 ml/min) were included. Patients with CrCl <60 ml/min showed higher event rates for major bleeding (1.87%/year vs 0.62%/year; p = 0.003) and MACE (1.97%/year vs 0.62%/year; p = 0.002) but similar event rates for IS/TIA/SE/MI (0.66%/year vs 0.67%/year; p = 0.955). In patients with renal impairment, CHA2DS2-VASc was associated with higher risk of IS/TIA/SE/MI; HAS-BLED and any dependency level were associated with higher risk of major bleeding; and male gender and heart failure were associated with higher risk of MACE. Antiplatelets were independently associated with increased risk of IS/TIA/SE/MI and MACE. In conclusion, in patients with AF on rivaroxaban, the incidence of IS/TIA/SE/MI did not increase in those with renal impairment, suggesting that rivaroxaban may be an effective option in this subgroup. In patients with AF, male gender, heart failure, dependency, antiplatelets, CHA2DS2-VASc, and HAS-BLED were associated with increased risk of adverse outcomes.

Use of rivaroxaban attenuates renal function impairment in patients with atrial fibrillation: insights of the EMIR study.

BACKGROUND: In atrial fibrillation (AF) patients on vitamin K antagonists, a progressive deterioration of renal function is common but there is limited evidence with long-term use of rivaroxaban. Herein, we investigated the change in renal function in AF patients after 2 years of rivaroxaban treatment. METHODS: The EMIR registry is an observational and multicentre study including AF patients treated with rivaroxaban for at least 6 months prior to inclusion. Changes in analytical parameters were recorded during 2 years of follow-up. Renal function was estimated using the Cockroft-Gault equation. RESULTS: 1433 patients (638, 44.5% women, mean age of 74.2 ± 9.7 years) were included. Creatinine clearance (CrCl) was available at baseline and at 2 years in 1085 patients. At inclusion, 33.2% of patients had impaired renal function (CrCl <60 ml/min). At 2 years, we were not able to find changes in the proportion of patients with impaired renal function, which increased to 34.6% (p = 0.290). However, the baseline mean CrCl was 76.0 ± 30.5 ml/min and slightly improved at 2 years (77.0 ± 31.8 ml/min; p = 0.014). Overall, the proportion of patients with CrCl <60 ml/min at baseline that had CrCl ≥60 ml/min at 2 years was significantly higher compared to that of patients with CrCl ≥60 ml/min at baseline and CrCl <60 ml/min after (22.2% vs. 13.1%; p < 0.001) CONCLUSIONS: In AF patients on long-term rivaroxaban therapy, a decrease in renal function was not observed. We even observed a slight improvement in the patients with renal impairment. These results reinforce the idea that rivaroxaban may be a safe option even in patients with renal impairment.

Thromboembolic and bleeding events with rivaroxaban in clinical practice in Spain: impact of inappropriate doses (the EMIR study).

Aim: To analyze the frequency and variables related to inappropriate rivaroxaban dosage in clinical practice and its impact on outcomes after 2 years. Materials & methods: Postauthorization, observational, multicenter study, in which atrial fibrillation patients, treated with rivaroxaban ≥6 months were included. Results: A total of 1421 patients (74.2 ± 9.7 years, CHA2DS2-VASc 3.5 ± 1.6) were included. Overall, 22.9% received rivaroxaban 15 mg. The proper dose of rivaroxaban was taken by 83.3% (9.7% underdosed, 7.0% overdosed). Older age and renal insufficiency were associated with inadequate rivaroxaban dosage. There was a trend toward higher all-cause mortality among underdosed patients (adjusted hazard ratio 1.39; 95% CI 0.75-2.58), and more bleedings in overdosed patients (2.29 vs 0.80 events/100 patient-years; p = 0.14). Conclusion: In clinical practice, rivaroxaban is properly dosed in most patients.

Seguimiento de las recomendaciones del Informe de Posicionamiento Terapéutico sobre el tratamiento con anticoagulantes orales en pacientes ancianos con fibrilación auricular. Estudio ESPARTA / Adherence to recommendations of the Therapeutic Positioning Report about treatment with oral anticoagulants in elderly patients with atrial fibrillation. The ESPARTA study

Fundamento y objetivo: Evaluar en la práctica clínica el cumplimiento de las recomendaciones del Informe de Posicionamiento Terapéutico (IPT) de la Agencia Española de Medicamentos y Productos Sanitarios sobre el tratamiento con anticoagulantes orales en pacientes≥75 años con fibrilación auricular no valvular (FANV) atendidos en unidades de Medicina Interna en España. Pacientes y métodos: Estudio observacional, transversal y multicéntrico, en el que se incluyeron 837 pacientes≥75 años con FANV en tratamiento estable con anticoagulantes orales durante los 3 meses previos a la inclusión y que hubiesen iniciado dicho tratamiento antes de comenzar el período de inclusión. Resultados: La edad media fue de 83,0±5,0 años, el CHADS2 medio 3,2±1,2, el CHA2DS2-VASc 5,0±1,4 y el HAS-BLED 2,1±0,9. El 70,8% de los pacientes estaba en tratamiento con antagonistas de la vitamina K (AVK) y el resto con anticoagulantes orales de acción directa (ACOD). El 65,6% de los pacientes con AVK no siguieron las recomendaciones del IPT frente al 43,0% de los pacientes con ACOD (p<0,0001). En el caso de los pacientes con AVK, el motivo principal para ser considerado como no adecuado fue presentar un mal control de la anticoagulación y no cambiar a un ACOD, mientras que en el caso de los ACOD fue recibir una dosis inadecuada según el IPT. Conclusiones: En un porcentaje elevado de pacientes ancianos con FANV anticoagulados en España no se siguen las recomendaciones realizadas por el IPT, especialmente con los AVK, al no realizarse el cambio a ACOD a pesar de un tiempo en rango terapéutico inadecuado

Background and objective: To evaluate the adherence to the recommendations in clinical practice performed by the Therapeutic Positioning Report (TPR) of the Spanish Agency of Medicines and Sanitary Products about the treatment with oral anticoagulants in patients aged≥75 years old with nonvalvular atrial fibrillation (NVAF) treated in Internal Medicine departments in Spain. Patients and methods: Observational, cross-sectional and multicenter study in which 837 patients aged≥75 years old with NVAF, with stable treatment with oral anticoagulants at least 3 months before inclusion, and that had started treatment with oral anticoagulants before the inclusion period were included. Results: Mean age was 83.0±5.0 years old, mean CHADS2 score 3.2±1.2, mean CHA2DS2-VASc score 5.0±1.4, and mean HAS-BLED score 2.1±0.9. A percentage of 70.8 of patients were treated with vitamin K antagonists (VKA) and the rest of patients with direct oral anticoagulants (DOACs). A percentage of 65.6 of patients treated with VKA did not follow the recommendations made by the TPR compared with 43.0% of patients treated with DOACs (P<.0001). In the case of VKA, the main reason for being considered as not appropriate according to the TPR was having poor control of anticoagulation and not switching to DOACs, whereas in the case of DOACs, it was not receiving the adequate dose according to the TPR. Conclusions: In a high proportion of anticoagulated elderly patients with NVAF in Spain, the recommendations performed by the TPR are not followed, particularly with VKA, since patients are not switched to DOACs despite time in therapeutic range

Type and doses of oral anticoagulants and adherence to anticoagulant treatment in elderly patients with atrial fibrillation: the ESPARTA study.

AIM: To analyze the use of oral anticoagulants in elderly patients with atrial fibrillation in clinical practice. PATIENTS & METHODS: Cross-sectional and multicenter study performed in atrial fibrillation patients ≥75 years treated with oral anticoagulants ≥3 months. RESULTS: 837 patients (83.0 ± 5.0 years; CHA2DS2-VASc 5.0 ± 1.4; HAS-BLED 2.1 ± 0.9; 70.8% vitamin K antagonists; 29.2% direct oral anticoagulants [DOACs]) were included. Poor adherence was observed in 27.9% of patients. Higher scores in the Pfeiffer's test and FRAIL scale were associated with poorer adherence. Among patients treated with DOACs, 62.3% received the lower doses. Having high CHADS2 score and being older were associated with the use of low doses. CONCLUSION: 28% of patients had a poor adherence to anticoagulant treatment. 62% of patients were treated with the lower doses of DOACs.

Adherence to recommendations of the Therapeutic Positioning Report about treatment with oral anticoagulants in elderly patients with atrial fibrillation. The ESPARTA study. / Seguimiento de las recomendaciones del Informe de Posicionamiento Terapéutico sobre el tratamiento con anticoagulantes orales en pacientes ancianos con fibrilación auricular. Estudio ESPARTA.

BACKGROUND AND OBJECTIVE: To evaluate the adherence to the recommendations in clinical practice performed by the Therapeutic Positioning Report (TPR) of the Spanish Agency of Medicines and Sanitary Products about the treatment with oral anticoagulants in patients aged≥75 years old with nonvalvular atrial fibrillation (NVAF) treated in Internal Medicine departments in Spain. PATIENTS AND METHODS: Observational, cross-sectional and multicenter study in which 837 patients aged≥75 years old with NVAF, with stable treatment with oral anticoagulants at least 3 months before inclusion, and that had started treatment with oral anticoagulants before the inclusion period were included. RESULTS: Mean age was 83.0±5.0 years old, mean CHADS2 score 3.2±1.2, mean CHA2DS2-VASc score 5.0±1.4, and mean HAS-BLED score 2.1±0.9. A percentage of 70.8 of patients were treated with vitamin K antagonists (VKA) and the rest of patients with direct oral anticoagulants (DOACs). A percentage of 65.6 of patients treated with VKA did not follow the recommendations made by the TPR compared with 43.0% of patients treated with DOACs (P<.0001). In the case of VKA, the main reason for being considered as not appropriate according to the TPR was having poor control of anticoagulation and not switching to DOACs, whereas in the case of DOACs, it was not receiving the adequate dose according to the TPR. CONCLUSIONS: In a high proportion of anticoagulated elderly patients with NVAF in Spain, the recommendations performed by the TPR are not followed, particularly with VKA, since patients are not switched to DOACs despite time in therapeutic range.

Benefits of Emergency Departments' Contribution to Stroke Prophylaxis in Atrial Fibrillation: The EMERG-AF Study (Emergency Department Stroke Prophylaxis and Guidelines Implementation in Atrial Fibrillation).

BACKGROUND AND PURPOSE: Long-term benefits of initiating stroke prophylaxis in the emergency department (ED) are unknown. We analyzed the long-term safety and benefits of ED prescription of anticoagulation in atrial fibrillation patients. METHODS: Prospective, multicenter, observational cohort of consecutive atrial fibrillation patients was performed in 62 Spanish EDs. Clinical variables and thromboprophylaxis prescribed at discharge were collected at inclusion. Follow-up at 1 year post-discharge included data about thromboprophylaxis and its complications, major bleeding, and death; risk was assessed with univariate and bivariate logistic regression models. RESULTS: We enrolled 1162 patients, 1024 (88.1%) at high risk according to CHA2DS2-VASc score. At ED discharge, 935 patients (80.5%) were receiving anticoagulant therapy, de novo in 237 patients (55.2% of 429 not previously treated). At 1 year, 48 (4.1%) patients presented major bleeding events, and 151 (12.9%) had died. Anticoagulation first prescribed in the ED was not related to major bleeding (hazard ratio, 0.976; 95% confidence interval, 0.294-3.236) and was associated with a decrease in mortality (hazard ratio, 0.398; 95% confidence interval, 0.231-0.686). Adjusting by the main clinical and sociodemographic characteristics, concomitant antiplatelet treatment, or destination (discharge or admission) did not affect the results. CONCLUSIONS: Prescription of anticoagulation in the ED does not increase bleeding risk in atrial fibrillation patients at high risk of stroke and contributes to decreased mortality.

Validación del cuestionario de satisfacción ACTS en pacientes con fibrilación auricular tratados con anticoagulantes orales en España. Estudio ALADIN / Validation of satisfaction questionnaire ACTS in outpatients with atrial fibrillation treated with oral anticoagulants in Spain. ALADIN Study

Fundamento y objetivo: Validar el cuestionario de satisfacción Anti-Clot Treatment Scale (ACTS) en pacientes con fibrilación auricular no valvular (FANV) en tratamiento con anticoagulantes orales atendidos en consultas de Medicina Interna y Neurología de España. Métodos: Estudio transversal, multicéntrico, en el que se incluyeron 1.337 sujetos ≥ 18 años con FANV, en tratamiento con anticoagulantes orales ≥ 3 meses, atendidos en consultas de Medicina Interna o Neurología en España. Los pacientes completaron los cuestionarios ACTS, Self-Assessment of Treatment Questionnaire (SAT-Q) y EuroQol-5 dimensions (5Q-5D). La escala ACTS es un instrumento de satisfacción específico para la evaluación de la carga (mayor puntuación, menor carga) y beneficios (mayor puntuación, mayor beneficio) con el tratamiento anticoagulante. Se evaluaron las propiedades psicométricas del cuestionario de acuerdo con la teoría clásica de los test. Resultados: El tiempo medio en cumplimentar el cuestionario fue 8,99 ± 6,06min y el 63,70% de los pacientes precisaron ayuda para la cumplimentación del mismo. Existió una elevada concordancia entre las puntuaciones del test y el retest. La fiabilidad total (alfa de Cronbach) fue 0,95 en la escala Carga y 0,82 en la escala Beneficio. El modelo factorial resultó pertinente. Todas las correlaciones con el cuestionario SAT-Q fueron positivas, moderadas y estadísticamente significativas. Con respecto al cuestionario EQ-5D-3L, estas fueron positivas, bajas y estadísticamente significativas. La satisfacción de los pacientes fue mayor cuando estaban siendo tratados con anticoagulantes orales de acción directa. Conclusiones: En pacientes con FANV en tratamiento con anticoagulantes orales, la versión en español del cuestionario ACTS fue fiable, válida y factible (AU)

Background and objective: To validate the satisfaction questionnaire Anti-Clot-Treatment Scale (ACTS) in outpatients with nonvalvular atrial fibrillation (NVAF) treated with oral anticoagulants attended in Internal Medicine and Neurology departments in Spain. Methods: In this cross-sectional and multicentrer study, 1,337 outpatients aged ≥ 18 years, with NVAF, treated with oral anticoagulants ≥ 3 months, attended in Internal Medicine and Neurology departments in Spain were analyzed. The patients completed ACTS, Self-Assessment of Treatment Questionnaire (SAT-Q) and EuroQol-5 dimensions (EQ-5D) questionnaires. ACTS is a satisfaction tool that specifically analyzes burdens (higher score, lesser burden) and benefits (higher score, higher benefit) with anticoagulant treatment. The psychometric properties of the questionnaire were evaluated according to the classical test theory. Results: The average time to complete the questionnaire was 8.99 ± 6.06min and 63.70% of patients needed assistance to complete it. There was a high concordance between test and retest scores. Total reliability (Cronbach's alpha) was 0.95 in the ACTS Burdens scale and 0.82 in the ACTS Benefits scale. The factorial model was pertinent. All correlations with the SAT-Q questionnaire were positive, moderate and statistically significant. With regard to the EQ-5D-3L questionnaire, correlations were positive, low and statistically significant. Patient satisfaction was higher in the individuals being treated with new direct oral anticoagulants. Conclusions: In patients with NVAF treated with oral anticoagulants, the Spanish version of ACTS questionnaire was reliable, valid and feasible (AU)

[Validation of satisfaction questionnaire ACTS in outpatients with atrial fibrillation treated with oral anticoagulants in Spain. ALADIN Study]. / Validación del cuestionario de satisfacción ACTS en pacientes con fibrilación auricular tratados con anticoagulantes orales en España. Estudio ALADIN.

BACKGROUND AND OBJECTIVE: To validate the satisfaction questionnaire Anti-Clot-Treatment Scale (ACTS) in outpatients with nonvalvular atrial fibrillation (NVAF) treated with oral anticoagulants attended in Internal Medicine and Neurology departments in Spain. METHODS: In this cross-sectional and multicentrer study, 1,337 outpatients aged≥18 years, with NVAF, treated with oral anticoagulants≥3 months, attended in Internal Medicine and Neurology departments in Spain were analyzed. The patients completed ACTS, Self-Assessment of Treatment Questionnaire (SAT-Q) and EuroQol-5 dimensions (EQ-5D) questionnaires. ACTS is a satisfaction tool that specifically analyzes burdens (higher score, lesser burden) and benefits (higher score, higher benefit) with anticoagulant treatment. The psychometric properties of the questionnaire were evaluated according to the classical test theory. RESULTS: The average time to complete the questionnaire was 8.99±6.06min and 63.70% of patients needed assistance to complete it. There was a high concordance between test and retest scores. Total reliability (Cronbach's alpha) was 0.95 in the ACTS Burdens scale and 0.82 in the ACTS Benefits scale. The factorial model was pertinent. All correlations with the SAT-Q questionnaire were positive, moderate and statistically significant. With regard to the EQ-5D-3L questionnaire, correlations were positive, low and statistically significant. Patient satisfaction was higher in the individuals being treated with new direct oral anticoagulants. CONCLUSIONS: In patients with NVAF treated with oral anticoagulants, the Spanish version of ACTS questionnaire was reliable, valid and feasible.

New oral anticoagulants vs vitamin K antagonists: benefits for health-related quality of life in patients with atrial fibrillation.

New oral anticoagulants (NOAC) have demonstrated their efficacy as an alternative to vitamin K antagonists (VKA) in the prophylaxis of cardioembolic events in patients with atrial fibrillation (AF). However, evidence on the benefits of NOAC in health-related quality of life (HRQoL) is lacking.We evaluated changes in HRQoL related to oral anticoagulation therapy employing a specific questionnaire in a cohort of 416 patients with AF undergoing electrical cardioversion. In terms of HRQoL, we observed a progressive adaptation to treatment with VKA; satisfaction with NOAC remained constant. Older age, higher left ventricular ejection fraction and NOAC were associated with better HRQoL.