Clinical Characteristics, Patterns of Use, and incidence of Adverse Events in Patients With Nonvalvular Atrial Fibrillation Treated With Oral Anticoagulants in Colombia.

Purpose: The aim was to analyze the characteristics, treatment patterns, and clinical outcomes of Colombian patients with non-valvular atrial fibrillation (NVAF) under treatment with oral anticoagulants (OAs). Patients and Methods: Retrospective cohort in patients with NVAF identified from a drug dispensing database, aged ≥18 years, with first prescription of an OA (index) between January/2013 and June/2018, and a follow-up until June/2019. Data from the clinical history, pharmacological variables, and outcomes were searched. International Classification of Diseases-10 codes were used to identify the patient sample and outcomes. Patients were followed until a general composite outcome of effectiveness (thrombotic events), bleeding/safety or persistence (switch/discontinuation of anticoagulant) events. Descriptive and multivariate analyzes (Cox regressions comparing warfarin and direct oral anticoagulants-DOACs) were carried out. Results: A total of 2076 patients with NVAF were included. The 57.0% of patients were women and the mean age was 73.3±10.4 years. Patients were followed for a mean of 2.3±1.6 years. 8.7% received warfarin before the index date. The most frequent OA was rivaroxaban (n=950; 45.8%), followed by warfarin (n=459; 22.1%) and apixaban (n=405; 19.5%). Hypertension was present in 87.5% and diabetes mellitus in 22.6%. The mean CHA2DS2-VASc Score was 3.6±1.5. The 71.0% (n=326/459) of the warfarin patients presented the general composite outcome, and 24.6% of those with DOACs (n=397/1617). The main effectiveness and safety outcomes were stroke (3.1%) and gastrointestinal bleeding (2.0%) respectively. There were no significant differences between patients with warfarin and DOACs regarding thrombotic events (HR: 1.28; 95% CI: 0.68-2.42), but warfarin was associated with higher bleeding/safety events (HR: 4.29; 95% CI: 2.82-6.52) and persistence events (HR: 4.51; 95% CI: 3.81 -5.33). Conclusion: The patients with NVAF in this study were mainly older adults with multiple comorbidities. Compared to warfarin, DOACs were found to be equally effective, but safer and had a lower probability of discontinuation or switch.

Effectiveness and safety of dabigatran in Latin American patients with atrial fibrillation: Two years follow up results from GLORIA-AF registry.

BACKGROUND: Real-world data from different regions are needed to support the external validity of controlled trials and assess the impact of new oral anticoagulants (NOAC) in clinical practice. METHODS: "GLORIA-AF" is a large, ongoing, multicenter, global, prospective registry program in patients with newly diagnosed non-valvular atrial fibrillation (NVAF) at risk of stroke. Newly diagnosed patients with NVAF (within 4.5 months) and a CHA2DS2-VASc score ≥ 1 were consecutively enrolled. The study objective was to estimate the incidence rate of stroke and major bleeding after a two year follow up of patients on dabigatran that participated in the "GLORIA-AF" study (Phase II) in Latin America. RESULTS: Latin America included 378 eligible patients that received dabigatran in eight countries (Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, Perú, and Venezuela): 56.3% were male; mean age was 70.3 ± 10.8 years; 43.4% had paroxysmal AF; 36.0% persistent AF and 20.6% permanent AF. Mean CHA2DS2-VASc score was 3.2 ± 1.4; mean HAS-BLED score was 1.2 ± 0.8. Incidence rates for clinical events after 2-years of follow-up per 100 patient-years were as follows: stroke 0.33 (95% CI: 0.04-1.17), major bleeding 0.49 (95% CI: 0.10-1.42) and all-cause death 4.06 (95% CI: 2.63-6.00). Persistence with dabigatran at 6, 12 and 24 months was 91%, 86%, and 80%, respectively. CONCLUSION: These regional data shows the sustained safety and effectiveness of dabigatran over two years of follow-up, consistent with already available evidence. An increase in accessibility and incorporation of NOAC to anticoagulant treatment strategies could potentially have a positive impact on AF stroke prevention in Latin America.

Inclusion in the World Health Organization Model List of Essential Medicines of Non-Vitamin K Anticoagulants for Treatment of Non-Valvular Atrial Fibrillation: A Step Towards Reducing the Burden of Cardiovascular Morbidity and Mortality.

Non-vitamin K antagonist oral anticoagulants (NOACs) represent a paradigm shift in the treatment of non-valvular atrial fibrillation (AF) with major practice guidelines around the world recommending NOACs over vitamin K antagonist oral anticoagulants for initial treatment of AF for stroke prevention. Here we describe the evidence collated and the process followed for the successful inclusion of NOACs into the 21st WHO Model List of Essential Medicines (EML). Individual NOACs have been reported to be non-inferior or superior to warfarin in preventing stroke and systemic embolism in eligible AF patients with a reduction in the risk of stroke and systemic embolism and a lower risk of major bleeding in patients with non-valvular AF compared with warfarin in both RCTs and real-world data. The successful inclusion of NOACs in the WHO EML is an important step forward in the global fight against cardiovascular morbidity and mortality, especially in low- and middle-income countries, where the burden of disease is high and limited access to diagnosis and treatment translates into a higher burden of morbidity, mortality, and economic costs.

Patients with non-valvular atrial fibrillation on vitamin k antagonists or direct-acting oral anticoagulants: patients profile and long-term follow up outcomes.

Introduction: The arrival of direct-acting oral anticoagulants (DOACs) has led to a change in the management of non-valvular atrial fibrillation (NVAF) in recent years. The objectives of this study are to determine the level of therapeutic control of anticoagulation with vitamin K antagonists (VKA) and its possible involvement in major adverse cardiovascular events (MACE) and to evaluate differences between the group on VKA with respect to the group on DOACs. Patients and methods: Prospective cohort study that included consecutive patients diagnosed with NVAF in Cardiology Consultations with a clinical follow-up of 18 months. Demographic, clinical and analytical differences between groups were analyzed, including the level of therapeutic control of anticoagulation on the VKA group and its association with MACE. Results: Overall, 273 patients were included: 46.5% on VKA, 42.5% on DOACs, 11% without antithrombotic treatment. Patients on VKA spent 62.1% of their time within therapeutic range (TTR by the Rosendaal formule). There were no differences in MACE depending on anticoagulation control. The DOACs group presented lesser MACE rate than the VKA group (13.4 vs. 4.3%; 0.90; HR 0.90; 0.83-0.98 p = 0.01) with lower cardiovascular mortality (0.0 vs. 5.5%; HR, 0.94; 0.90-0.98; p = 0.01) and total mortality (0.9 vs. 12.6%; HR, 0.88; 0.82-0.94; p < 0.01) although without significant differences in hemorrhagic (0.9 vs. 4.7 %; p = 0.07), or ischemic events (2.6 vs. 0.8%, p = 0.27). Conclusions: Patients on VKA have a different clinical profile than those who receive DOACs. Patients on VKA have an inadequate control of the anticoagulation in quite the half of the cases. The VKA group presented more MACE than the DOACs group.

Introducción: La llegada de los anticoagulantes directos (ACD) ha supuesto un cambio en el tratamiento de la fibrilación auricular no valvular (FANV) en los últimos años. Los objetivos de este estudio son determinar el grado de control de la anticoagulación con antivitamina K (AVK) y su posible implicación en efectos cardiovasculares adversos mayores (ECAM) y evaluar las diferencias entre el grupo en tratamiento con AVK respecto del grupo con ACD. Pacientes y métodos: Estudio de cohorte prospectivo que incluyó a pacientes consecutivos diagnosticados con FANV valorados en el Servicio de Cardiología con un seguimiento de 18 meses. Se analizaron diferencias demográficas, clínicas y analíticas entre grupos, incluido el grado de control de la anticoagulación del grupo AVK y su posible relación con ECAM. Resultados: Se incluyó a 273 pacientes: 46.5% tratados con AVK, 42.5% con ACD y 11% sin tratamiento anticoagulante. El control de la anticoagulación con AVK fue del 62.1%, sin diferencias en ECAM en función de control. El grupo ACD presentó menos ECAM que el grupo de AVK (13.4 vs. 4.3%; HR, 0.90; 0.83-0.98; p = 0.01), con una menor mortalidad cardiovascular (0.0 vs. 5.5%; HR, 0.94; 0.90-0.98; p = 0.01) y total (0.9 vs. 12.6%; HR, 0.88; 0.82-0.94; p < 0,01), aunque sin diferencias significativas en eventos hemorrágicos (0.9 vs. 4.7%; p = 0.07) ni isquémicos (2.6 vs. 0.8%; p = 0.27). Discusión: Los pacientes con AVK poseen un perfil clínico diferente en comparación con los que reciben ACD. El control de anticoagulación del grupo de AVK fue inadecuado en casi la mitad de los casos. El grupo de AVK presentó más ECAM que el grupo de ACD.

Pacientes con fibrilación auricular no valvular tratados con antivitamina K o anticoagulantes directos: perfil de paciente y efectos a largo plazo / Patients with non-valvular atrial fibrillation on vitamin k antagonists or direct-acting oral anticoagulants: patients profile and long-term follow up outcomes

Resumen Introducción: La llegada de los anticoagulantes directos (ACD) ha supuesto un cambio en el tratamiento de la fibrilación auricular no valvular (FANV) en los últimos años. Los objetivos de este estudio son determinar el grado de control de la anticoagulación con antivitamina K (AVK) y su posible implicación en efectos cardiovasculares adversos mayores (ECAM) y evaluar las diferencias entre el grupo en tratamiento con AVK respecto del grupo con ACD. Pacientes y métodos: Estudio de cohorte prospectivo que incluyó a pacientes consecutivos diagnosticados con FANV valorados en el Servicio de Cardiología con un seguimiento de 18 meses. Se analizaron diferencias demográficas, clínicas y analíticas entre grupos, incluido el grado de control de la anticoagulación del grupo AVK y su posible relación con ECAM. Resultados: Se incluyó a 273 pacientes: 46.5% tratados con AVK, 42.5% con ACD y 11% sin tratamiento anticoagulante. El control de la anticoagulación con AVK fue del 62.1%, sin diferencias en ECAM en función de control. El grupo ACD presentó menos ECAM que el grupo de AVK (13.4 vs. 4.3%; HR, 0.90; 0.83-0.98; p = 0.01), con una menor mortalidad cardiovascular (0.0 vs. 5.5%; HR, 0.94; 0.90-0.98; p = 0.01) y total (0.9 vs. 12.6%; HR, 0.88; 0.82-0.94; p menor que 0,01), aunque sin diferencias significativas en eventos hemorrágicos (0.9 vs. 4.7%; p = 0.07) ni isquémicos (2.6 vs. 0.8%; p = 0.27). Discusión: Los pacientes con AVK poseen un perfil clínico diferente en comparación con los que reciben ACD. El control de anticoagulación del grupo de AVK fue inadecuado en casi la mitad de los casos. El grupo de AVK presentó más ECAM que el grupo de ACD.

Abstract Introduction: The arrival of direct-acting oral anticoagulants (DOACs) has led to a change in the management of non-valvular atrial fibrillation (NVAF) in recent years. The objectives of this study are to determine the level of therapeutic control of anticoagulation with vitamin K antagonists (VKA) and its possible involvement in major adverse cardiovascular events (MACE) and to evaluate differences between the group on VKA with respect to the group on DOACs. Patients and methods: Prospective cohort study that included consecutive patients diagnosed with NVAF in Cardiology Consultations with a clinical follow-up of 18 months. Demographic, clinical and analytical differences between groups were analyzed, including the level of therapeutic control of anticoagulation on the VKA group and its association with MACE. Results: Overall, 273 patients were included: 46.5% on VKA, 42.5% on DOACs, 11% without antithrombotic treatment. Patients on VKA spent 62.1% of their time within therapeutic range (TTR by the Rosendaal formule). There were no differences in MACE depending on anticoagulation control. The DOACs group presented lesser MACE rate than the VKA group (13.4 vs. 4.3%; 0.90; HR 0.90; 0.83-0.98 p = 0.01) with lower cardiovascular mortality (0.0 vs. 5.5%; HR, 0.94; 0.90-0.98; p = 0.01) and total mortality (0.9 vs. 12.6%; HR, 0.88; 0.82-0.94; p less 0.01) although without significant differences in hemorrhagic (0.9 vs. 4.7 %; p = 0.07), or ischemic events (2.6 vs. 0.8%, p = 0.27). Conclusions: Patients on VKA have a different clinical profile than those who receive DOACs. Patients on VKA have an inadequate control of the anticoagulation in quite the half of the cases. The VKA group presented more MACE than the DOACs group.

XANTUS-EL: A real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation in Eastern Europe, Middle East, Africa and Latin America.

BACKGROUND: The prospective, observational XANTUS study demonstrated low rates of stroke and major bleeding in real-world rivaroxaban-treated patients with non-valvular atrial fibrillation (NVAF) from Western Europe, Canada and Israel. XANTUS-EL is a component of the overall XANTUS programme and enrolled patients with NVAF treated with rivaroxaban from Eastern Europe, the Middle East and Africa (EEMEA) and Latin America. METHODS: Patients with NVAF starting rivaroxaban for stroke prevention were consecutively recruited and followed for 1 year, at approximately 3-month intervals, or for ≥30 days after permanent rivaroxaban discontinuation. Primary outcomes were major bleeding, adverse events (AEs), serious AEs and all-cause mortality. Secondary outcomes included stroke, non-central nervous system systemic embolism (non-CNS SE), transient ischaemic attack (TIA), myocardial infarction (MI) and non-major bleeding. All major outcomes were centrally adjudicated. RESULTS: Overall, 2064 patients were enrolled; mean age ±â€¯standard deviation was 67.1 ±â€¯11.32 years; 49.3% were male. Co-morbidities included heart failure (30.9%), hypertension (84.2%), diabetes mellitus (26.5%), prior stroke/non-CNS SE/TIA (16.2%) and prior MI (10.7%). Mean CHADS2, CHA2DS2-VASc and HAS-BLED scores were 2.0, 3.6 and 1.6, respectively. Treatment-emergent event rates were (events/100 patient-years, [95% confidence interval]): major bleeding 0.9 (0.5-1.4); all-cause mortality 1.7 (1.2-2.4); stroke/non-CNS SE 0.7 (0.4-1.2); any AE 18.1 (16.2-20.1) and any serious AE 8.3 (7.0-9.7). One-year treatment persistence was 81.9%. CONCLUSIONS: XANTUS-EL confirmed low stroke and major bleeding rates in patients with NVAF from EEMEA and Latin America. The population was younger but with more heart failure and hypertension than XANTUS; stroke/SE rate was similar but major bleeding lower.

Manejo perioperatorio del paciente anticoagulado con fibrilación auricular no valvular / Perioperative management of the anticoagulated patient with non-valvular atrial fibrillation

Resumen: La fibrilación auricular (FA) aumenta el riesgo de accidente cerebrovascular (ACV) y tromboembolia (TE) sistémica, por lo que resulta fundamental prevenir esta temible complicación a través del tratamiento anticoagulante. Al uso habitual de warfarina se agregaron en los últimos años los anticoagulantes orales directos (ACOD). Frente a una intervención, o procedimiento invasivo es necesario evaluar el riesgo embólico y el de sangrado para definir el manejo más adecuado de estos fármacos. En el presente artículo se proponen recomendaciones para el tratamiento anticoagulante periprocedimiento en la fibrilación auricular no valvular basadas en el consenso de expertos del American College of Cardiology.

Summary: Atrial fibrillation increases the risk of stroke and systemic embolism, so it is important to prevent this terrible complication with anticoagulant therapy. To the usual use of warfarin were added in recent years, direct anticoagulants. In front of an invasive procedure, it is necessary to evaluate embolism and bleeding risks to define the most appropriate management of these drugs. In the present article, recommendations based in expert consensus of American College of Cardiology are proposed, to periprocedural anticoagulation treatment in non-valvular atrial fibrillation.

Non-Pharmacologic Approach to Prevent Embolization in Patients with Atrial Fibrillation in Whom Anticoagulation is Contraindicated.

Ischemic stroke is the most common complication of atrial fibrillation (AF). Anticoagulation therapy reduces the risk of systemic embolization in almost all patients with AF irrespective of the type of AF (paroxysmal, persistent or permanent). But, all patients are not suitable candidates for systemic anticoagulation mainly due to the risk of bleeding. Left atrial appendage closure (LAAC) devices have been found to be very effective non-pharmacologic alternative therapy for such patients. There are various types of LAAC devices but United States Food and Drug Administration (US-FDA) have approved only Watchman device. Initially, bigger medical centers in the US had started the insertion of Watchman device but with improving procedural techniques and exciting outcomes, even the community-based hospitals have started to embrace this therapy. We have presented the first three cases of Watchman device placement performed in our hospital and discussed about the indications for placement of LAAC devices. We have also reviewed their efficacy individually.

Outcome, Recurrence and Mortality after Non-Valvular Atrial Fibrillation Stroke: Long-Term Follow-Up Study.

OBJECTIVE: Non-valvular atrial fibrillation (NVAF) is a major risk factor for ischemic stroke (IS) and a powerful predictor of mortality. This study investigates early and long-term outcome among patients with IS secondary to NVAF and identify the main factors associated with poor outcome, recurrence, and death. METHODS: We analyzed the data from our consecutive NVAF acute IS database, over a period of 23 years. The endpoints were bad outcome (Modified Rankin Score ≥3), recurrence, and mortality at discharge, after 6 months, 12 months, and final follow-up. Multivariate Cox and Kaplan-Meier analysis were used to estimate the probability of death. RESULTS: 129 consecutive acute IS patients were included (77 [59.7%] females, mean age 70.2 ± 10.1 years). Discharge, 6 and 12 months bad outcome was 62%, 63%, and 61%, respectively. After a median follow-up of 17 months (IQR 6-54.5), 35.6% patients had bad outcome, 21.7% had recurrence and 36.4% died. The recurrence and death annual rates were 19.1% and 6.32%. The absence of oral anticoagulation (OAC) and NIHSS score > 12 were the strongest predictors of mortality. CONCLUSIONS: IS secondary to NVAF has a high rate of stroke recurrence and mortality in our population, with the absence of OAC and major stroke as the main risk factors.

Rivaroxaban for treatment of intraventricular thrombus in Chagas disease.

Chagas disease leads to congestive heart failure, apical aneurysm, and may cause stroke or systemic embolism for intraventricular thrombus. We present a case of a 61-year-old man admitted for stroke 5 months after a renal embolism. An intraventricular thrombus was observed, probably the source of the cerebral and renal embolisms. The patient refused warfarin and rivaroxaban was used instead. After 40 days of treatment the thrombus had dissolved, after 20 months of regular use of rivaroxaban no more embolic events were observed. The use of rivaroxaban was effective in preventing embolic events in Chagas disease and intraventricular thrombus. .

Una enfermedad prevenible: el accidente cerebrovascular en la fibrilación auricular no valvular. ¿Qué lugar ocupan los nuevos anticoagulantes orales? / A preventable disease: stroke in non-valvular atrial fibrillation. What is the role of the new oral anticoagulants?

La fibrilación auricular no valvular (FANV) es la arritmia cardíaca sostenida más frecuente. El accidente cerebrovascular (ACV) asociado a la (FANV), es una complicación devastadora, prevenible, con secuelas neurológicas, recurrencias, mortalidad precoz y al año mayor que el (ACV) no asociado a la (FANV). La warfarina demostró en prevención primaria una reducción del riesgo de 64%. El presente trabajo aborda nuevos scores de riesgo de embolia en la (FANV), riesgo de sangrado, y los resultados de 3 trabajos multicéntricos que comparan dabigatran, rivaroxaban y apixaban vs. warfarina en prevención del (ACV) asociado a (FANV). Intenta, de acuerdo a lo anterior, un posicionamiento de los nuevos anticoagulantes orales (NAO) como opción frente a la warfarina. Realiza consideraciones prácticas generales y en situaciones puntuales para el uso de los (NAO).

Una enfermedad prevenible: el accidente cerebrovascular en la fibrilación auricular no valvular. ¿Qué lugar ocupan los nuevos anticoagulantes orales? / A preventable disease: stroke in non-valvular atrial fibrillation. What is the role of the new oral anticoagulants?

La fibrilación auricular no valvular (FANV) es la arritmia cardíaca sostenida más frecuente. El accidente cerebrovascular (ACV) asociado a la (FANV), es una complicación devastadora, prevenible, con secuelas neurológicas, recurrencias, mortalidad precoz y al año mayor que el (ACV) no asociado a la (FANV). La warfarina demostró en prevención primaria una reducción del riesgo de 64%. El presente trabajo aborda nuevos scores de riesgo de embolia en la (FANV), riesgo de sangrado, y los resultados de 3 trabajos multicéntricos que comparan dabigatran, rivaroxaban y apixaban vs. warfarina en prevención del (ACV) asociado a (FANV). Intenta, de acuerdo a lo anterior, un posicionamiento de los nuevos anticoagulantes orales (NAO) como opción frente a la warfarina. Realiza consideraciones prácticas generales y en situaciones puntuales para el uso de los (NAO).

Una enfermedad prevenible: el accidente cerebrovascular en la fibrilación auricular no valvular. ¿Qué lugar ocupan los nuevos anticoagulantes orales? / A preventable disease: stroke in non-valvular atrial fibrillation. What is the role of the new oral anticoagulants?

La fibrilación auricular no valvular (FANV) es la arritmia cardíaca sostenida más frecuente. El accidente cerebrovascular (ACV) asociado a la (FANV), es una complicación devastadora, prevenible, con secuelas neurológicas, recurrencias, mortalidad precoz y al año mayor que el (ACV) no asociado a la (FANV). La warfarina demostró en prevención primaria una reducción del riesgo de 64%. El presente trabajo aborda nuevos scores de riesgo de embolia en la (FANV), riesgo de sangrado, y los resultados de 3 trabajos multicéntricos que comparan dabigatran, rivaroxaban y apixaban vs. warfarina en prevención del (ACV) asociado a (FANV). Intenta, de acuerdo a lo anterior, un posicionamiento de los nuevos anticoagulantes orales (NAO) como opción frente a la warfarina. Realiza consideraciones prácticas generales y en situaciones puntuales para el uso de los (NAO).

Non valvular atrial fibrillation (NVAF) is the most common sustained arrhythmia. NVAF-associated stroke is a devastating, preventable condition with neurological sequels, recurrences, early mortality and greater than NVAF-independent stroke annually. Warfarin showed a 64% risk reduction in primary prevention. The paper herein approaches new risk scores for embolism in NVAF, risk for bleeding, and the results of 3 multicentric studies comparing dabigatran, rivaroxaban and apixaban vs. Warfarin in the prevention of NVAF-associated stroke. Based on the above, it is intended to position the new oral anticoagulants (NOA) as a potential option vis à vis warfarin. The authors reach practical considerations, both general and in specific situations for the use of NOAs.