Impact of New Onset Atrial Fibrillation in Hospitalized Patients with COVID-19. Results of the "ACO-VID" Registry.

OBJECTIVE: To assess the impact of new-onset atrial fibrillation (AF) on patients hospitalized with coronavirus disease 2019 (COVID-19). METHODS: Multicenter and retrospective study that included subjects >55 years hospitalized with COVID-19 from March to October 2020 in Spanish hospitals. Patients were divided into 3 groups (no AF, new-onset AF, and preexisting AF) and followed-up to 90 days. RESULTS: A total of 668 patients were included, of whom 162 (24.3%) had no AF, 107 (16.0%) new-onset AF and 399 (59.7%) preexisting AF. Compared to patients without AF, those patients with new-onset AF were older and had more comorbidities, but without differences with preexisting AF. During hospitalization, in the univariate analysis, compared to patients without AF, major bleeding and cardiovascular mortality were more frequent in patients with new-onset AF (10.3% vs 0.6%; P < .001; 2.8% vs 0.6%; P = .025, respectively), with a trend toward more stroke (1.9% vs 0%; P = .085). Outcomes were similar between AF groups, but the length of stay was greater in preexisting AF patients. Among patients with new-onset AF taking reduced doses of anticoagulant treatment was associated with higher risks of stroke and major bleeding. CONCLUSIONS: In COVID-19 hospitalized patients, new-onset AF may be associated with worse outcomes, but influenced by the dose of anticoagulants.

Edoxaban Versus Low-Molecular-Weight Heparin in Hospitalized COVID-19 Patients With Atrial Fibrillation.

OBJECTIVE: During the first wave of the SARS-CoV-2 pandemic, management of anticoagulation therapy in hospitalized patients with atrial fibrillation (AF) was simplified to low-molecular-weight heparin (LMWH) followed by oral anticoagulation, mainly owing to the risk of drug-drug interactions. However, not all oral anticoagulants carry the same risk. METHODS: Observational, retrospective, and multicenter study that consecutively included hospitalized patients with AF anticoagulated with LMWH followed by oral anticoagulation or edoxaban concomitantly with empirical COVID-19 therapy. Time-to-event (mortality, total bleeds, and admissions to ICU) curves, using an unadjusted Kaplan-Meier method and Cox regression model adjusted for potential confounders were constructed. RESULTS: A total of 232 patients were included (80.3 ± 7.7 years, 50.0% men, CHA2DS2-VASc 4.1 ± 1.4; HAS-BLED 2.6 ± 1.0). During hospitalization, patients were taking azithromycin (98.7%), hydroxychloroquine (89.7%), and ritonavir/lopinavir (81.5%). The mean length of hospital stay was 14.6 ± 7.2 days, and total follow-up was 31.6 ± 13.4 days; 12.9% of patients required admission to ICU, 18.5% died, and 9.9% had a bleeding complication (34.8% major bleeding). Length of hospital stay was longer in patients taking LMWH (16.0 ± 7.7 vs 13.3 ± 6.5 days; P = .005), but mortality and total bleeds were similar in patients treated with edoxaban and those treated with LMWH followed by oral anticoagulation. CONCLUSIONS: Mortality rates, arterial and venous thromboembolic complications, and bleeds did not significantly differ between AF patients receiving anticoagulation therapy with edoxaban or LMWH followed by oral anticoagulation. However, the duration of hospitalization was significantly lower with edoxaban. Edoxaban had a similar therapeutic profile to LMWH followed by oral anticoagulation and may provide additional benefits.

Impact of atrial fibrillation and anticoagulation on the risk of death, thromboembolic disease and bleeding in patients with COVID-19: the ACO-VID Registry.

OBJECTIVE: To describe the clinical profile, risk of complications and impact of anticoagulation in COVID-19 hospitalized patients, according to the presence of atrial fibrillation (AF). METHODS: Multicenter, retrospective, and observational study that consecutively included patients >55 years admitted with COVID-19 from March to October 2020. In AF patients, anticoagulation was chosen based on clinicians' judgment. Patients were followed-up for 90 days. RESULTS: A total of 646 patients were included, of whom 75.2% had AF. Overall, mean age was 75 ± 9.1 years and 62.4% were male. Patients with AF were older and had more comorbidities. The most common anticoagulants used during hospitalization in patients with AF were edoxaban (47.9%), low molecular weight heparin (27.0%), and dabigatran (11.7%) and among patients without AF, these numbers were 0%, 93.8% and 0%. Overall, during the study period (68 ± 3 days), 15.2% of patients died, 8.2% of patients presented a major bleeding and 0.9% had a stroke/systemic embolism. During hospitalization, patients with AF had a higher risk of major bleeding (11.3% vs 0.7%; p < .01), COVID-19-related deaths (18.0% vs 4.5%; p = .02), and all-cause deaths (20.6% vs 5.6%; p = .02). Age (HR 1.5; 95% CI 1.0-2.3) and elevated transaminases (HR 3.5; 95% CI 2.0-6.1) were independently associated with all-cause mortality. AF was independently associated with major bleeding (HR 2.2; 95% CI 1.1-5.3). CONCLUSIONS: Among patients hospitalized with COVID-19, patients with AF were older, had more comorbidities and had a higher risk of major bleeding. Age and elevated transaminases during hospitalization, but not AF nor anticoagulant treatment increased the risk of all-cause death.

Dabigatran in patients with atrial fibrillation after COVID-19 hospitalization: an update of the ANIBAL protocol.

COVID-19 increases the risk of atrial fibrillation (AF) and thrombotic complications, particularly in severe cases, leading to higher mortality rates. Anticoagulation is the cornerstone to reduce thromboembolic risk in patients with AF. Considering the risk of hepatotoxicity in patients with severe COVID-19 as well as the risk of drug-drug interactions, drug-induced hepatotoxicity and bleeding, the ANIBAL protocol was developed to facilitate the anticoagulation approach at discharge after COVID-19 hospitalization. However, since the publication of the original algorithm, relevant changes have occurred. First, treatment of COVID-19 pneumonia has been modified with the use of dexamethasone or remdesivir during the first week in patients that require oxygen therapy, and of dexamethasone and/or tocilizumab or baricitinib during the second week in patients that necessitate supplementary oxygen or with a high inflammation state, respectively. On the other hand, metabolic syndrome is common in patients with AF as well as metabolic-associated fatty liver disease, and this could negatively impact the prognosis of patients with COVID-19, including high transaminase levels in patients treated with immunomodulators. The EHRA guidelines update also introduce some interesting changes in drug-drug interaction patterns with the reduction of the level of the interaction with dexamethasone, which is of paramount importance in this clinical context. Considering the new information, the protocol, named ANIBAL II, has been updated. In this new protocol, the anticoagulant of choice in patients with AF after COVID-19 hospitalization is provided according to three scenarios: with/without dexamethasone treatment at discharge and normal hepatic function, transaminases ≤2 times the upper limit of normal, or transaminases >2 times the upper limit of normal.

Real life behaviour of direct oral anticoagulants in patients with nonvalvular atrial fibrillation and morbid obesity.

Atrial fibrillation (AF) is the most prevalent arrhythmia worldwide and the main cause of anticoagulation, being direct oral anticoagulants (DOAC) increasingly used in this context. On the other hand, obesity is a known risk thromboembolic factor. In the clinical trials that led to the approval of DOAC for ischemic stroke prevention, patients with morbid obesity were underrepresented. The International Society of Thrombosis and Haemostasis suggests not using these drugs in morbid obese patients. Thus, the primary objectives of this study were to analyse the rates of mortality, thrombotic and haemorrhagic events in patients with morbid obesity. As secondary objectives, factors statistically associated with these events were analysed. Methods: multicentre retrospective study that included patients diagnosed with AF on treatment with DOAC from January 2013 to December 2016. The subgroup of patients with morbid obesity (BMI > 40 and / or weight > 120 kg) was analysed. Mean follow-up was 1.7 years. Results: Amongst 2,492 patients included in the study, 135 patients had morbid obesity (mean age was 71 ± 11 years). The mean scores of the CHA2DS2-VASc and HAS-BLED risk scales were 3.7 ± 1.6 and 2.2 ± 0.9, respectively. Neither differences were found regarding mortality (5.2 vs 6/100 patient-years, p = 0.662), ischemic stroke (0.8 vs 1.9/100 patient-years, p = 0.261) and major bleeding rates (3 vs 3.1/100 patient-years, p = 0.983) between morbidly obese population and general population. Nor was there an association found between the degree of obesity and any of the events studied. Conclusion: DOAC are safe and effective in morbidly obese patients.

Treatment preferences as basis for decision making in patients using direct oral anticoagulants in Spain.

Treatment preferences are considered a relevant decision-making driver by the main atrial fibrillation (AF) guidelines. Direct Oral Anticoagulants (DOACs), considered as similar clinically, have administration differences useful for treatment individualization. Preferences, priorities and satisfaction of DOAC users were assessed through an observational, multicentric (25 hospitals), cross-sectional study including adult AF-patients (and/or caregivers) in Spain. Three study groups were considered according to DOAC posology preferences: (A) once-daily, with water; (B) once-daily, with food; (C) twice-daily. Overall, 332 patients and 55 caregivers were included. Mean (SD) age was 73.7 (10.7) years [58.7 (13.9) for caregivers]; 51.5% women [69.1% for caregivers]; 80.7% showed comorbidities and poly-pharmacy [6.6 (3.3) drugs/day]. No statistically significant differences were shown among study groups. Once-daily administration was preferred by 274 patients (82.5%) [60.8% (Group A); 21.7% (Group B); 17.5% (Group C)], and 47 caregivers (85.5%) [58.2% (Group A); 27.3% (Group B); 14.5% (Group C)]. Once-daily DOACs were prescribed in 42.8% of the patients. Bleeding risk was the main concern for both, patients and caregivers, followed by DOAC posology and interactions. Although treatment satisfaction (patients and caregivers) was high (9.0 and 9.1 points, respectively), match between individual treatment preferences and real prescriptions was only shown in 41.0% of AF-patients, evidencing a need for patient involvement on treatment decision-making. There is not a patient profile linked to treatment preferences, and clinical criteria must be the main driver for decision-making. However, for most AF-patients (elderly patients), aged, with comorbidity, poly-pharmacy and high cardiovascular risk, once-daily DOACs would be the preferred option.

Dabigatran, the oral anticoagulant of choice at discharge in patients with non-valvular atrial fibrillation and COVID-19 infection: the ANIBAL protocol.

Atrial fibrillation is a frequent complication among patients with severe coronavirus disease-2019 (COVID-19) infection. Both direct and indirect mechanisms through COVID-19 have been described to explain this relationship. COVID-19 infection increases the risk of developing both arterial and venous thrombotic complications through systemic coagulation activation, leading to increased mortality. Chronic oral anticoagulation is essential to reduce the thromboembolic risk among AF patients. Switching to low-molecular-weight heparin has been recommended during hospitalization for COVID-19 infection. Of note, at discharge, the prescription of direct oral anticoagulants may offer some advantages over vitamin K antagonists. However, oral anticoagulants should only be prescribed after the consideration of drug-drug interactions with antiviral therapies as well as of the risk of hepatotoxicity, which is common among individuals with severe COVID-19 pneumonia. Not all anticoagulants have the same risk of hepatotoxicity; dabigatran has shown a good efficacy and safety profile and could have a lower risk of hepatotoxicity. Furthermore, its metabolism by cytochrome P450 is absent and it has a specific reversal agent. Therefore, dabigatran may be considered as a first-line choice for oral anticoagulation at discharge after COVID-19 infection. In this review, the available information on the antithrombotic management of AF patients at discharge after COVID-19 infection is updated. In addition, a practical algorithm, considering renal and liver function, which facilitates the anticoagulation choice at discharge is presented.

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.

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.

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.

Effectiveness and safety of rivaroxaban in a cohort of 142 patients with nonvalvular atrial fibrillation treated with rivaroxaban for the prevention of stroke.

AIM: To evaluate the clinical profile and effectiveness/safety of patients taking rivaroxaban in clinical practice. METHODS: Retrospective study that included patients with nonvalvular atrial fibrillation treated with rivaroxaban for the prevention of stroke between January 2012 and December 2016 in a tertiary hospital in Spain. RESULTS: A total of 142 patients (median age 78 years, 40.1% men, 32.4% creatinine clearance <50 ml/min; 96.5% CHA2DS2-VASc ≥2; 44.3% HAS-BLED ≥3) were included. Only two patients had a thromboembolic event (in both cases ischemic stroke) and three patients had major bleeding (rates of 1.3 and 1.9 events/100 patient years, respectively). CONCLUSION: Data regarding effectiveness and safety in our cohort were consistent with previous studies, showing that rivaroxaban can be effective and safely used in our setting.

Kidney function monitoring and nonvitamin K oral anticoagulant dosage in atrial fibrillation.

BACKGROUND: Clinical practice guidelines recommend regular kidney function monitoring in atrial fibrillation patients on nonvitamin K oral anticoagulants (NOAC); however, information regarding compliance with these recommendations in daily life conditions is scarce. We sought to determine the compliance with kidney function monitoring recommendations in nonvalvular atrial fibrillation (NVAF) patients starting NOAC and its implication on the appropriateness of NOAC dosage. MATERIAL AND METHODS: This study involves the retrospective analysis of a multicentre registry including consecutive NVAF patients who started NOAC (n = 692). Drug dosage changes and serum creatinine determinations were recorded during 1-year follow-up. European Heart Rhythm Association criteria were used to define the appropriateness of kidney function monitoring as well as adequate NOAC dosage. RESULTS: During the follow-up (334 ± 89 days), the compliance with kidney function monitoring recommendations was 61% (n = 425). After multivariate adjustment, age (OR × year: 0.92 (CI 95%: 0.89-0.95) P < .001), creatinine clearance (OR × mL/min: 1.02 (CI 95%: 1.01-1.03) P < .001) and adequate NOAC dosage at baseline (OR: 1.54 (CI 95%: 1.06-2.23), P = .024) were independent predictors of appropriate kidney function monitoring. Compliance with kidney function monitoring recommendations was independently associated with change to appropriate NOAC dose after 1 year (OR: 2.80 (CI 95%: 1.01-7.80), P = .049). CONCLUSIONS: Noncompliance with kidney function monitoring recommendations is common in NVAF patients starting NOAC, especially in elderly patients with kidney dysfunction. Compliance with kidney function monitoring recommendations was associated with adequate NOAC dosage at 1-year follow-up. Further studies are warranted to evaluate the implication of kidney function monitoring on prognosis.

Genotype-guided therapy improves initial acenocoumarol dosing. Results from a prospective randomised study.

A few trials so far have evaluated the effectiveness of algorithms designed to calculate doses in oral anticoagulant therapy, with negative or contradictory results. We compared a genotype-guided algorithm vs physician management for the initiation of acenocoumarol. In a two-arm, prospective, randomised study with patients with atrial fibrillation who started therapy, the first dose was administered to all patients according to the physician's criteria. At 72 hours, the corresponding dose was calculated based on INR in the standard care group (SC, N=92), whereas genetic data (VKORC1, CYP2C9 and CYP4F2) were also considered for the genotype-guided dosing (pharmacogenetic) group (PGx, N=87) by using an algorithm previously validated in 2,683 patients. The primary outcomes were: patients with steady dose, the time needed to reach the same and the percentage of therapeutic INRs. After 90 days, 25% of the SC and 39% of the PGx patients reached the steady dose (p=0.038). Kaplan-Meier analysis showed that PGx group needed fewer days to reach therapeutic INR (p=0.033). Additionally, PGx had a higher percentage of therapeutic INRs than SC patients (50% and 45%, respectively) (p=0.046). After six months the proportion of steadily anticoagulated patients remained significantly higher in PGx (p=0.010). In conclusion, genotype-guided dosing was associated with a higher percentage of patients with steady dose than routine practice when starting oral anticoagulation with acenocoumarol.

Effect of VKORC1, CYP2C9 and CYP4F2 genetic variants in early outcomes during acenocoumarol treatment.

AIM: To analyze VKORC1, CYP2C9 and CYP4F2 polymorphisms in relation to the main outcomes in the first stages of acenocoumarol therapy. PATIENTS & METHODS: Nine hundred and forty one patients who had started therapy and in whom time to stable dosage, time to over-anticoagulation and adverse events occurred during 3 first months were retrospectively analyzed. RESULTS: VKORC1 AA patients needed fewer days to reach stable dosage (p = 0.017). International normalized ratio [INR] at 72 h, and VKORC1 and CYP2C9 genotypes conditioned INR values >2.5 (p < 0.001, p = 0.002 and p < 0.001, respectively), whereas CYP4F2 T carriers had a low risk of the same outcome (p = 0.009). In regards to combined genotypes, CYP4F2 had a significant effect on over-anticoagulation at the beginning of therapy except for the VKORC1 AA and CYP2C9*3 combination. CONCLUSION: In addition to VKORC1 and CYP2C9, CYP4F2 gene has a slight but significant role in reaching INR >2.5 during the first weeks of acenocoumarol therapy.