bluuebunny/crossref_metadata_2025_split huggingface dataset:
P4758Label adherence of non-vitamin K antagonist oral anticoagulants and clinical outcomes in patients with atrial fibrillation: A nationwide study
Authors: Yu H T , Yang P S , Jang E , Kim T H , Uhm J S , Kim J Y , Pak H N , Lee M H , Joung B , Lip G Y H 
Published: October 2019

Abstract

Background
Dose adjustment of non-vitamin K antagonist oral anticoagulants (NOACs) is indicated in some patients with atrial fibrillation (AF), based on selected patient factors or concomitant medications.

Purpose
We assessed the frequency of label adherence of NOAC dosing among AF patients and the associations between off-label NOAC dosing and clinical outcomes in real-world clinical practice.

Methods
We evaluated 53,649 AF patients treated with a NOAC using Korean National Health Insurance Service database during the period from January 2013 to December 2016. NOAC doses were classified as either underdosed or overdosed, consistent with U.S. Food and Drug Administration labeling. Cox proportional hazards regression was performed to investigate the effectiveness and safety outcomes including stroke or systemic embolism, major bleeding, and all-cause mortality.

Results
Overall, 16,757 NOAC-treated patients (31.2%) were underdosed, 4,492 were overdosed (8.4%), and 32,400 (60.4%) were dosed appropriately according to drug labeling. Compared with patients with label adherence, those who were underdosed or overdosed were older (71±8 and 75±7 years of age vs. 70±9 years of age, respectively; p<0.001), more likely female (39% and 53% vs. 38%, respectively; p<0.001), and had higher CHA2DS2-VASc scores (4.6±1.7 and 5.3±1.7 vs. 4.5±1.8, respectively; p<0.001). NOAC overdosing was associated with increased risk for stroke or systemic embolism (5.76 vs. 4.03 events/100 patient-years, p<0.001), major bleeding (4.77 vs. 2.94 events/100 patient-years, p<0.001), and all-cause mortality (5.43 vs. 3.05 events/100 patient-years, p<0.001) compared with label-adherent use.
Figure 1

Conclusion
In routine clinical practice, a significant proportion (almost 2 in 5) of AF patients received NOAC doses inconsistent with drug labeling. NOAC overdosing is associated with increased risk for stroke or systemic embolism, major bleeding, and all-cause mortality in Asian patient with AF.
P4760New minimally invasive and tailor-made strategy for cryoballoon ablation in patients with paroxysmal atrial fibrillation
Authors: Nakano T , Suenari K , Suruga K , Takemoto H , Hashimoto Y , Tomomori S , Higaki T , Ooi K , Dai K , Nakama Y , Kawase T , Nishioka K , Otsuka M , Masaoka Y , Shiode N 
Published: October 2019

Abstract

Background
Currently, cryoballoon ablation (CBA) has proven to be highly effective in achieving free from atrial fibrillation (AF), especially paroxysmal AF. However, the optimal freezing protocol for each patient to achieve successful pulmonary vein isolation by only CBA is still uncertain. The aim of this study was to evaluate the clinical implications of a reduction in the freezing duration (<180s) during CBA guided by the time to target temperature.

Methods
From November 2015 to August 2018, 286 consecutive paroxysmal AF patients undergoing CBA were enrolled. We compared 107 patients undergoing a tailor-made CBA procedure (Group A; August 2017-August 2018) to 179 patients with a standard CBA procedure (Group B; November 2015–July 2017). In Group A, the freezing duration was reduced to 150s when the temperature reached ≤−40°C within 40s. Furthermore, we reduced it to 120s when it reached ≤−50°C within 60s. In the other patients, the freezing time was 180s except for excessive freezing over −60°C and/or emergent situations while monitoring the esophageal temperature and for phrenic nerve injury as in Group B.

Results
The baseline clinical characteristics were similar between two groups. In Group A, 89 patients (83%) underwent CBA with a reduction in the freezing time. The rate of having reduction time in left inferior PV (LIPV) and right inferior PV (RIPV) was lower compared with left superior PV (LSPV) and right superior PV (RSPV) (respectively 17%, 29%, 56%, and 63.5%). However, for right inferior PV, in 31 patients having the reduced freezing time, none of them required touch-up ablation. Although the procedure time and frequency of touch-up ablation did not differ between the 2 groups, total freezing time for each PV was significantly shorter in Group A than Group B as shown in figure (LSPV: 164±28s vs. 216±67s; p<0.001, LIPV: 187±44s vs. 218±69s; p<0.001, RSPV: 147±31s vs. 192±51s; p<0.001, RIPV: 180±50 vs. 218±73s; p<0.001). The AF free survival rate during the follow-up period (356±167 days) was similar between the 2 groups (log-rank test, p=0.38). Furthermore, the complication rate was similar 2 groups.
The freezing time for each PV

Conclusion
The safety and efficacy of the new tailor-made CBA strategy were non-inferior to the standard procedure. This study showed that the unnecessary freezing time could be reduced in most of paroxysmal AF patients.
P4769Optimal rivaroxaban dose in Asian patients with atrial fibrillation and normal or mildly impaired renal function
Authors: Choi E.-K , Lee S R , Han K D , Jung J H , Oh S , Lip G Y H 
Published: October 2019

Abstract

Background
Although rivaroxaban 15 mg was only given to patients with creatinine clearance (CrCl) <50mL/min in the pivotal clinical trial, this dose has been commonly prescribed in Asian patients with non-valvular atrial fibrillation (AF) regardless of renal function. There is a paucity of information regarding the clinical outcomes of rivaroxaban 15 mg compared to rivaroxaban 20 mg in patients with CrCl ≥50mL/min. This study aimed to examine the effectiveness and safety of two doses of rivaroxaban in Asian patients with AF and CrCl ≥50mL/min.

Methods
Using the Korean National Health Insurance Service database, patients with AF and normal or mildly impaired renal function (CrCl ≥50mL/min) and naïve to rivaroxaban or warfarin were included from January 2014 to December 2016. Three separate 1:1 propensity score-matched cohorts were conducted: rivaroxaban 20 mg (R20) vs. warfarin (n=15,584), rivaroxaban 15 mg (R15) vs. warfarin (n=11,554), and R20 vs. R15 (n=10,392). Hazard ratios (HRs) for ischemic stroke, intracranial hemorrhage (ICH), gastrointestinal (GI) bleeding, major bleeding, all-cause death, and composite clinical outcome were analyzed.

Results
Among the pooled total study population, mean age was 66.9±10.9 years, 62.2% were male, mean CHA2DS2-VASc score was 3.16±1.79, and mean CrCl was 83.6±42.0 mL/min (median 78.4 mL/min, IQR 67.7–91.0 mL/min). A substantial proportion (42.6%) of patients with CrCl ≥50 mL/min were prescribed off-label R15 for stroke prevention in the Korean AF population. Compared to warfarin, both R20 and R15 showed significantly lower risk for ischemic stroke, major bleeding (mainly through reduction of ICH), and all-cause death (Figure). Overall, both R20 and R15 had better results for the composite clinical outcome compared to warfarin (HR: 0.617, 95% CI: 0.550–0.691 for R20, and HR: 0.759, 95% CI: 0.675–0.853 for R15). Compared to off-label R15, on-label R20 showed a nonsignificant trend toward lower risks of ischemic stroke, hospitalization for GI bleeding, hospitalization for major bleeding, and all-cause death. Overall, on-label R20 had better results for the composite clinical outcome compared to off-label R15 in patients with CrCl ≥50 mL/min (HR: 0.852, 95% CI: 0.735–0.988). This benefit was consistently observed in patients aged ≥80 years and those <50 kg. In patients with CrCl 50–60 mL/min, R20 showed a nonsignificant trend toward a higher risk of hospitalization for major bleeding compared to R15 (HR: 1.828, 95% CI 0.994–3.452).

Conclusions
Among Asians with AF and CrCl ≥50mL/min, both R20 and R15 were associated with reduced risk of ischemic stroke, ICH, major bleeding, and all-cause death without significantly increased risk of GI bleeding compared with warfarin. In patients with CrCl ≥50mL/min, on-label R20 showed better results for the composite clinical outcome compared to off-label R15.
P4772Role of anticoagulation in patients with subclinical AF and its association with cardiovascular events: a SILENT sub study
Authors: Martinelli Filho M , Siqueira S F , Athayde G A T , Dias K M , Pinheiro A O , Oliveira C P , Souza A L , Jorge C H D , Pedrosa A A A , Teixeira R A , Nishioka S A D 
Published: October 2019

Abstract

Background
Atrial fibrillation (AF) is a well-established thromboembolic event risk factor. Episodes of subclinical AF (SCAF) recorded in implantable electronic cardiac devices (IECD) have been related to clinical AF and increased risk of stroke. However, there is no scientific evidence regarding the role of anticoagulation in this population. Objective: Our objective is to assess the association of SCAF with clinical AF and rate of systemic thromboembolic events, in a short-term follow-up.

Methods
This is a sub-study of SILENT, a prospective, randomized, unicentric study which included patients with sinus rhythm, IECD, with CHA2DS2-VASc ≥2, without previous history of AF. Patients were randomized to the Intervention Group and to the Control Group in the 1: 1 ratio. Patients of the Intervention Group with SCAF episodes (>6 min) received anticoagulation, as well as those with clinical AF in both groups. The primary end point was systemic thromboembolic phenomena and the secondary endpoints were SCAF rate, total and cardiovascular mortality, cardiovascular hospitalization and bleeding.

Results
A total of 758 patients were evaluated, with a mean age of 72.81 years (± 9.73), of which 461 (60.8%) were female. The mean follow-up was 19.59±4.24 months. Baseline characteristics were similar in both groups. Only 3 patients presented the primary outcome (two of them from Intervention Group). There were 16 deaths (2,1%) and 44 cardiovascular hospitalizations (5,8%), with no difference between groups. Atrial high rate episodes (AHRE) and clinical AF were more prevalent in Control Group, leading to an equal rate of anticoagulation between groups. Clinical AF was statistically associated to previous atrial high rate episodes of any duration (p=0.001) and correlated with SCAF (p<0.01 and R: 0,60) previously recorded in the device.

Conclusion
This sub study showed that, in a short term follow-up, SCAF has a good correlation with clinical AF occurrence with low rate of thromboembolic events. The Silent study will evaluate in an extended population the role of anticoagulation, in the long term.

Acknowledgement/Funding
None
P4776Age-dependent anti-thrombotic therapy for atrial fibrillation patients with intermediate risk (CHA2DS2-VASc Score of 1 or 2) of ischemic stroke
Authors: Lee K M , Kim M H , Choi S Y , Kim S J , Kim S W , Park J S 
Published: October 2019

Abstract

Background
Although older age is one of the most important risk factor for stroke in atrial fibrillation (AF), it is unclear whether oral anticoagulants are beneficial for AF patients with intermediate CHA2DS2-VASc score (1 for male or 2 for female) according to age threshold. We sought to investigate the effect of age-dependent antithrombotic therapy for ischemic stroke in Korean intermediate risk AF patients.

Methods
We enrolled 29,592 patients (males with CHA2DS2-VASc score of 1 and females with CHA2DS2-VASc score of 2) using the Korean National Health Insurance Service database. The clinical endpoint was the occurrence of ischemic stroke. The propensity score matching method was used to balance covariates across treated and untreated patients.

Results
Treated male AF patients were 6,570 (67.1%) with age <55 years, 7,115 (70.9%) with 55–64 years and 6,470 (68.3%) with 65–74 years in each age risk criterion. Also, treated female AF patients were 3,156 (71.3%) with age <55 years, 2,838 (71.0%) with 55–64 years and 3,440 (72.6%) with 65–74 years in each age risk criterion. Among male and female patients (age <55 years and 55–64 years) with 1 risk factor, an annual ischemic stroke rate was not significantly different between treated and untreated patients at full follow-up. However, treated AF patients who are in age 65–74 year without other risk factor had a much lower annual risk of ischemic stroke [(1.05%/year (male) and 1.04%/year (female)] compared with untreated patients [(1.77%/year (male) (p<0.026) and 1.86%/year (female) (p<0.041).

Conclusions
Age is an important predictor in determining the risk of ischemic stroke in AF patients with intermediate CHA2DS2-VASc scores (1 for male or 2 for female). We suggest that the benefit of anti-thrombotic therapy for intermediate risk AF patients depends on age threshold.
P4783Treatment persistence of patients with atrial fibrillation on VKA or NOAC: Data from GLORIA-AF Phase III 1-year interim analysis
Authors: Lip G Y H , Diener H.-C , Dubner S J , Halperin J L , Rothman K J , Ma C.-S , Lu S , Paquette M , Riou Franca L , Zint K , Teutsch C , Huisman M V 
Published: October 2019

Abstract

Background
Oral anticoagulation (OAC) persistence is important for optimizing stroke prevention in patients with atrial fibrillation (AF); non-vitamin K oral anticoagulants (NOACs) generally show better persistence than vitamin K antagonists (VKAs), while the impact of dosing regimens remains unclear. We compared treatment persistence of NOACs and VKAs, and of NOAC dosing regimens in the prospective GLORIA-AF registry program.

Methods
Patients newly diagnosed with AF were enrolled in Phase III of GLORIA-AF (2014–2016) from 4 geographical regions (North America [NA], Europe, Asia and Latin America). Treatment persistence after 1 year for i) NOAC (dabigatran, rivaroxaban, apixaban, edoxaban) vs VKA, and ii) twice daily (bid, dabigatran, apixaban) vs once daily (od; rivaroxaban, edoxaban) NOAC treatment was analysed using multivariable Cox analysis; propensity score trimming was used to reduce bias due to unmeasured confounders. Missing data was handled by multiple imputation.

Results
Overall, 21,592 patients were enrolled (4970 [23%] patients on VKAs, 12,797 [59%] on NOACs, 2391 [11%] on antiplatelets, and 1426 [6.6%] received no therapy; 8 [0.04%] received other treatment). After trimming, 11,935 and 4484 patients treated with NOACs and VKAs, respectively, were compared. NOACs had better treatment persistence than VKAs (discontinuation hazard ratio [HR]=0.75, 95% confidence interval [CI] 0.69–0.81). Other relevant associations were decreased OAC persistence for symptomatic AF, NA and Asia regions (Table). There was no difference in treatment persistence for patients on a bid (N=7842) vs od (N=4098) NOAC (discontinuation HR=0.94, 95% CI 0.86–1.02).

Conclusion
In this 1-year interim analysis of GLORIA-AF Phase III, treatment persistence was improved with NOACs vs VKAs, whereas for NOACs, dosing regimen (bid vs od) had no impact on treatment persistence.

Acknowledgement/Funding
The GLORIA-AF Registry program was funded by Boehringer-Ingelheim
P4785Clinical characteristics and 1-year outcomes in atrial fibrillation patients with or without history of intracranial haemorrhage treated with edoxaban: snapshot analysis of the Global ETNA-AF program
Authors: Kirchhof P , Unverdorben M , Koretsune Y , Wang C C , Kim Y H , Brueggenjuergen B , Lee B C , Levy P , Rauer H , Reimitz P E , Yamashita T , De Caterina R 
Published: October 2019

Abstract

Background
Patients with atrial fibrillation (AF) who survive an intracranial haemorrhage (ICH) are at high risk of stroke, death, and recurrent haemorrhage. Effectiveness and safety of the nonvitamin K antagonist oral anticoagulant (NOAC) edoxaban in this patient population has not been reported.

Purpose
This snapshot analysis from the global ETNA-AF program compared 1-year outcomes in AF patients with and without history of ICH treated with edoxaban from Europe, Japan, and Korea/Taiwan.

Methods
Global ETNA-AF (EU: NCT02944019, Japan: UMINehz745.116117011, Korea/Taiwan: NCT02951039) is a multinational, multicentre, prospective, noninterventional program of AF patients receiving edoxaban in regular clinical care. Demographics, baseline characteristics, and outcomes at 1-year follow-up were reported for 19416 patients with and without a history of ICH.

Results
Of the 19416 patients, 297 had a history of ICH. At 1-year follow-up, incidences of International Society on Thrombosis and Haemostasis (ISTH) major bleeding (including ICH) and clinically relevant nonmajor bleeding (CRNMB) were generally low. The rate of ischaemic stroke was higher in patients with a history of ICH than in those without prior ICH.
Europe (N=7672) Korea/Taiwan (N=1701) Japan (N=10043) History of ICH, n (%) Yes No Yes No Yes No 36 (0.5) 636 (99.5) 27 (1.6) 1674 (98.4) 234 (2.3) 9809 (97.7) Age, median (IQR) 75 (69, 78) 74 (68, 80) 70 (66, 76) 72 (66, 77) 76 (71, 82) 75 (68, 81) Gender, male % 72.2 57.4 70.4 59.9 60.7 59.3 Weight, median (IQR) kg 80.0 (75.0, 88.0) 80.0 (70.0, 92.0) 68.0 (54.0, 77.0) 65.0 (58.0, 73.0) 57.0 (50.0, 65.0) 59.0 (51.0, 68.0) CHA2DS2-VASc, mean (SD) 4.2 (1.44) 3.1 (1.38) 3.9 (1.63) 3.0 (1.43) 4.0 (1.56) 3.4 (1.64) HAS-BLED, mean (SD) 4.3 (1.23) 2.6 (1.12) 3.9 (1.55) 2.4 (10.7) 3.7 (1.07) 2.3 (1.12) CrCl [mL/min], median (IQR) 70.5 (58.8, 85.1) 70.4 (53.8, 90.1) 63.7 (45.8, 84.2) 61.6 (48.4, 78.1) 58.5 (46.0, 73.2) 60.2 (46.1, 77.0) Edoxaban 60/30 mg, % 83.3 / 16.7 77.1 / 22.9 55.6 / 44.4 50.2 / 49.8 21.8 / 78.2 27.8 / 72.2 1-year outcome, n (%/year)   Major bleeding (ISTH) 2 (5.94) 66 (0.92) 0 (0) 13 (0.82) 3 (1.92) 66 (0.96)   Intracranial haemorrhage 1 (2.91) 19 (0.26) 0 (0) 5 (0.32) 1 (0.64) 18 (0.26)   Major GI* bleeding 0 (0.00) 20 (0.28) 0 (0) 2 (0.13) 2 (1.28) 30 (0.43)   CRNMB 0 (0.00) 102 (1.43) 0 (0) 11 (0.70) 6 (3.82) 219 (3.20)   Ischaemic stroke 1 (2.93) 41 (0.57) 1 (4.04) 11 (0.70) 4 (2.57) 78 (1.13) *Gastrointestinal.

Conclusion
Our data underpin the need for effective stroke prevention. In AF patients with a history of ICH, data suggest that edoxaban can be safely and effectively administered in patients with and without prior ICH in regular clinical care.

Acknowledgement/Funding
Daiichi Sankyo
P4788One-year outcomes of elderly patients with atrial fibrillation: snapshot data from the global noninterventional program on edoxaban treatment in routine clinical practice in atrial fibrillation
Authors: Wang C C , Kim Y H , Brueggenjuergen B , De Caterina R , Kirchhof P , Lee B C , Levy P , Rauer H , Reimitz P E , Unverdorben M , Yamashita T , Koretsune Y 
Published: October 2019

Abstract

Background
As populations age, prevalence of atrial fibrillation (AF) and ensuing need for oral anticoagulation increase. Benefits and risks of nonvitamin K antagonist oral anticoagulants such as edoxaban in the frail, elderly population with AF in regular clinical care is of special interest.

Purpose
Data from Global ETNA-AF capturing almost 2ehz745.1164 patients treated with edoxaban in Europe, Japan, and Korea/Taiwan, was analyzed to compare outcomes in patients <75 years, elderly (≥75 years), and very elderly (≥85 years) patients.

Methods
Global ETNA-AF is a multinational, multicentre, prospective, noninterventional program (EU: NCT02944019, Japan: UMINehz745.116417011, Korea/Taiwan: NCT02951039). Demographics, baseline characteristics, and 1-year outcome data were reported for 19416 patients classified into 3 age categories.

Results
At 1-year follow-up, rates of major bleeding (including intracranial haemorrhage [ICH]) and ischaemic stroke were generally low. All-cause and CV mortality increased with age; CV mortality was a minor proportion of all-cause mortality in all age groups. Rates of major bleeding and ischaemic stroke increased slightly with age, but to a lesser extent than all-cause and CV mortality. There was no increase in the rate of ICH with age.
<75 yrs (N=9725) ≥75 yrs (N=9687) ≥85 yrs (N=2186) Age, median (IQR) 68.0 (63.0, 72.0) 80.0 (77.0, 84.0) 87.0 (86.0, 89.0) Gender, male % 65.8 51.5 41.4 BMI, median (IQR) 25.6 (22.9, 29.0) 24.5 (21.9, 27.5) 23.4 (20.8, 26.1) Weight, median (IQR) kg 71.0 (60.0, 84.5) 62.5 (52.9, 75.0) 55.4 (47.6, 67.0) CHA2DS2-VASc, mean (SD) 2.4 (1.28) 4.1 (1.27) 4.4 (1.34) CrCl [mL/min], median (IQR) 78.4 (63.6, 95.9) 52.0 (41.1, 64.5) 40.3 (32.2, 49.4) Edoxaban 60/30 mg, % 64.0/36.0 34.3/65.7 15.8/84.2 1-year outcome, n (%/year)   Major bleeding (ISTH) 57 (0.71) 93 (1.19) 25 (1.53)   Intracranial hemorrhage 22 (0.27) 22 (0.28) 3 (0.18)   Major GI* bleeding 18 (0.22) 36 (0.46) 16 (0.98)   CRNMB** 126 (1.57) 212 (2.73) 56 (3.45)   Ischaemic stroke 53 (0.66) 83 (1.06) 23 (1.41)   All-cause/CV mortality 95 (1.18)/25 (0.31) 224 (2.86)/55 (0.70) 89 (5.44)/23 (1.41) *Gastrointestinal. **Clinically relevant nonmajor bleeding.

Conclusion
Global data from this set of unselected patients support the use of edoxaban as a safe and effective treatment in elderly and very elderly patients with AF in regular clinical care.

Acknowledgement/Funding
Daiichi Sankyo
P4792Dabigatran versus vitamin K antagonists in patients with atrial fibrillation and valvular heart disease
Authors: Strange J E , Sindet-Pedersen C , Staerk L , Grove E L , Gerds T A , Torp-Pedersen C , Gislason G H , Butt J H , Fosboel E L , Olesen J B 
Published: October 2019

Abstract

Background
Atrial fibrillation (AF) and valvular heart disease (VHD) are both associated with an increased risk of stroke. Outside post-hoc analyses of randomized controlled trials, knowledge on the effectiveness and safety of dabigatran in patients with AF and VHD is scarce.

Objectives
To compare the risk of all-cause mortality, stroke, and bleeding in patients with AF and VHD treated with dabigatran or a vitamin K antagonist (VKA).

Methods
All Danish residents are provided a unique personal identification number enabling cross-linking of data from Danish nationwide registries. We identified all patients with AF and VHD initiating treatment with dabigatran or VKA between the 22nd of August 2011 and the 31st of December 2014. We defined VHD as aortic stenosis/regurgitation, mitral regurgitation, bioprosthetic heart valves, mitral-, and aortic valve repair. Outcomes were all-cause mortality, stroke, and bleeding. 2-year standardized absolute risks were calculated from cause-specific Cox regression models with death as competing risk.

Results
In total, 599 (27.3%) and 1,596 (72.7%) patients initiated treatment with dabigatran and VKA. The 2-year standardized absolute risk of all-cause mortality (95% CI) for VKA was 27.6% (25.1% to 30.1%) and 25.4% (21.8% to 29.0%) for dabigatran with a corresponding absolute risk difference of −2.2% (−6.3% to 1.9%) (Figure 1). The 2-year standardized absolute risk of stroke for VKA was 3.4% (2.3% to 4.5%) and 3.9% (2.2% to 5.5%) for dabigatran with a corresponding absolute risk difference of 0.5% (−1.6% to 2.5%). Lastly, the 2-year standardized absolute risk of bleeding for VKA was 8.2% (6.6% to 9.7%) and 7.6% (5.1% to 10.1%) for dabigatran with a corresponding absolute risk difference of −0.5% (−3.4% to 2.4%).
Figure 1

Conclusions
In this nationwide cohort study, we found no significant difference in the risk of all-cause mortality, stroke, or bleeding in patients with AF and VHD when comparing VKA to dabigatran.