Aortic valve stenosis provides complementary information to bleeding risk scores in non-valvular atrial fibrillation patients initiating anticoagulation.

BACKGROUND: The identification of modifiable bleeding risk factors may be of relevance. The aim is to evaluate if aortic stenosis (AS) provides additional information to bleeding risk scores for predicting major bleeding (MB) in non-valvular atrial fibrillation (AF). METHODS: We designed a retrospective multi-center study including 2880 consecutive non-valvular AF patients initiating oral anticoagulation between January 2013 and December 2016. AS was defined as moderate or severe according to European echocardiography guidelines criteria. HASBLED, ATRIA and ORBIT scores were used to evaluate the bleeding risk. MB was defined according to the International Society on Thrombosis and Haemostasia criteria and registered at 18 months of follow-up. RESULTS: 168 (5.8%) patients had AS. Patients with AS had higher risk for MB compared to those without AS (HR = 2.13, 95% CI: 1.40-3.23, P < 0.001). Patients without AS and low-intermediate bleeding risk (0 points) showed the lowest MB rate, whereas the MB rate observed among patients with AS and high bleeding risk (2 points) was the highest one. Discrimination and reclassification analyses showed that AS provided additional information to bleeding risk scores for predicting MB at 18 months of follow-up. CONCLUSIONS: In this population, AS was associated with an increased risk for MB at midterm follow-up. The three scoring systems showed a moderate discriminatory ability for MB. Moreover, the addition of AS was associated with a significant improvement in their predictive accuracy. We suggest that the presence of this valvulopathy should be taken into account for bleeding risk assessment.

Prevalencia e implicación pronóstica de la enfermedad valvular en pacientes con fibrilación auricular que inician anticoagulantes orales / Prevalence and prognostic implications of valve disease in patients with atrial fibrillation initiating direct oral anticoagulants

Introducción y objetivos: La enfermedad valvular en los pacientes con fibrilación auricular incluidos en los ensayos clínicos con anticoagulantes orales directos (ACOD) es frecuente y se asocia con peor pronóstico. El objetivo es evaluar la prevalencia de valvulopatía y su influencia en los eventos clínicos en la práctica clínica real. Métodos: Registro multicéntrico retrospectivo que incluyó a 2.297 pacientes consecutivos con fibrilación auricular no valvular que iniciaron tratamiento con ACOD entre enero de 2013 y diciembre de 2016. La enfermedad valvular se definió como afección moderada o grave. El evento principal fue la combinación de muerte, ictus o accidente isquémico transitorio/embolia sistémica o hemorragia mayor. Se realizó un análisis de riesgos competitivos mediante un modelo de regresión de Fine y Gray, con la muerte como evento competitivo. Resultados: Tenían valvulopatía 499 pacientes (21,7%), y la insuficiencia mitral fue la más frecuente (13,7%). Los pacientes con valvulopatía eran de más edad y con mayor comorbilidad. Tras el análisis multivariable, la enfermedad valvular fue predictora del evento combinado (HR=1,54; IC95%, 1,22-1,94; p<0,001), muerte (HR=1,44; IC95%, 1,09-1,91, p=0,010) y hemorragia mayor (HR=1,85; IC95%, 1,23-2,79, p=0,003), pero no de eventos tromboembólicos (p >0,05). Conclusiones: En pacientes con fibrilación auricular no valvular que inician tratamiento con ACOD, la enfermedad valvular es frecuente y se asocia con mayor riesgo de muerte, ictus o accidente isquémico transitorio/embolia sistémica o complicaciones hemorrágicas. Estos hallazgos confirman los resultados de los ensayos clínicos y los expande al ámbito de la práctica clínica real

Introduction and objectives: Valvular heart disease in patients with atrial fibrillation included in clinical trials with direct oral anticoagulants (DOAC) is common and is associated with worse prognosis. The aim of this study was to evaluate the prevalence of valvular heart disease and its influence on clinical events in real-world clinical practice. Methods: We conducted a retrospective multicenter registry including 2297 consecutive patients with nonvalvular atrial fibrillation initiating DOAC between January 2013 and December 2016. Valvular heart disease was defined as moderate or severe involvement. The primary study endopoint was the composite of death, stroke or transient ischemic attack/systemic embolism or major bleeding. A competing risks analysis was carried out using a Fine and Gray regression model, with death being the competing event. Results: A total of 499 (21.7%) patients had significant valvular heart disease. The most common form was mitral regurgitation (13.7%). Patients with valvular heart disease were older and had more comorbidities. After multivariable analysis, valvular heart disease was associated with a higher risk for the primary endpoint (HR, 1.54; 95%CI, 1.22-1.94; P<.001), death (HR, 1.44; 95%CI, 1.09-1.91, P=.010), and major bleeding (HR, 1.85; 95%CI, 1.23-2.79, P=.003), but there was no association with thromboembolic events (P >.05). Conclusions: In patients with nonvalvular atrial fibrillation initiating DOACs, valvular heart disease is common and increases the risk of mortality, stroke, transient ischemic attack/systemic embolism, and major bleeding complications. These findings confirm the results of clinical trials and expand them to a real-life clinical setting

Effect of concomitant antiplatelet therapy in patients with nonvalvular atrial fibrillation initiating non-vitamin K antagonists.

BACKGROUND: Antiplatelet therapy (APT) use in combination with oral anticoagulation is common among patients with atrial fibrillation, but there is scarce information regarding its effect on outcomes in patients on non-vitamin K antagonist oral anticoagulants (NOAC). We aimed to evaluate the safety and efficacy of APT use in a 'real-world' cohort of nonvalvular atrial fibrillation (NVAF) patients initiating NOAC. DESIGN: We conducted a retrospective multicentre study including 2361 consecutive NVAF patients initiating NOAC between January 2013 and December 2016. Patients with an acute ischaemic event within the last 12 months (acute coronary syndrome, stroke or revascularization) were excluded. Patients were followed up, and all clinical events were recorded at 3 months. The primary outcome of the study was major bleeding, and the secondary outcomes were stroke, nonfatal myocardial infarction, intracranial bleeding and death. RESULTS: One hundred forty-five (6.1%) patients received concomitant APT, and aspirin was the more common (79%). At 3 months, 25 (1.1%) patients had major bleeding, 8 (0.3%) had nonfatal myocardial infarction, 7 (0.3%) had ischaemic stroke, and 40 (1.7%) died. After multivariate adjustment, concomitant APT was associated with higher risk for major bleeding (HR = 3.62, 95% CI 1.32-9.89; P = .012), but was not associated with a higher risk of other clinical outcomes. CONCLUSIONS: Concomitant APT use is uncommon among these patients and does not seem to be associated with lower rates of ischaemic events or death. However, there are signals for an increased risk of bleeding, which reinforces current guideline recommendations.

Real-life behaviour of direct oral anticoagulants in a Spanish cohort with non-valvular atrial fibrillation: Refase Registry.

Aim: To analyse the effectiveness and safety of DOAC (direct oral anticoagulants) in non-valvular atrial fibrillation (NVAF) patients attending clinical practice.Methods: Retrospective study of AF patients who started treatment with DOAC from January 1, 2013 to December 31, 2016 in three Spanish hospitals. Mean follow-up was 1.6 years. The primary outcomes were rates of all-cause death, ischaemic stroke, and bleeding. These outcomes were also studied depending on correct dosage adjustment and standard/adjusted dose.Results: The study included 2494 patients (age = 76.0 ± 9.5 years, CHA2DS2-VASc = 4.0 ± 1.6). The most prescribed DOAC was rivaroxaban (41.1%). Patients taking dabigatran were the youngest (mean age = 73.1 ± 10.3 years), with better kidney function (mean CrCl = 80.6 ± 35.8 ml/min) and lower CHA2DS2-VASc (3.7 ± 1.4) and HAS-BLED (2.1 ± 0.9) scores. Patients taking apixaban were the oldest, and had the highest CHA2DS2-VASc and HAS-BLED scores (4.3 ± 1.6 and 2.6 ± 0.9, respectively). Rates of stroke/major bleeding/intracranial bleeding were 1.8/3.0/0.3 events per 100 patient-years, respectively, with no differences among DOAC. Based on dose adjustment according to technical data, it was observed that 517 patients (23.5%) received DOAC doses inconsistent with labelling (p < .001) and, within this group, under-dosed patients had a higher death rate although it did not reach a significant result after multivariate adjustment.Conclusions: The results of safety and efficacy are very similar to those of other previously published national registries. There were no differences among the different types of DOAC regarding outcomes. However, it was found that people taking the adjusted dose of the drug seemed to have a higher risk of death. A non-negligible proportion of patients received DOAC doses inconsistent with labelling (mostly underdose).

Effectiveness and safety of rivaroxaban in nonvalvular atrial fibrillation: data from a contemporary Spanish registry.

Objective: To ascertain the clinical profile, management and rates of thromboembolic and bleeding complications in a contemporary cohort of patients with nonvalvular atrial fibrillation (NVAF) on rivaroxaban treatment, with a particular focus on some subgroups of patients. Methods: Retrospective study that included all NVAF patients who started treatment with rivaroxaban for the prevention of stroke or systemic embolism between December 2012 and December 2015. Rates of outcomes (stroke, nonfatal myocardial infarction, major bleeding, intracranial bleeding and death) during follow-up were calculated. Results: A total of 732 patients (mean age 76.4 ± 9.2 years; 54.5% women) were included. Comorbidities were common (hypertension 87.5%; diabetes 26.5%; renal insufficiency 24.6%; prior stroke/transient ischemic attack 16.8%). Mean CHA2DS2-VASc was 3.9 ± 1.5 and HAS-BLED 2.3 ± 0.9; 61.9% of patients were rivaroxaban naïve users. After a mean treatment period of 22.7 ± 7.4 months, rates of stroke, nonfatal myocardial infarction, major bleeding, intracranial bleeding and death were 1.8, 1.0, 3.2, 0.4 and 5.5 events per 100 patient-years, respectively. Rates of stroke and death were higher in patients >75 years (vs. ≤75 years) and in patients with prior stroke/transient ischemic attack or renal insufficiency. Rates of major bleeding were higher among patients >75 years and in patients with prior stroke/transient ischemic attack. Conclusions: In this contemporary Spanish cohort of NVAF patients on rivaroxaban, patients had many comorbidities, a high thromboembolic risk and a moderate bleeding risk. Overall, rates of stroke and bleeding complications were low and similar to other previous studies. These data suggest that rivaroxaban is effective and safe in routine practice.

Prevalence and Prognostic Implications of Valve Disease in Patients With Atrial Fibrillation Initiating Direct Oral Anticoagulants.

INTRODUCTION AND OBJECTIVES: Valvular heart disease in patients with atrial fibrillation included in clinical trials with direct oral anticoagulants (DOAC) is common and is associated with worse prognosis. The aim of this study was to evaluate the prevalence of valvular heart disease and its influence on clinical events in real-world clinical practice. METHODS: We conducted a retrospective multicenter registry including 2297 consecutive patients with nonvalvular atrial fibrillation initiating DOAC between January 2013 and December 2016. Valvular heart disease was defined as moderate or severe involvement. The primary study endopoint was the composite of death, stroke or transient ischemic attack/systemic embolism or major bleeding. A competing risks analysis was carried out using a Fine and Gray regression model, with death being the competing event. RESULTS: A total of 499 (21.7%) patients had significant valvular heart disease. The most common form was mitral regurgitation (13.7%). Patients with valvular heart disease were older and had more comorbidities. After multivariable analysis, valvular heart disease was associated with a higher risk for the primary endpoint (HR, 1.54; 95%CI, 1.22-1.94; P<.001), death (HR, 1.44; 95%CI, 1.09-1.91, P=.010), and major bleeding (HR, 1.85; 95%CI, 1.23-2.79, P=.003), but there was no association with thromboembolic events (P >.05). CONCLUSIONS: In patients with nonvalvular atrial fibrillation initiating DOACs, valvular heart disease is common and increases the risk of mortality, stroke, transient ischemic attack/systemic embolism, and major bleeding complications. These findings confirm the results of clinical trials and expand them to a real-life clinical setting.