Stroke Prevention In Atrial Fibrillation Research Articles

Ten years of non-vitamin K antagonists oral anticoagulants for stroke prevention in atrial fibrillation: is warfarin obsolete?

Currently, four non-vitamin K antagonists oral anticoagulants (NOACs) are available for stroke prevention in atrial fibrillation (AF). These have been in clinical use for up to 10 years now. Besides data of the initial phase III clinical trials, now clinical data, several sub-studies, meta-analyses, and studies in special clinical settings and specific patient populations are available. This review shall give an overview on the history of NOAC development, sum up study data and ‘real-world’ clinical data as well as discuss several special clinical settings like NOAC treatment in patients that require coronary artery stenting or cardioversion (CV). Furthermore, treatment considerations in special patient populations like patients with renal impairment, obesity, or patients requiring NOACs for secondary prevention are discussed. The significance of NOAC treatment will be discussed under consideration of the recently published 2020 ESC/EACTS Guidelines for the diagnosis and management of AF.

Stroke prevention in atrial fibrillation: comparison of recent international guidelines.

Stroke prevention is one of the cornerstones of management in patients with atrial fibrillation (AF). As part of the ABC (Atrial fibrillation Better Care) pathway (A: Avoid stroke/Anticoagulation; B: Better symptom control; C: Cardiovascular risk and comorbidity optimisation), stroke risk assessment and appropriate thromboprophylaxis is emphasised. Various guidelines have addressed stroke prevention. In this review, we compared the 2017 APHRS, 2018 ACCP, 2019 ACC/AHA/HRS, and 2020 ESC AF guidelines regarding the stroke/bleeding risk assessment and recommendations about the use of OAC. We also aimed to highlight some unique points for each of those guidelines. All four guidelines recommend the use of the CHA2DS2-VASc score for stroke risk assessment, and OAC (preferably NOACs in all NOAC-eligible patients) is recommended for AF patients with a CHA2DS2-VASc score ≥2 (males) or ≥3 (females). Guidelines also emphasize the importance of stroke risk reassessments at periodic intervals (e.g. 4–6 months) to inform treatment decisions (e.g. initiation of OAC in patients no longer at low risk of stroke) and address potentially modifiable bleeding risk factors.

Stroke Prevention in Atrial Fibrillation

Ischemic strokes related to atrial fibrillation are highly prevalent, presenting with severe neurologic syndromes and associated with high risk of recurrence. Although advances have been made in both primary and secondary stroke prevention for patients with atrial fibrillation, the long-term risks for stroke recurrence and bleeding complications from antithrombotic treatment remain substantial. We summarize the major advances in stroke prevention for patients with atrial fibrillation during the past 30 years and focus on novel diagnostic and treatment approaches currently under investigation in ongoing clinical trials. Non–vitamin K antagonist oral anticoagulants have been proven to be safer and equally effective compared with warfarin in stroke prevention for patients with nonvalvular atrial fibrillation. Non–vitamin K antagonist oral anticoagulants are being investigated for the treatment of patients with atrial fibrillation and rheumatic heart disease, for the treatment of patients with recent embolic stroke of undetermined source and indirect evidence of cardiac embolism, and in the prevention of vascular-mediated cognitive decline in patients with atrial fibrillation. Multiple clinical trials are assessing the optimal timing of non–vitamin K antagonist oral anticoagulant initiation after a recent ischemic stroke and the benefit:harm ratio of non–vitamin K antagonist oral anticoagulant treatment in patients with atrial fibrillation and history of previous intracranial bleeding. Ongoing trials are addressing the usefulness of left atrial appendage occlusion in both primary and secondary stroke prevention for patients with atrial fibrillation, including those with high risk of bleeding. The additive value of prolonged cardiac monitoring for subclinical atrial fibrillation detection through smartphone applications or implantable cardiac devices, together with the optimal medical management of individuals with covert paroxysmal atrial fibrillation, is a topic of intensive research interest. Colchicine treatment and factor XIa inhibition constitute 2 novel pharmacologic approaches that might provide future treatment options in the secondary prevention of cardioembolic stroke attributable to atrial fibrillation.

Atrial fibrillation: villain or bystander in vascular brain injury.

Atrial fibrillation (AF) and stroke are inextricably connected, with classical Virchow pathophysiology explaining thromboembolism through blood stasis in the fibrillating left atrium. This conceptualization has been reinforced by the remarkable efficacy of oral anticoagulant (OAC) for stroke prevention in AF. A number of observations showing that the presence of AF is neither necessary nor sufficient for stroke, cast doubt on the causal role of AF as a villain in vascular brain injury (VBI). The requirement for additional risk factors before AF increases stroke risk; temporal disconnect of AF from a stroke in patients with no AF for months before stroke during continuous ECG monitoring but manifesting AF only after stroke; and increasing recognition of the role of atrial cardiomyopathy and atrial substrate in AF-related stroke, and also stroke without AF, have led to rethinking the pathogenetic model of cardioembolic stroke. This is quite separate from recognition that in AF, shared cardiovascular risk factors can lead both to non-embolic stroke, or emboli from the aorta and carotid arteries. Meanwhile, VBI is now expanded to include dementia and cognitive decline: research is required to see if reduced by OAC. A changed conceptual model with less focus on the arrhythmia, and more on atrial substrate/cardiomyopathy causing VBI both in the presence or absence of AF, is required to allow us to better prevent AF-related VBI. It could direct focus towards prevention of the atrial cardiomyopathy though much work is required to better define this entity before the balance between AF as villain or bystander can be determined.

Optimizing prognosis in atrial fibrillation: A call to action in Portugal

Atrial fibrillation (AF), the most common arrhythmia in the adult population worldwide, represents a significant burden in terms of cardiovascular mortality and morbidity and has repercussions on health economics. Oral anticoagulation (OAC) is key to stroke prevention in AF and, in recent years, results from landmark clinical trials of non-vitamin K oral anticoagulants (NOAC) have triggered a paradigm shift in thrombocardiology. Despite these advances, there is still a significant residual vascular risk associated with silent AF, bleeding, premature sudden death and heart failure.The authors review AF epidemiologic data, the importance of new tools for early AF detection, the current role of catheter ablation for rhythm control in AF, the state-of-the-art in periprocedural OAC, the optimal management of major bleeding, the causes of residual premature death and future strategies for improvements in AF prognosis.

Abstract 14763: Patients With a Perceived High-bleeding Risk in a Randomized Controlled Trial of Alert-based Computerized Decision Support for Stroke Prevention in Atrial Fibrillation: An Af-Alert Substudy

Introduction: A perceived increased risk of bleeding is one of the most frequent reasons for failure to prescribe anticoagulation for stroke prevention in atrial fibrillation (AF). We previously conducted a randomized controlled trial of alert-based computerized decision support (CDS) to increase prescription of antithrombotic therapy in 458 high-risk hospitalized patients with AF who were not being anticoagulated. Hypothesis: We hypothesized that patients with a perceived high risk for bleeding would have a similar HAS-BLED score and rate of major and clinically-relevant non-major bleeding. Methods: To determine the clinical characteristics and outcomes of these patients determined to be high-risk for bleeding, we analyzed the 248 patients in the alert group. Results: A perceived high risk of bleeding was the most common reason (77%) for omitting antithrombotic therapy. Median HAS-BLED scores were similar in these patients compared with those who were not deemed to have an increased bleeding risk (3 vs. 3, p=0.44). Despite being categorized as too high-risk for bleeding to receive antithrombotic therapy for stroke prevention at the time of the alert, nearly 12% of these patients were ultimately prescribed anticoagulation over the ensuing 90 days. The frequency of major and clinically-relevant non-major bleeding was similar between the two groups. Conclusions: In conclusion, a perceived high risk of bleeding was the most common reason for failure to prescribe antithrombotic therapy after the CDS alert. History of a prior bleeding event or underlying bleeding disorder was not reflected in a higher HAS-BLED score. Implementation of an alert-based CDS with specific attention to assessment of bleeding risk and mitigation warrants further study to encourage adherence to evidence-based clinical practice guideline recommendations for stroke prevention in AF.

Abstract 15396: Atrial Fibrillation Bleeding Risk and Prediction While Treated With Direct Oral Anticoagulants in Warfarin Naïve and Experienced Patients

Introduction: Direct oral anticoagulants (DOAC) are guideline-recommended over warfarin for stroke prevention in atrial fibrillation (AF). However, patients who are DOAC eligible are commonly maintained on warfarin. We sought to evaluate bleeding risk and prediction while on DOAC treatment (both for warfarin-naïve and -experienced patients) as compared to warfarin. Methods: We performed a retrospective cohort study using data from the Veteran Affairs health care system. We included patients with a prescription for warfarin and/or DOAC from 10/1/2010 to 9/30/2017 with an AF encounter in the 90 days prior to 30 days after prescription. We categorized DOAC treated patients as warfarin-naïve or -experienced and performed an on-treatment analysis to determine bleeding incidence and HAS-BLED score discrimination. In adjusted analyses, we compared risk of bleeding while treated with DOAC (both for warfarin-naïve and -experienced patients) to warfarin. Results: The analysis cohort included 99,143 patients treated with warfarin (71±10 years, HAS-BLED 2.6±1.2) and 73,732 and 26,760 patients treated with DOAC who were warfarin-naïve (74±10 years, HAS-BLED 2.4±1.0) and -experienced (71±9 years, HAS-BLED 2.8±1.1), respectively. DOAC patients with warfarin experience had more prior bleeds (DOAC, warfarin-experienced: 11.9%; DOAC, warfarin-naïve: 4.5%; warfarin: 6.2%; p<0.001 for both). Risk of intracranial bleeding was substantially lower while on DOAC treatment (both for warfarin-naïve and -experienced patients) as compared to warfarin ( Table ). HAS-BLED discrimination for bleeding outcomes, intracranial or any bleeding, was modest ( Table ). Conclusion: DOAC treatment had a favorable safety profile compared to warfarin treatment, even for DOAC treated patients with warfarin-experience who had more prior bleeds. These data argue against maintaining DOAC eligible patients on warfarin therapy regardless of HAS-BLED score.

Abstract 17474: End-Stage Renal Disease is Associated With Increased Complications From Watchman Implantation: A Propensity-Score Matched Analysis From National Readmission Database

Introduction: End-stage renal disease (ESRD) is associated with increased complications due to oral anticoagulation (OAC) use for stroke prevention in atrial fibrillation (AF). Left atrial appendage occlusion (LAAO) is indicated for patients who cannot tolerate or prefer not to use OAC but the outcomes of LAAO in ESRD has not been well studied. Methods: Using National Readmission Database January 2016-December 2017, we identified all adult AF patients who had LAAO performed in the months of January to November with no missing length of stay and/or mortality information. We excluded patients who had ablation, device implantation/revision, other form of LAAO and/or coronary artery bypass graft surgery performed during index hospitalization. 1:1 propensity score matching was performed for patients with and without ESRD based on variables shown in Table 1. The main outcome of interest was early mortality defined as mortality of index hospitalization or 30-day readmissions and index hospital complications. Results: A total of 13,790 procedures were included and of these 370 patients had history of ESRD. The baseline characteristics before and after matching are shown in table 1. After propensity score matching, ESRD group was associated with significantly higher early mortality, 30-day readmissions, systemic embolism and pericardial complications (Table 2). In the matched cohort, none of the patients had postprocedural cerebrovascular accident, transient ischemic attack, device thrombosis and device embolization. After propensity matching 2 (0.5%) developed acute kidney injury requiring hemodialysis. Conclusions: ESRD is associated with higher LOS, index hospital complications and early mortality from LAAO compared to patients without ESRD. Further studies comparing outcomes between OAC use and LAAO are warranted.

Association of adipocytokines serum levels with left atrial thrombus formation in atrial fibrillation patients on oral anticoagulation (Alert) – A cross-sectional study

Background and aimsOral anticoagulation is effective for stroke prevention in atrial fibrillation (AF). However, strokes may still occur in high-risk individuals. We conducted a prospective trial to assess the association between adipocytokine serum levels and surrogate parameters for thromboembolic events. Methods and resultsIn this cross-sectional multicenter trial, we enrolled 189 patients with AF who were on oral anticoagulation. The primary endpoint was defined as either the presence of spontaneous echo contrast (SEC), a left atrial appendage (LAA), or a left atrial (LA) thrombus on transesophageal echocardiography. We investigated the association of adipocytokine serum levels with the combined endpoint using logistic regression analysis. Forty-eight individuals (25%) were assigned to group 1 (G1) due to the occurrence of at least one of the components of the combined endpoint (41 [21.7%] SEC, 3 [1.6%] LA thrombus, 13 [6.9%] LAA thrombus), whereas the remaining patients formed group 2 (G2). The BMI, logarithmized (loge) leptin (G1: 2.0 ± 1.3 μg/ml, G2: 2.0 ± 1.1 μg/ml, p = 0.746) and visfatin serum levels (G1: 3.4 ± 0.3 ng/ml, G2: 3.4 ± 0.5 ng/ml, p = 0.900) did not significantly differ between the groups. Conversely, logarithmized adiponectin (G1: 3.3 ± 0.6 ng/ml, G2: 3.1 ± 0.7 ng/ml, p = 0.036) and resistin levels (G1: 1.8 ± 0.5 ng/ml, G2: 1.6 ± 0.5 ng/ml, p = 0.009) were higher in patients with the primary endpoint. Multivariate logistic regression analysis using a score that combined the individual adiponectin and resistin values in each patient corroborated this association. ConclusionsOur results suggest that adiponectin and resistin may act as potential biomarkers to identify individuals with AF who are at high thromboembolic risk.

The effect of computer decision support on optimizing appropriate dosing of novel oral anticoagulant therapy in the IMPACT-AF study

Abstract Background Guidelines favour use of the non-vitamin K oral anticoagulants (NOACs) over vitamin-K antagonists for stroke prevention in atrial fibrillation (AF). However, studies have shown these agents are being under-dosed relative to the doses recommended in the product labels. Purpose To assess the ability of a CDS tool, employed to support management of patients with AF in primary care, to optimize NOAC prescribing. Methods The Integrated Management Program Advancing Community Treatment of Atrial Fibrillation (IMPACT-AF) study was a cluster randomized controlled trial that assessed the ability of a CDS tool to optimize care of community-based AF patients. Between September 2014 and December 2016, 203 primary care providers (104 randomized to CDS use, 99 to usual care [UC]) and 1133 of their patients (n=597 CDS, n=548 UC) were enrolled. Among other functions, 9 CDS program rules provided recommendations on NOAC prescribing based upon a given patient's clinical profile, as per product labels. Appropriate NOAC prescribing within the IMPACT-AF study population was compared between patients managed with the CDS versus UC at baseline and 12-months. Results Of those patients prescribed a NOAC, a high proportion (approximately 70%) were managed as per NOAC prescribing recommendations at baseline (Fig. 1). At 12 months, this proportion did not appreciably change in the UC arm (Fig. 1). In the CDS arm, an 8.2% absolute/11.8% relative improvement in appropriate NOAC prescribing over baseline was seen at 12-months (Fig. 1). A comparison of patients at baseline and 12-months within each arm revealed a non-significant decline in the level of appropriate NOAC prescribing in the UC group (p=0.53). In the CDS arm, a significant improvement was observed in appropriate NOAC prescribing over time (p<0.001). Conclusion Even prior to any quality improvement efforts, appropriate NOAC prescribing was higher than anticipated in this contemporary cohort of community-based AF patients. At 12-months, significant further improvements were seen in the CDS but not the UC arm. These findings suggest that physician decision support can help enhance appropriate NOAC prescribing in the primary care setting. Figure 1. Appropriate NOAC prescribing Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Bayer Inc.

National trends of use of oral anticoagulants and severities of stroke among patients with atrial fibrillation

Abstract Background Underuse of oral anticoagulants (OACs) for stroke prevention in patients with atrial fibrillation (AF) is a common issue in the daily practice. The introduction of non-vitamin K antagonist OACs (NOACs) has changed the landscape of stroke prevention in AF. The goal of the present study was to investigate the trends of use of OACs and severities of stroke among AF patients using a nationwide AF database. Methods The present study used the Taiwan Nationwide Health Insurance Research Database (NHIRD). From year 2002 to 2015, a total of 66,331 AF patients aged >20 years who experienced ischemic stroke were identified from 447,259 AF patients. The temporal trends of use of OACs (either warfarin or NOACs) and the severities of stroke were analyzed. The estimated National Institutes of Health Stroke Scale (eNIHSS) calculated by 7-item NHIRD based stroke severity index, which has been validated before, was used to represent the stroke severities. Results The percentages of AF patients who were already anticoagulated when stroke occurred significantly increased from 20.3% in year 2002 to 40.5% in year 2015 (Figure A). The increment was more obvious in the era of NOACs (after year 2012 in Taiwan). In year 2015, NOACs accounts for around 69.6% of prescriptions of OACs. The mean eNIHSS gradually decreased from 17.3 (year 2002) to 14.3 (year 2015) (Figure B). Conclusions In the era of NOACs, the prescription rates of OACs significantly increased among AF patients who experienced ischemic stroke, temporally associated with a decrease in the stroke severity. Funding Acknowledgement Type of funding source: None

Left atrial appendage closure versus medical therapy in patients with atrial fibrillation: the APPLY study

Left atrial appendage closure (LAAC) with AMPLATZER occluders is used for stroke prevention in atrial fibrillation (AF). Net clinical benefit compared to medical therapy has not been tested. The aim of this study was to test whether long-term clinical outcome after LAAC with AMPLATZER occluders may be similar to medical therapy. Five hundred consecutive patients who underwent LAAC with AMPLATZER occluders were compared to 500 patients with medical therapy by propensity score matching. The primary efficacy endpoint was a composite of stroke, systemic embolism and cardiovascular/unexplained death. The primary safety endpoint consisted of major procedural adverse events and major bleedings. For assessment of net clinical benefit, all of the above-mentioned hazards were combined. After 2,645 patient-years at a mean follow-up of 2.7±1.5 years, the primary efficacy endpoint was reached by 75/1,342, 5.6% in the LAAC group versus 102/1,303, 7.8% per 100 patient-years (hazard ratio [HR] 0.70, 95% confidence interval [CI]: 0.53-0.95, p=0.026). The primary safety endpoint occurred in 48/1,342, 3.6% versus 60/1,303, 4.6% per 100 patient-years (HR 0.80, 95% CI: 0.55-1.18, p=0.21), and the combined hazard endpoint in 109/1,342, 8.1% versus 142/1,303, 10.9% per 100 patient-years (HR 0.76, 95% CI: 0.60-0.97, p=0.018). Patients receiving LAAC demonstrated lower rates of both all-cause and cardiovascular mortality (111/1,342, 8.3% vs 151/1,303, 11.6% per 100 patient-years [HR 0.72, 95% CI: 0.56-0.92, p=0.005] and 54/1,342, 4.0% vs 84/1,303, 6.5% per 100 patient-years [HR 0.64, 95% CI: 0.46-0.89, p=0.007]). LAAC with AMPLATZER devices showed a net clinical benefit over medical therapy by superior efficacy, similar safety and a benefit in all-cause and cardiovascular mortality.

Patients with perceived high-bleeding risk and computerized decision support for stroke prevention in atrial fibrillation: an AF-ALERT substudy : Piazza: outcomes of high-bleeding risk AF patients.

A perceived increased risk of bleeding is one of the most frequent reasons for withholding anticoagulation for stroke prevention in atrial fibrillation (AF). We previously conducted a randomized controlled trial of alert-based computerized decision support to increase prescription of anticoagulation in hospitalized patients with AF. To determine the clinical characteristics and outcomes of those patients whose inpatient health care providers received a computer alert, we analyzed all 248 patients in the alert group. Patients for whom providers elected to omit anticoagulation and provided a rationale of a perceived high risk of bleeding were compared with those who were not designated as high-risk. Perceived high risk of bleeding was the most common reason (77%) for omitting anticoagulation. Median HAS-BLED scores were similar in these patients compared with those who were not deemed to have an increased bleeding risk (3 vs. 3, p = 0.44). Despite being categorized as too high-risk for bleeding to receive antithrombotic therapy at the time of the alert, nearly 12% of these patients were ultimately prescribed anticoagulation by 90days. The frequency of major and clinically-relevant non-major bleeding was similar between the groups. The frequency of death, myocardial infarction, stroke, or systemic embolic event was similar in both groups (10.2% vs. 12.4%, p = 0.59). In conclusion, a perceived high risk of bleeding was the most common reason for omission of anticoagulation in patients with AF after a computerized alert. Perceived high risk of bleeding was not reflected in a higher HAS-BLED score.Clinical trial registration: ClinicalTrials.gov Identifier: NCT02339493 https://clinicaltrials.gov/ct2/show/NCT02339493 In a randomized controlled trial of computerized decision support to increase prescription of antithrombotic therapy in hospitalized patients with atrial fibrillation (AF), a perceived high risk of bleeding was the most common reason (77%) for omitting antithrombotic therapy after an on-screen alert. Median HAS-BLED scores were similar in these patients compared with those who were not deemed to have an increased bleeding risk (3 vs. 3, p = 0.44). Despite being categorized as too high-risk for bleeding to receive antithrombotic therapy for stroke prevention at the time of the alert, nearly 12% of these patients were ultimately prescribed anticoagulation over the ensuing 90days.

Adherence and the Moral Construction of the Self: A Narrative Analysis of Anticoagulant Medication.

In this article, we examine illness narratives to illuminate the discursive work that patients undertake to construct themselves as “good” and adherent. Biographical narrative interviews were undertaken with 17 patients receiving anticoagulation for stroke prevention in atrial fibrillation, from five English hospitals (May 2016–June 2017). Through pluralistic narrative analysis, we highlight the discursive tensions narrators face when sharing accounts of their medicine-taking. They undertake challenging linguistic and performative work to reconcile apparently paradoxical positions. We show how the adherent patient is co-constructed through dialogue at the intersection of discourses including authority of doctors, personal responsibility for health, scarcity of resources, and deservingness. We conclude that the notion of medication adherence places a hidden moral and discursive burden of treatment on patients which they must negotiate when invited into conversations about their medications. This discursive work reveals, constitutes, and upholds medicine-taking as a profoundly moral practice.

A prospective, observational study of rivaroxaban for stroke prevention in atrial fibrillation: the XANAP Korea.

Background/AimsAtrial fibrillation (AF)-related stroke accounts for 20% of ischemic strokes. Rivaroxaban use in AF patients for preventing stroke and systemic embolism was approved in 2013 in Korea. This study was to investigate the safety and effectiveness of rivaroxaban use in Korean patients with non-valvular AF in a real-world setting.MethodsThis was an analysis of the Korean patients in Xarelto for Prevention of Stroke in Patients with Atrial Fibrillation in Asia-Pacific (XANAP), which was a prospective, observational cohort study including patients with non-valvular AF starting rivaroxaban treatment to prevent stroke or non-central nervous system systemic embolism (non-CNS SE), conducted in 10 Asian countries.ResultsA total of 844 patients were enrolled in the Korean portion of the XANAP study. In XANAP Korea, the mean age was 70.1 years and 62.6% were males. The mean CHADS2 score was 2.5 and the mean CHA2DS2-VASc score was 3.8. 47% of the patients had experienced prior stroke or non-CNS SE or transient ischemic attack. 73.6% of the patients had CHADS2 score ≥ 2. Incidence proportions of 0.8% of the patients (1.1 per 100 patient-years) developed adjudicated treatment-emergent major bleeding. Death was observed in 1.2% of the patients. The incidence of non-major bleeding as well as thromboembolic event were 8.4% (11.6 per 100 patient-years) and 1.5% (2.0 per 100 patient-years), respectively.ConclusionsThis study reaffirmed the consistent safety profile of rivaroxaban. We found consistent results with overall XANAP population for rivaroxaban in terms of safety in non-valvular AF patients for the prevention of stroke and non-CNS SE.

Edoxaban for stroke prevention in atrial fibrillation in routine clinical care: 1-year follow-up of the prospective observational ETNA-AF-Europe study.

AimsNon-vitamin K oral anticoagulants are safe and effective for stroke prevention in patients with atrial fibrillation (AF). Data on the safety and efficacy of edoxaban in routine care are limited in Europe. We report 1-year outcomes in patients with AF treated with edoxaban in routine care.Methods and resultsETNA-AF-Europe is a prospective, multicentre, post-authorization, observational study enrolling patients treated with edoxaban in 10 European countries, the design of which was agreed with the European Medicines Agency as part of edoxaban’s post-approval safety plan. Altogether 13 092 patients in 852 sites completed the 1-year follow-up [mean age: 73.6 ± 9.5 years; 57% male, mean follow-up: 352 ± 49 days (median: 366 days)]. Most patients had associated comorbidities (mean CHA2DS2-VASc score: 3.1 ± 1.4). Stroke or systemic embolism was reported in 103 patients (annualized event rate: 0.82%/year), and major bleeding events were reported in 132 patients (1.05%/year). Rates of intracranial haemorrhage were low [30 patients (0.24%/year)]. Death occurred in 442 patients (3.50%/year); cardiovascular (CV) death occurred in 206 patients (1.63%/year). The approved dosing of edoxaban was chosen in 83%. All-cause and CV mortality were higher in patients receiving edoxaban 30 mg vs. 60 mg, in line with the higher age and more frequent comorbidities of the 30 mg group. Major bleeding was also numerically more common in patients receiving edoxaban 30 mg vs. 60 mg.ConclusionThe rates of stroke, systemic embolism, and major bleeding are low in this large unselected cohort of high-risk AF patients routinely treated with edoxaban.

Stroke Prevention in Atrial Fibrillation. Findings from the GLORIA-AF Registry

espanolIntroduccion: GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) es un registro internacional, prospectivo, en 3 fases, para determinar la seguridad y eficacia de dabigatran en pacientes con fibrilacion auricular no valvular recientemente diagnosticada en riesgo de stroke. La Fase 2 empezo cuando el dabigatran, el primer anticoagulante oral no vitamina K antagonista (NOAC) estuvo disponible. Objetivos: Describir los datos clinicos basales de la fase 2 en la poblacion general y el seguimiento a 2 anos de aquellos que recibieron dabigatran. Material y Metodos: Se incluyeron un total de 15644 pacientes de los cuales 15308 fueron elegibles y 4873 recibieron dabigatran. Se analizaron las caracteristicas de la Fibrilacion auricular, hallazgos en el seguimiento y las enfermedades concomitantes. Los datos fueron analizados usando estadisticas descriptivas. Resultados: Del total de pacientes elegibles, 45.5% eran mujeres, con una edad promedio de 71.0 (rango intercuartilo: 64, 78) anos. Los pacientes eran de Europa (47.9%), America del Norte (22.2%), Asia (20.1%), America Latina (6.0%), y Medio Oriente/Africa (3.9%). La mayoria se encontraba en alto riesgo de stroke (CHA2DS2-VASc score > 2; 86.1%); 13.9% tuvieron riesgo moderado (CHA2DS2-VASc > 1). En general, 80.3% recibieron anticoagulantes orales, de ellos 47.9% recibieron NOACs y 32.4% antagonistas de la vitamina K (VKA); 12.0% recibieron agentes antiagregantes plaquetarios y 7.6% no recibieron tratamiento antitrombotico. A 2 anos de seguimiento, el 70.5% permanecieron en dabigatran. Conclusiones: Los datos de la fase 2 del GLORIA-AF demostraron que en FA no valvular, los NOAC han sido ampliamente adoptados en la practica clinica, y fueron mas frecuentemente prescriptos que los VKA.No obstante una gran proporcion de pacientes en todo el mundo permanecieron sin tratamiento EnglishBackground: The Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF)is a multinational, prospective, 3-phase study to establish the safety and efficacy of dabigatran in patients with newly diagnosednonvalvular atrial fibrillation at risk of stroke. Phase II began when dabigatran, the first non-vitamin K antagonist oral anticoagulant(NOAC) became available.Objectives: The aim of this registry was to describe Phase II baseline clinical data in the general population and the 2-year follow-upof patients treated with dabigatran.Methods: Among 15,644 patients enrolled in the study, 15,308 were eligible and 4,873 received dabigatran. Atrial fibrillation characteristics,follow-up findings and concomitant diseases were recorded and analyzed using descriptive statistics.Results: Forty-five percent of eligible patients were women and median age was 71.0 years (interquartile range: 64-78 years). Patientswere from Europe (47.9%), North America (22.2%), Asia (20.1%), Latin America (6.0%), and the Middle East/Africa (3.9%).Most of them had high risk for stroke (CHA2DS2-VASc score ≥2; 86.1%) and 13.9% had moderate risk (CHA2DS2-VASc score=1). In80.3% of cases, patients received oral anticoagulants: 47.9% NOACs and 32.4% vitamin K antagonists (VKAs); 12.0% received antiplateletagents and 7.6% did not receive antithrombotic treatment. At the 2-year follow-up, 70.5% remained on dabigatran.Conclusions: Data from the GLORIA-AF Phase II registry showed that in nonvalvular AF, NOACs have been highly adopted in clinicalpractice, becoming more frequently prescribed than VKAs. Worldwide, however, a large proportion of patients have remainedundertreated.

Design and rationale of DUTCH-AF: a prospective nationwide registry programme and observational study on long-term oral antithrombotic treatment in patients with atrial fibrillation

IntroductionAnticoagulation therapy is pivotal in the management of stroke prevention in atrial fibrillation (AF). Prospective registries, containing longitudinal data are lacking with detailed information on anticoagulant therapy, treatment adherence and...

Letter by Nielsen and Søgaard Regarding Article, “Rivaroxaban Versus Apixaban for Stroke Prevention in Atrial Fibrillation: An Instrumental Variable Analysis of a Nationwide Cohort”

Letter by Nielsen and Søgaard Regarding Article, “Rivaroxaban Versus Apixaban for Stroke Prevention in Atrial Fibrillation: An Instrumental Variable Analysis of a Nationwide Cohort”

Use of real-world evidence in meta-analyses and cost-effectiveness models

Real-world evidence (RWE) provides external validity, supplementing and enhancing the randomized controlled trial data with valuable information on patient behaviors and outcomes, turning efficacy and safety results into real-world effectiveness and risks, but the use of RWE is associated with challenges. The objectives of this communication were to (1) summarize all guidance on how to conduct an RWE meta-analysis (MA) and how to develop an RWE cost-effectiveness model, (2) to describe our experience, challenges faced and solutions identified, (3) to provide recommendations on how to conduct such analyses. No formal guidelines on how to conduct an RWE MA or to develop an RWE cost-effectiveness model were identified. Using the context of non-vitamin K antagonist oral anticoagulants in stroke prevention in atrial fibrillation, we conducted an RWE MA, after having identified sources of uncertainty. We then implemented the results in an RWE cost-effectiveness model, defined as a model where all inputs come from RWE, including all parameters related to treatment effect. Based on challenges faced, our first recommendation relates to the necessity of conducting sensitivity analyses, either based on clinical or methodological considerations. Our second recommendation is the need for extensive collaboration with a wide range of experts, during the development of the analyses protocols, the implementation of the analyses and the interpretation of the results. RWE may address a number of gaps related to the treatment effect, and RWE economic evaluations for the treatment effect can provide extremely valuable insights into real-world economic value of interventions. As the increased recognition of the value of RWE could influence health technology assessment decision, and current practices, this communication supports the urgent need of more formal guidelines.