bluuebunny/crossref_metadata_2025_split huggingface dataset:
Edoxaban in atrial fibrillation with PCI by ACS or stable CAD presentation: a pre-specified analysis of the ENTRUST-AF PCI trial
Authors: Vranckx P , Valgimigli M , Eckardt L , Lewalter T , Laeis P , Reimitz P.E , Smolnik R , Zierhut W , Tijssen J , Goette A 
Published: November 2020

Abstract

Aim
We aimed to compare the safety and efficacy of edoxaban in combination with P2Y12 inhibition in the setting of percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF) presenting with an acute coronary syndrome (ACS) or stable coronary artery disease (SCAD).

Methods and results
This is a pre-specified sub-analysis of the ENTRUST-AF PCI trial. Participants were randomly assigned 1:1 to an edoxaban or vitamin K antagonist (VKA) based strategy and randomisation was stratified by ACS (edoxaban n=388, vitamin K n=389) vs. SCAD (edoxaban n=363, vitamin K=366). Participants received edoxaban 60mg once daily plus a P2Y12 inhibitor for 12 months; or VKA in combination with a P2Y12 inhibitor and aspirin 100mg (for 1–12 months).
The primary bleeding endpoint, a composite of International Society on Thrombosis and Haemostasis (ISTH) major or clinical relevant non-major bleeding, at 12 months occurred in 59 (18.52%/year) vs 79 (26.21%/year) ACS patients (Hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.591–1.018, P=0.0631), and in 69 (23.11%/year) vs 73 (25.02%/year) SCAD patients (HR 0.94, 95% CI 0.676–1.305, P=0.7082) with edoxaban and VKA based therapies, respectively (P for interaction [P-int]=0.2741).
The main efficacy endpoint (composite of cardiovascular death, myocardial infarction, stroke, systemic embolism, or definite stent thrombosis) occurred in 33 (9.59%/year) vs 28 (8.21%/year) ACS-patients (HR 1.16, 95% CI 0.697–1.916) compared with 16 (4.84%/year) vs 18 (5.47%/year) SCAD-patients (HR 0.91, 95% CI 0.465–1.781) with edoxaban and VKA based therapy, respectively (P-int=0.5573).

Conclusions
An antithrombotic regimen consisting of edoxaban and a P2Y12-inhibitor without aspirin provides equal safety and similar efficacy for ischaemic events in patients with AF regardless of their clinical presentation with ACS or SCAD.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH
Regular reassessment of bleeding risk using the HAS-BLED score reduces bleeding outcomes in a prospective cohort: a report from the mAFA II clinical trial extension
Authors: Guo Y , Lane D , Chen Y , Lip G.Y.H 
Published: November 2020

Abstract

Background
The HAS-BLED score was introduced to draw attention to modifiable bleeding risk factors and to identify patients with atrial fibrillation (AF) at high-risk of bleeding for early review and follow-up. The mAFA-II randomised trial reported that a holistic management strategy using App-based mobile Health technology support reduced AF-related adverse outcomes, compared to usual care.

Objective
To assess whether regular reassessment of bleeding risk using the HAS-BLED score would improve bleeding outcomes and oral anticoagulation (OAC) uptake.

Methods
Data for this analysis was drawn from the mAF App intervention arm. Bleeding risk (HAS-BLED score) and stroke risk (CHA2DS2-VASc score) were monitored prospectively using mAFA, and calculated during 4 periods: 1–30 days, 31–60 days, 61–180 days, and 181–365 days. Clinical events and OAC changes in relation to the dynamic monitoring and reassessments were analysed.

Results
We studied 1793 patients with AF (mean age 64 years, 32.5% female). The average number of re-assessments of CHA2DS2-VASc and HAS-BLED scores were 6.8 (SD 4.0) and 6.8 (4.1), respectively.
Comparing baseline and 12 months, the proportion of AF patients with HAS-BLED ≥3 decreased (11.8% vs. 8.5%, p=0.008), with changes in use of concomitant NSAIDs/antiplatelets, renal dysfunction, and labile international normalized ratio (INR) contributing to the decreased proportion of patients with HAS-BLED ≥3 temporally (p&lt;0.05). Use of non-vitamin K antagonist oral anticoagulants (NOAC), warfarin, and any antiplatelet drug was 47.1%, 13.8%, and 15.5%, respectively, at baseline.
Incident bleeding events decreased significantly from 1–30 days to 181–365 days (1.2% to 0.2%, respectively; Table 1). Warfarin and NOAC use increased significantly over this period (17.9% to 18.4% and 46.4% to 51.8%, respectively).

Conclusion
In this clinical trial cohort, dynamic risk monitoring and reassessment using the HAS-BLED score, together with holistic App-based management using mAFA II reduced bleeding events, addressed modifiable bleeding risks and increased uptake of OACs.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China (H2501), NIHR Global Health Research Group on Atrial Fibrillation management
Additive predictive power of the CHA2DS2-VASc and HAS-BLED scores for mortality in patients with atrial fibrillation
Authors: Morrone D , Kroep S , Ricci F , Renda G , Patti G , Kirchhof P , Chuang L.C , Van Hout B , De Caterina R 
Published: November 2020

Abstract

Background and objectives
In atrial fibrillation (AF), assessment of thromboembolic and bleeding risks are recommended to prescribe anticoagulation for stroke prevention. However, AF also increases mortality, and predictors of death are less characterized than predictors for stroke. We investigated the predictive power for mortality of the CHA2DS2-VASc, the HAS-BLED score and their combination.

Methods
Individual patient data were analyzed from the PREvention oF thromboembolic events-European Registry in Atrial Fibrillation (PREFER AF), a prospective real-world registry with a 12-month follow-up, with a total of 7243 patients enrolled from 461 hospitals and 7 European countries (Austria, France, Germany, Italy, Spain, Switzerland, and United Kingdom). Logistic regression was used to analyze the relationship of the CHA2DS2-VASc and HAS-BLED scores, and their combinations with outcome events, including mortality, at one year. The predictive ability of the scores was analyzed by comparing c-statistics.

Results
The study sample consisted of 5,209 AF patients with complete information on both scores. Mean age was 71.8±10.46 years; 3145 subjects (60.4%) were male. Events rate of stroke/SEE and major bleeding at one-year were 2.3% (122 patients) and 2.9% (149 patients), respectively. At one year, 3.1% of patients died (160 out of 5,209). Both scores had broadly similar c-statistics; for CHA2DS2-VASc: 0.637, 0.656 and 0.616 for models predicting mortality, SSE and major bleeding, respectively; for HAS-BLED: 0.620, 0.647, and 0.627, respectively. When including the individual components of both scores separately, c-statistics increased to 0.715, 0.694 and 0.636 with CHA2DS2-VASc, and to 0.681, 0.697 and 0.680 with HAS-BLED. The predictive power with both scores combined, removing overlapping components, was higher, with a c-statistic of 0.74, 0.73 and 0.70 for mortality (Table), SSE and major bleeding, respectively.

Conclusion
Both the CHA2DS2-VASc and the HAS-BLED score predict mortality similarly in AF, and a combination of the score components increases prediction significantly. Such combination may thus be clinically useful.

Funding Acknowledgement
Type of funding source: None
Different renal function estimation formulae and implications for dosing and clinical outcomes when prescribing non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation
Authors: Chao T.F , Chan Y.H , Kuo C.T , Chen S.A 
Published: November 2020

Abstract

Background
Pivotal randomized trials of non-vitamin K antagonist oral anticoagulants (NOACs) adopted Cockcroft-Gault (CG) formula to calculate estimated glomerular filtration rate (eGFR) to determine the dosages of NOACs. However, Modified Diet in Renal Disease (MDRD]) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulae are commonly used in clinical practice. In the present study, we investigated the agreements/disagreements of eGFRs calculated using different equations in Asian AF patients. Second, we studied the impacts of using different equations on the dosages of NOACs used, and finally, clinical outcomes compared to warfarin were assessed.

Methods
This retrospective study used medical data from a multicenter healthcare provider in Taiwan which included 39,239 AF patients whose data about body weight (BWs) and serum Creatinine (sCr) were available. Among these patients, there were 11,185 and 2,323 AF patients treated with NOACs and warfarin, respectively.

Results
At the cutoff values of eGFR of &lt;15 mL/min, 15–50 mL/min and &gt;50 mL/min, the agreements were 78% between MDRD and CG, and 81% between CKD-EPI and CG. The disagreements between different equations were largely due to over-estimations (21% for MDRD and 17% for CKD-EPI), especially for patients aged &gt;75 years and BWs &lt;50kg (58.8% for MDRD and 50.9% for CKD-EPI). For patients treated with NOACs, around 7.6% (MDRD) and 6.5% (CKD-EPI) had dosages of NOACs that were discordant compared to using the CG equation, with the highest percentages for rivaroxaban (11–13%) and lowest for edoxaban (1%).
Among patients receiving NOACs whose dosages were defined as “on-label” based on MDRD or CKD-EPI, only those whose dosages were “truly on-label” based on CG were associated with a lower risk of ischemic stroke/systemic embolism (IS/SE) (adjusted hazard ratio [aHR] 0.78, 95% CI 0.61–1.00), major bleeding (aHR 0.34, 95% CI 0.26–0.45) and IS/SE or major bleeding (aHR 0.55, 95% CI 0.46–0.66) compared to warfarin (Figure). The risk of IS/SE (aHR 0.82, 95% CI 0.39–1.72), major bleeding (aHR 0.57, 95% CI 0.25–1.32) and IS/SE or major bleeding (aHR 0.69, 95% CI 0.40–1.19) were similar between warfarin and patients treated with NOACs whose dosages were disconcordant between eGFRs calculated using MDRD and CG (Figure).

Conclusions
The adoptions of MDRD or CKD-EPI rather than CG would result in inappropriate dosing of NOACs (mainly overdosing) which would attenuate the advantages of NOACs compared to warfarin. Therefore, the CG equation should be used as the “gold standard” for the calculations of eGFRs to guide the NOAC dosages.

Funding Acknowledgement
Type of funding source: None
Risk factors of major bleeding in elderly atrial fibrillation patients from the ANAFIE registry
Authors: Inoue H , Yamashita T 
Published: November 2020

Abstract

Background
Bleeding is associated with shorter life expectancy during anticoagulant treatment in atrial fibrillation (AF) patients. Prior studies showed bleeding during anticoagulant treatment occurred more frequently in elderly AF patients than in younger AF patients. HAS-BLED score is a risk assessment tool for bleeding. However, since it was developed from the database of patients with warfarin, it has not been clarified whether this score is applicable in the era of direct oral anticoagulant (DOACs), especially for elderly AF patients.

Purpose
All Nippon AF In the Elderly (ANAFIE) registry was designed to obtain real-world information regarding patients with non-valvular AF (NVAF) aged ≥75 years, including current status of anticoagulant therapy and prognosis. The present study aimed to determine factors that associate with major bleeding for elderly NVAF patients using the dataset of ANAFIE registry conducted in Japan.

Methods
Total of 32,099 patients aged ≥75 years with NVAF were enrolled in ANAFIE registry, and followed for 2 years. Incidence rates of major bleeding for total population, &lt;85 years old group and ≥85 years old group were estimated using Kaplan-Meier method. Cox proportional hazards model was used to determine independent predictors of major bleeding. The factors included in the model were selected by backward elimination procedure.

Results
Mean age was 81.5 years. 23,738 (74.0%) was &lt;85 years old and 8,361 (26.0%) was ≥85 years old. 92.5% of whole population used anticoagulants including warfarin (27.6%) or DOACs (72.3%). Major bleeding occurred in 279 patients at 12 months with 189 in &lt;85 years and 90 in ≥85 years old group. The cumulative incidence rate of major bleeding at 12 months by Kaplan-Meier method was 0.9% in whole patients, and was slightly higher in ≥85 years than in &lt;85 years old group (1.1% vs 0.8%). In multivariate analysis of the whole patients, history of major bleeding (hazard ratio [HR]: 2.17), severe hepatic dysfunction (HR: 3.62), malignancy (HR: 1.52), falling within a year (HR: 2.07), antiplatelet use (HR: 1.37) and warfarin use (HR: 1.81) emerged as independent predictors of major bleeding. Severe hepatic dysfunction (HR: 9.17), HbA1c &lt;6.0% (HR: 2.19) and dementia (HR: 2.00) were associated with major bleeding in patients only in aged ≥85 years. On the other hand, proton pump inhibitor use (HR: 1.36), creatinine clearance &lt;30 mL/min (HR: 1.53) and polypharmacy (HR: 1.61) were associated with major bleeding only in those aged &lt;85 years.

Conclusion
Among elderly (≥75 years old) Japanese NVAF patients in the era of DOACs, prior major bleeding, severe hepatic dysfunction, malignancy, falling within a year, antiplatelet use and warfarin use were identified as independent predictors of major bleeding. Impact of some predictors differed between the 2 age groups (&lt;85 years vs ≥85 years).

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Daiichi Sankyo Co., Ltd.
Comparison of warfarin, dabigatran, rivaroxaban and apixaban for effectiveness and safety among elderly patients with atrial fibrillation: a nationwide cohort study
Authors: Rutherford O.C.W , Jonasson C , Ghanima W , Soderdahl F , Halvorsen S 
Published: November 2020

Abstract

Introduction
Age is a strong independent risk factor for stroke and systemic embolism (SE) in patients with atrial fibrillation (AF). Reducing risk of stroke/SE with oral anticoagulation (OAC) in elderly patients involves a correspondingly greater risk of bleeding than in younger patients. Non-vitamin K antagonist oral anticoagulants (NOACs) are associated with a net clinical benefit over vitamin K antagonists in the elderly population, but knowledge is lacking about the comparative effectiveness and safety between specific oral anticoagulants in these patients.

Purpose
The aim of this study was to compare the rates of stroke/SE and major bleeding between new users of warfarin, dabigatran, rivaroxaban, and apixaban, in a nationwide cohort of AF patients over 75 years.

Methods
From Norwegian national registries we identified all anticoagulant naïve initiators of warfarin, dabigatran, rivaroxaban and apixaban over 75 years of age between January 2013 and December 2017. During follow-up, patients were censored upon switching OAC, discontinuation of OAC, death, or end of study period. Multivariate competing risk regression was used to evaluate association between treatment and the outcomes stroke/se and major bleeding, treating death as a competing risk.

Results
A total of 30 401 patients were identified; 6 650 starting warfarin, 3 857 starting dabigatran, 6 108 starting rivaroxaban, and 13 786 starting apixaban. The median age was 82 years. Dabigatran-users had less comorbidity than all other OAC-users; the greatest difference was seen in the proportion of patients with chronic kidney disease (4.3% in the dabigatran-group versus 7.0%, 10.5%, and 16.5% in the rivaroxaban, apixaban, and warfarin groups, respectively). The median follow-up time was 15 months, during which time 1 386 (4.6%) patients suffered a stroke/SE; 1 277 (4.2%) patients had a major bleeding episode; and 3 270 (10.8%) died. Adjusted subhazard ratios for stroke/SE and major bleeding are presented in the figure.

Conclusion
Comparing NOACs with warfarin, we found no significant differences in risk of stroke/SE, while apixaban was associated with lower risk of major bleeding than warfarin. Comparing NOACs with each other; dabigatran was associated with a significantly lower risk of stroke/SE compared with rivaroxaban and apixaban, while both dabigatran and apixaban were associated with significantly lower risks of major bleeding compared with rivaroxaban.
Incidence rates and subhazard ratios

Funding Acknowledgement
Type of funding source: Public hospital(s). Main funding source(s): South-Eastern Norway regional Health Authority
Edoxaban treatment of elderly patients with atrial fibrillation in routine clinical practice: 1-year results of the non-interventional Global ETNA-AF program
Authors: Yamashita T , Wang C.C , Kim Y.-H , De Caterina R , Kirchhof P , Reimitz P , Chen C , Unverdorben M , Koretsune Y 
Published: November 2020

Abstract

Background
The prevalence of atrial fibrillation (AF) and the need for appropriate anticoagulation increase with age. The benefit/risk profile of direct oral anticoagulants such as edoxaban in elderly population with AF in regular clinical practice is therefore of particular interest.

Purpose
Analyses of Global ETNA-AF data were performed to report patient characteristics, edoxaban treatment, and 1-year clinical events by age subgroups.

Methods
Global ETNA-AF is a multicentre, prospective, noninterventional program conducted in Europe, Japan, Korea, Taiwan, and other Asian countries. Demographics, baseline characteristics, and 1-year clinical event data were analysed in four age subgroups.

Results
Of 26,823 patients included in this analysis, 50.4% were ≥75 years old and 11.6% were ≥85 years. Increase in age was generally associated with lower body weight, lower creatinine clearance, higher CHA2DS2-VASc and HAS-BLED scores, and a higher percentage of patients receiving the reduced dose of 30 mg daily edoxaban. At 1-year, rates of ISTH major bleeding and ischaemic stroke were generally low across all age subgroups. The proportion of intracranial haemorrhage within major bleeding events was similar across age groups. All-cause mortality increased with age more than cardiovascular mortality.

Conclusion
Data from Global ETNA-AF support the safety and effectiveness of edoxaban in elderly AF patients (including ≥85 years) in routine clinical care with only a small increase in intracranial haemorrhage. The higher all-cause mortality with increasing age is not driven by cardiovascular causes.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Daiichi Sankyo
Contemporary procedural trends of Watchman percutaneous left atrial appendage occlusion in the United States: insight from the National Inpatient Sample
Authors: Munir M.B , Khan M.Z , Han F.T , Reeves R , Hsu J.C 
Published: November 2020

Abstract

Background/Introduction
Left atrial appendage occlusion with the Watchman device has emerged as a viable therapy for stroke risk mitigation in atrial fibrillation (AF) patients.

Purpose
To determine trends in real-world utilization and in-hospital adverse events from Watchman implantation since its approval by the Food and Drug Administration (FDA) in 2015.

Methods
This was a retrospective cohort study utilizing data from National Inpatient Sample for calendar years 2015–2017. Watchman procedures were identified using ICD-9-CM and ICD-10-CM codes of 37.90 and 02L73DK, respectively. The outcomes assessed were associated complications and in-hospital mortality. Trends analysis were performed using analysis of variance.

Results
A total of 17,700 patients underwent Watchman implantation during the study period. There was a significantly increased trend in the number of Watchman procedures performed over the study years (from 1,195 in 2015 to 11,165 devices in 2017, p&lt;0.01). A significant decline in the rate of complications (from 26.4% in 2015 to 7.9% in 2017, p&lt;0.01) and inpatient mortality (from 1.3% in 2015 to 0.1% in 2017, p&lt;0.01) were noted.

Conclusion
Since its introduction, the Watchman procedure appears to be increasingly more common and safe in the management of stroke risk in patients with AF.
Trends in mortality over years

Funding Acknowledgement
Type of funding source: None
A pro-thrombotic left atrial haemodynamic profile is present in older individuals with cardiovascular risk factors even without atrial fibrillation
Authors: Spartera M , Stracquadanio A , Pessao-Amorim G , Von Ende A , Ferreira V , Hess A.T , Neubauer S , Wijesurendra R.S , Casadei B 
Published: November 2020

Abstract

Background
Atrial fibrillation (AF), by inducing left atrial (LA) stasis and thrombus formation, is a major cause of ischaemic embolic stroke. However, up to 25% of embolic strokes occur in the absence of AF or any other identifiable mechanism. We hypothesised that exposure to risk factors leads to a prothrombotic LA haemodynamic profile, with a consequent risk of thrombus formation and embolic stroke even in sinus rhythm (SR).

Purpose
To quantify the relative effects of AF and risk factors on LA function and haemodynamics in three groups: (1) patients with persistent AF before and after cardioversion, (2) patients in SR with no history of AF who were matched to AF patients for stroke risk, and (3) healthy controls.

Methods
Ninety-five participants were recruited: 37 AF patients scheduled for cardioversion [median CHA2DS2-VASc = 2 (1.5–3.5); median age 69 years], 35 matched non-AF patients [median CHA2DS2-VASc 3 (2.0–4.0); median age 69 years], and 23 healthy subjects [median CHA2DS2-VASc 0 (0–0); median age 33 years]. Advanced cardiovascular MRI was used to assess LA function and 4D flow.

Results
Patients with persistent AF displayed significantly lower LA emptying fraction (LAEF), reservoir strain, and peak blood flow velocities compared to both control groups in SR, as well as profound alterations in atrial blood flow patterns and vortex volume ratio (all p&lt;0.001 vs both control groups). In the 65% of patients who were in SR at ≥4 weeks post cardioversion, all LA parameters were significantly improved (all paired p&lt;0.001 vs baseline scan in AF; red vs blue in Figure 1), but LA haemodynamics were now no longer different from those in matched non-AF patients (all p=ns; blue vs green in Figure 1 C-D). However, both AF patients cardioverted to SR and matched non-AF patients had significantly impaired LA function (LA EF and LA reservoir strain) and LA haemodynamics (lower peak velocity and higher vortex volume ratio), compared to heathy controls (all p&lt;0.01; blue/green vs grey in Figure 1).

Conclusions
We found evidence of a gradient of LA haemodynamic dysfunction, where the most marked phenotype was seen in patients scanned in AF, but with significant abnormalities remaining after restoration of SR in AF patients, and intriguingly, also present to a similar degree in matched non-AF patients. Advanced atrial imaging offers the potential to select patients with an adverse pathophysiological substrate directly predisposing to LA thrombus formation for future clinical trials of anticoagulation in SR.
Figure 1

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): NIHR Oxford Biomedical Research Centre