Direct oral anticoagulants for stroke prevention in patients with device-detected atrial fibrillation: assessing net clinical benefit.

Subclinical, device-detected atrial fibrillation (AF) is frequently recorded by pacemakers and other implanted cardiac rhythm devices. Patients with device-detected AF have an elevated risk of stroke, but a lower risk of stroke than similar patients with clinical AF captured with surface electrocardiogram. Two randomized clinical trials (NOAH-AFNET 6 and ARTESiA) have tested a direct oral anticoagulant (DOAC) against aspirin or placebo. A study-level meta-analysis of the two trials found that treatment with a DOAC resulted in a 32% reduction in ischaemic stroke and a 62% increase in major bleeding; the results of the two trials were consistent. The annualized rate of stroke in the control arms was ∼1%. Several factors point towards overall net benefit from DOAC treatment for patients with device-detected AF. Strokes in ARTESiA were frequently fatal or disabling and bleeds were rarely lethal. The higher absolute rates of major bleeding compared with ischaemic stroke while on treatment with a DOAC in the two trials are consistent with the ratio of bleeds to strokes seen in the pivotal DOAC vs. warfarin trials in patients with clinical AF. Prior research has concluded that patients place a higher emphasis on stroke prevention than on bleeding. Further research is needed to identify the characteristics that will help identify patients with device-detected AF who will receive the greatest benefit from DOAC treatment.

Heart Failure Events After Long-term Continuous Screening for Atrial Fibrillation: Results From the Randomized LOOP Study.

BACKGROUND: Mounting evidence indicates that even device-detected subclinical atrial fibrillation is associated with a higher risk of heart failure (HF). However, the potential impact of atrial fibrillation screening on HF remains unknown. METHODS: The LOOP Study (Atrial Fibrillation detected by Continuous ECG Monitoring using Implantable Loop Recorder to prevent Stroke in High-risk Individuals) evaluated the effects of atrial fibrillation screening on stroke prevention using an implantable loop recorder (ILR) versus usual care in elderly individuals with additional stroke risk factors. In this secondary analysis, we explored the following HF end points: (1) HF event or cardiovascular death; (2) HF event; (3) event with HF with reduced ejection fraction (HFrEF); and (4) HFrEF event or cardiovascular death. Outcomes were assessed in a Cox model both as time-to-first events and as total (first and recurrent) events analyzed using the Andersen-and-Gill method. RESULTS: Of 6004 participants (mean age 74.7 and 52.7% men), 1501 were randomized to ILR screening and 4503 to the control group. In total, 77 (5.1%) in the ILR group versus 295 (6.6%) in the control group experienced the primary outcome of an HF event or cardiovascular death. Compared with usual care, ILR screening was associated with a nonsignificant reduction in the primary outcome for the time-to-first event analysis (hazard ratio, 0.78 [95% CI, 0.61-1.01]) and the total event analysis (hazard ratio, 0.77 [95% CI, 0.59-1.01]). Similar results were obtained for the HF event. A significant risk reduction in total events was observed in the ILR group for the composite of HFrEF event or cardiovascular death and for HFrEF event (hazard ratio, 0.74 [95% CI, 0.56-0.98] and 0.65 [95% CI, 0.44-0.97], respectively). CONCLUSIONS: In an elderly population with stroke risk factors, ILR screening for atrial fibrillation tended to be associated with a lower rate of total HF events and cardiovascular death, particularly those related to HFrEF. These findings should be considered hypothesis-generating and warrant further investigation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02036450.

Severe aortic stenosis treated with transcatheter aortic valve implantation or surgical aortic valve replacement with Perimount in Western Denmark 2016-2022: a nationwide retrospective study.

OBJECTIVES: The healthcare registries in Denmark present a unique opportunity to gain novel insights into the outcomes associated with both transcatheter and surgical approaches to aortic valve replacement. Our objective is to enhance shared decision-making by comparing long-term mortality and clinical outcomes between treatments. METHODS: This observational study included all patients with severe aortic stenosis undergoing elective isolated transfemoral transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR) in Western Denmark between January 2016 and April 2022. Patient population and clinical data were identified from the Western Danish Heart Registry and the National Danish Patient Registry, respectively. A propensity score-matched population was generated. Outcomes were investigated according to Valve Academic Research Consortium-3. RESULTS: A total of 2269 TAVI patients and 1094 SAVR patients where identified. The propensity score-matched population consisted of 468 TAVI patients (mean[SD]age, 75.0[5.3] years) and 468 SAVR patients (mean[SD] age, 75.1[4.6]years). The Kaplan-Meier estimate for the 5-year all-cause mortality was 29.8% in the TAVI group and 16.9% for in the SAVR group (P = 0.019). The risk of all stroke or transient ischaemic attack after five year was 15.1% in the TAVI group and 11.0% in the SAVR group (P = 0.047). CONCLUSIONS: This study underscores the importance of evaluating all patient factors when choosing an aortic valve replacement method. Surgical aortic valve replacement was an excellent choice, especially for patients with New York Heart Association class I/II, ≥75 age, left ventricular ejection fraction ≥50%, or longer life expectancy.

Recurrent Ischemic Stroke in Patients With Atrial Fibrillation While Receiving Oral Anticoagulants.

Importance: Patients with atrial fibrillation (AF) can have an ischemic stroke (IS) despite oral anticoagulant (OAC) treatment. Knowledge regarding the association between OAC discontinuation and the subsequent risk of recurrent IS in patients with AF is limited. Objectives: To determine the risk of recurrent IS in patients with AF receiving OAC and to evaluate the association between OAC discontinuation and the risk of recurrent IS. Design, Setting, and Participants: This is a nationwide cohort study of patients aged 50 years or older in Denmark who had AF and an IS (entry IS) and were initiating or restarting subsequent OAC treatment after being discharged between January 2014 and December 2021. Patients were followed up for recurrent IS until June 2022. Within this study cohort, a nested case-control analysis was performed in which patients with recurrent IS were matched to patients receiving OAC who had not yet experienced a stroke. Data were analyzed from May 25, 2023, to April 18, 2024. Exposure: Use of OAC at the time of recurrent IS or the equivalent date in matched controls based on redeemed prescriptions. Main Outcomes and Measures: The primary outcome was recurrent IS. Crude and adjusted cumulative incidences of recurrent IS and all-cause mortality were calculated in cohort analyses, and adjusted odds ratios (aORs) were determined for recurrent IS associated with OAC discontinuation in nested case-control analyses. Results: The study cohort included 8119 patients (4392 [54.1%] male; mean [SD] age, 78.4 [9.6] years; median (IQR) CHA2DS2-VASc score, 4.0 [3.0-5.0]). Over a mean (SD) follow-up of 2.9 (2.2) years, 663 patients had a recurrent IS, of whom 533 (80.4%) were receiving OAC at the time of their recurrent IS. The crude cumulative incidence of recurrent IS at 1 year was 4.3% (95% CI, 5.9%-7.1%), and the crude cumulative incidence of all-cause mortality was 15.4% (95% CI, 14.7%-16.2%). Adjusted analysis showed similar results. Patients who discontinued OACs had a higher risk of recurrent IS (89 cases [13.4%], 180 controls [6.8%]; aOR, 2.13; 95% CI, 1.57-2.89) compared with patients still receiving OAC. Conclusions and Relevance: The risks of recurrent IS and mortality were high in patients with AF despite secondary prevention with OAC, and OAC discontinuation doubled the risk of recurrent IS compared with patients who continued OAC. This finding highlights the importance of OAC continuation and the need for improved secondary stroke prevention in patients with AF.

Is interventional technique better than the traditional over-the-wire method for left ventricular lead implantation in cardiac resynchronization therapy?

Background: Interventional cardiac resynchronization therapy (I-CRT) for left ventricular lead (LVL) placement works as a supplement to traditional (over-the-wire) cardiac resynchronization therapy (T-CRT). It has been argued that I-CRT is a time-consuming and complicated procedure. Objective: The purpose of this study was to investigate differences in procedure-related, perioperative, postoperative, and clinical endpoints between I-CRT and T-CRT. Methods: This single-center, retrospective, cohort study included all consecutive patients receiving a CRT-pacemaker/defibrillator between January 1, 2012, and August 31, 2018. Patients underwent T-CRT from January 1, 2012, to June 1, 2015, and I-CRT from January 1, 2016, to August 31, 2018. We obtained data from patient record files, fluoroscopic images, and the Danish Pacemaker and ICD Register. Data were analyzed using Wilcoxon rank-sum/linear regression for continuous variables and the Pearson χ2/Fisher exact for categorical variables. Results: Optimal LVL placement was achieved in 82.7% of the I-CRT group and 76.8% of the T-CRT group (P = .015). In the I-CRT group, 99.0% of LVLs were quadripolar vs 55.3% in the T-CRT group (P <.001). Two or more leads were used during the procedure in 0.7% and 10.5% of all cases in the I-CRT and T-CRT groups, respectively (P <.001). Total implantation time was 81.0 minutes in the I-CRT group and 83.0 minutes in the T-CRT group (P = .41). Time with catheters in the coronary sinus was 45.0 minutes for the I-CRT group vs 37.0 minutes in the T-CRT group, respectively (P <.001). Conclusion: I-CRT did not prolong total implantation time despite longer time with catheters in the coronary sinus. I-CRT allowed more optimal LVL placement, wider use of quadripolar leads, and use of fewer leads during the procedure.

No Detectable Differences in microRNA Plasma Levels between Diabetic Hypertensive Patients with and without Incident Subclinical Atrial Fibrillation.

Background: Long-term rhythm monitoring (LTRM) can detect undiagnosed atrial fibrillation (AF) in patients at risk of AF and stroke. Circulating microRNAs (miRNAs), which have been shown to play a role in atrial electrical and structural remodelling, could help to select patients who would benefit most from LTRM. The aim of this study was to investigate whether patients with diabetes mellitus (DM) and hypertension and screen-detected subclinical AF (SCAF) using an insertable cardiac monitor (ICM) have significantly different plasma baseline levels of five selected miRNAs playing a role in the modulation of atrial electrical and structural remodelling (miR-21-5p, miR-29b-3p, miR-150-5p, miR-328-3p, and miR-432-5p) compared to those without SCAF. Methods: This study was performed at the outpatient clinic of a secondary academic teaching hospital between December 2013 and November 2015. Eligible patients were ≥65 years of age with DM and hypertension but without known heart diseases. All patients received an ICM. On the day of ICM implantation, blood samples for the measurement of plasma levels of the five miRNAs were drawn. In this post hoc analysis, we investigated their expression by reverse transcription-quantitative polymerase chain reaction. MiRNA plasma levels in patients with and without newly detected SCAF were compared. Results: We included 82 consecutive patients (median age of 71.3 years (IQR 67.4-75.1)), who were followed for a median of 588 days (IQR: 453-712 days). Seventeen patients (20.7%) had ICM-detected SCAF. Plasma levels of miR-328-3p, miR-29b-3p, miR-21-5p, miR-432-5p, and miR-150-5p were slightly but not significantly different in patients with incident SCAF compared with patients without. Conclusions: In patients with hypertension and DM, newly detected SCAF was not significantly associated with changes in expression levels of miR-21-5p, miR-29b-3p, miR-150-5p, miR-328-3p, and miR-432-5p.

A call for action to include psychosocial management into holistic, integrated care for patients with atrial fibrillation.

Contemporary management of atrial fibrillation (AF) has become increasingly complex. Therefore, strong efforts have been made during the past decade to develop models for structured, integrated care for patients with AF. These have also been incorporated in international guidelines for the management of patients with AF. However, implementation of integrated care approaches in daily clinical practice is scarce and far from optimal, and it may require a re-thinking of the structure of the healthcare system. The reasons for the poor implementation are many, from limited time and economic resources to deficits in postgraduate education of healthcare professionals, lack of involvement of patients in how integrated care should be designed, and fragmentation of the healthcare system. Moreover, patients' psychological challenges, which not only impact patients' adherence to treatment but, if untreated, increase their risk of morbidity, mortality, and poor quality of life, are not given sufficient attention. It is time to start a necessary discussion of what integrated care should be, what it should contain, and what is necessary to implement it in daily clinical practice.

Left Atrial Strain Predicts Subclinical Atrial Fibrillation Detected by Long-term Continuous Monitoring in Elderly High-Risk Individuals.

BACKGROUND: Left atrial (LA) speckle tracking provides detailed information on atrial function. Its utility for predicting subclinical atrial fibrillation (SCAF) is unclear. Therefore, we sought to investigate whether LA strain measures could predict SCAF detected by long-term continuous rhythm monitoring. METHODS: This was an echocardiographic substudy of the LOOP study, where elderly at risk of stroke were randomized to receive a loop recorder (Reveal LINQ) or control. Participants who received a loop recorder were included in this analysis. Echocardiography included LA reservoir, conduit, and contraction strain. Participants were followed with continuous rhythm monitoring for SCAF (≥6 minutes). Cox proportional hazards regression was applied to adjust for atrial fibrillation risk factors. RESULTS: In total, 956 participants were eligible for analysis. Median continuous rhythm monitoring was 35 months (IQR, 20-40 months), during which 278 (29%) were diagnosed with SCAF. The mean age was 74 years, 56% were male, median CHA2DS2-VASc-score was 4. LA reservoir strain was an independent predictor of SCAF after multivariable adjustments (HR, 1.04 [1.02-1.05], per 1% decrease) and so was contraction strain. The findings were unchanged in competing risk analyses and in participants with normal LA size and diastolic function. Participants with low reservoir strain (<33%) had a significantly higher risk of SCAF compared with those with high reservoir strain (incidence rate, 14.5 [12.4-16.9] versus 9.8 [8.2-11.8] events/100 person-years). The same was noted for low versus high contraction strain. CONCLUSIONS: LA reservoir and contraction strain are independent predictors of SCAF in elderly at risk of stroke. This also applies to individuals with normal LA size and diastolic function. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02036450.

The ABC-Stroke Risk Score and Effects of Atrial Fibrillation Screening on Stroke Prevention: Results From the Randomized LOOP Study.

BACKGROUND: The ABC-stroke score is a risk scheme for prediction of stroke or systemic embolism (SE) in atrial fibrillation (AF). This study sought to examine whether the score could be useful in predicting stroke in AF-naïve individuals and risk stratifying for AF screening. METHODS AND RESULTS: The LOOP (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-Risk Individuals) study randomized 6004 AF-naïve individuals aged 70 to 90 years with stroke risk factors to either screening with an implantable loop recorder and anticoagulation upon detection of new-onset AF episodes ≥6 minutes, or usual care. A total of 5781 participants had available ABC-stroke score at baseline and were included in this secondary analysis: 4170 (72.1%) with an estimated stroke/SE risk ≤1%/year versus 1611 (27.9%) with an estimated stroke/SE risk >1%/year. Having an annual ABC-stroke risk >1% was associated with stroke/SE, stroke/SE/cardiovascular death, and all-cause death (hazard ratio, 1.82 [95% CI, 1.44-2.21], 2.17 [95% CI, 1.80-2.62], and 2.19 [95% CI, 1.87-2.56], respectively). For screening with implantable loop recorder versus usual care, no significant reduction in these study outcomes was obtained in any ABC-stroke risk groups (P>0.0500 for all), with no signal toward interaction (Pinteraction>0.2500 for all). Similar findings were yielded when assessing the ABC-stroke score as a continuous variable. CONCLUSIONS: In an elderly, AF-naïve population with additional stroke risk factors, a higher ABC-stroke score could identify individuals with increased stroke risk. However, this risk score may not be useful in pinpointing those more likely to benefit from AF screening and subsequent preventive treatment. These findings should be considered as hypothesis generating and warrant further study. REGISTRATION: URL: https://www.clinicaltrials.gov; unique identifier: NCT02036450.

Anticoagulation-Associated Bleeding in Patients Screened for Atrial Fibrillation versus Usual Care-A Post Hoc Analysis from the LOOP Study.

Background Atrial fibrillation (AF) prevalence is rising; however, data on the bleeding risks associated with the detection of subclinical AF are needed. Objective Our objective was to determine the bleeding increment associated with implantable loop recorder (ILR) screening for subclinical AF and subsequent anticoagulation initiation compared with usual care. Methods This post hoc study utilized LOOP trial data from 6,004 elderly patients with stroke risks randomized to either ILR ( n = 1,503) or usual care ( n = 4,503). The mean follow-up time was 64.5 months, and none were lost to follow-up. The primary exposure was the initiation of oral anticoagulation, and the main outcome was the risk of major bleeding events following initiation of oral anticoagulants (OACs), determined by time-dependent cox regression. Second, we investigated antithrombotic prescription patterns and major bleeding events after antiplatelet treatment and in subgroups. Results OAC was initiated in 1,019 participants with a mean age (years) of 78.8 (± 4.67) in control versus 77.0 (± 4.84) in ILR, p < 0.0001. Altogether did 202 participants end or pause OAC treatment. Among AF patients (n = 910) had 40 (28%) completely ended OAC and 105 (72%) temporarily paused OAC during follow-up. Major bleeding events totaled 221 (3.7%). Forty-seven major bleeding events followed an OAC initiation in 1,019 participants (4.6%); 26 versus 21 events in the control and ILR groups, respectively. The hazard ratio (HR) for major bleeding after OAC initiation compared with before initiation was 2.08 (1.50-2.90) p < 0.0001 overall, 2.81 (1.82-4.34) p < 0.0001 for control and 1.32 (0.78-2.23) p = 0.31 for the ILR group ( p = 0.07 for interaction). Antiplatelet treatment resulted in an overall adjusted HR of 1.3 (0.96-1.75) p = 0.09. For OAC users aged ≥75 years in the ILR group, the rate of major bleeding was 1.73 (0.92-2.96) compared with 0.84 (0.36-1.66) for an age <75 years, and the rate of the corresponding control subgroup aged ≥75 years was 2.20 (1.23-3.63) compared with 1.64 (0.82-2.93) for an age <75 years. Conclusion The individual risk of major bleeding increased twofold after initiation of oral anticoagulation for all patients in this study. However, the patients screened for subclinical AF did not have a higher bleeding risk after initiation of anticoagulation compared with those in usual care. Trial Registration: The LOOP study is registered at ClinicalTrials.gov, identifier: NCT020364 50.

Epicardial adipose tissue and subclinical incident atrial fibrillation as detected by continuous monitoring: a cardiac magnetic resonance imaging study.

Epicardial adipose tissue (EAT) has endocrine and paracrine functions and has been associated with metabolic and cardiovascular disease. This study aimed to investigate the association between EAT, determined by cardiac magnetic resonance imaging (CMR), and incident atrial fibrillation (AF) following long-term continuous heart rhythm monitoring by implantable loop recorder (ILR). This study is a sub-study of the LOOP study. In total, 203 participants without a history of AF received an ILR and underwent advanced CMR. All participants were at least 70 years of age at inclusion and had at least one of the following conditions: hypertension, diabetes, previous stroke, or heart failure. Volumetric measurements of atrial- and ventricular EAT were derived from CMR and the time to incident AF was subsequently determined. A total of 78 participants (38%) were diagnosed with subclinical AF during a median of 40 (37-42) months of continuous monitoring. In multivariable Cox regression analyses adjusted for age, sex, and various comorbidities, we found EAT indexed to body surface area to be independently associated with the time to AF with hazard ratios (95% confidence intervals) up to 2.93 (1.36-6.34); p = 0.01 when analyzing the risk of new-onset AF episodes lasting ≥ 24 h. Atrial EAT assessed by volumetric measurements on CMR images was significantly associated with the incident AF episodes as detected by ILR.

Anticoagulation with edoxaban in patients with long atrial high-rate episodes ≥24†h.

BACKGROUND AND AIMS: Patients with long atrial high-rate episodes (AHREs) ≥24 h and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared with no anticoagulation in these patients. METHODS: This secondary pre-specified analysis of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes (NOAH-AFNET 6) trial examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared with placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and electrocardiogram (ECG)-diagnosed atrial fibrillation. RESULTS: Median follow-up of 2389 patients with core lab-verified AHRE was 1.8 years. AHRE ≥24 h were present at baseline in 259/2389 patients (11%, 78 ± 7 years old, 28% women, CHA2DS2-VASc 4). Clinical characteristics were not different from patients with shorter AHRE. The primary outcome occurred in 9/132 patients with AHRE ≥24 h (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). Atrial high-rate episode duration did not interact with the efficacy (P-interaction = .65) or safety (P-interaction = .98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE ≥24 h developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; P < .001). CONCLUSIONS: This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk.

The Danish Atrial Fibrillation Registry: A Multidisciplinary National Pragmatic Initiative for Monitoring and Supporting Quality of Care Based on Data Retrieved from Administrative Registries.

Aim: The Danish Atrial Fibrillation (AF) Registry monitors and supports improvement of quality of care for all AF patients in Denmark. This report describes the registry's administrative and organizational structure, data sources, data flow, data analyses, annual reporting, and feedback between the registry, clinicians, and the administrative system. We also report the selection process of the quality indicators and the temporal trends in results from 2017-2021. Methods and Results: The Danish AF Registry aims for complete registration and monitoring of care for all patients diagnosed with AF in Denmark. Administrative registries provide data on contacts to general practice, contacts to private cardiology practice, hospital contacts, medication prescriptions, updated vital status information, and biochemical test results. The Danish Stroke Registry provides information on stroke events. From 2017 to 2021, the proportion with a reported echocardiography among incident AF patients increased from 39.9% (95% CI: 39.3-40.6) to 82.6% (95% CI: 82.1-83.1). The initiation of oral anticoagulant therapy among patients with incident AF and a CHA2DS2-VASc score of ≥1 in men and ≥2 in women increased from 85.3% (95% CI: 84.6-85.9) to 90.4% (95% CI: 89.9-91.0). The 1-year and 2-year persistence increased from 85.2% (95% CI: 84.5-85.9) to 88.7% (95% CI: 88.0-89.3), and from 85.4% (95% CI: 84.7-86.2) to 88.2% (95% CI: 87.5-88.8), respectively. The 1-year risk of ischemic stroke among prevalent patients with AF decreased from 0.88% (95% CI: 0.83-0.93) to 0.71% (95% CI: 0.66-0.75). Variation in clinical performance between the five administrative Danish regions was reduced. Conclusion: Continuous nationwide monitoring of quality indicators for AF originating from administrative registries is feasible and supportive of improvements of quality of care.

Electrocardiographic Morphology-Voltage-P-Wave-Duration (MVP) Score to Select Patients for Continuous Atrial Fibrillation Screening to Prevent Stroke.

Morphology-voltage-P-wave-duration (MVP) score combining P-wave duration (PWD), P-wave voltage in lead I (PWVI), and interatrial block (IAB) has been demonstrated to predict atrial fibrillation (AF). Therefore, this study aimed to examine MVP score and its P-wave components as potential predictors of AF screening effects on stroke prevention. This was a secondary analysis of the LOOP Study (Atrial Fibrillation detected by Continuous ECG Monitoring using Implantable Loop Recorder to prevent Stroke in High-risk Individuals) which randomized older persons (aged 70 to 90 years) with additional stroke risk factors to either continuous monitoring with implantable loop recorder and anticoagulation upon detection of AF episodes ≥6 minutes (the intervention group), or usual care. A total of 5,759 participants were included in the present analysis, where PWD, PWVI, and IAB were determined through a computerized analysis of 12-lead electrocardiogram and further employed to calculate baseline MVP score (0 to 6) for each participant. In total, 305 (5.3%) had stroke or systemic embolism during follow-up, with a higher risk in the group with MVP score 5 to 6 than those having score 0 to 2 (hazard ratio (HR) 1.54 [95% confidence interval (CI) 1.01 to 2.35]). This risk increase was mainly upheld by participants with IAB (HR 1.62 [95% CI 1.11 to 2.36] for IAB vs no IAB) and with longer PWD (HR 1.37 [95% CI 1.07 to 1.75] for >110 vs ≤110 ms). Compared with usual care, implantable loop recorder screening did not significantly reduce the risk of stroke or systemic embolism in any MVP risk categories (HR 0.80 [95% CI 0.60 to 1.08] for MVP score 0 to 2, 0.54 [95% CI 0.16 to 1.85] for MVP score 3 to 4, and 0.89 [95% CI 0.35 to 2.25] for MVP score 5 to 6; pinteraction = 0.78). In conclusion, a higher MVP score was associated with an increased stroke risk, but it did not demonstrate an association with effects of AF screening on stroke prevention. These findings should be considered hypothesis-generating and warrant further study.

Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes.

BACKGROUND: Device-detected atrial high-rate episodes (AHREs) are atrial arrhythmias detected by implanted cardiac devices. AHREs resemble atrial fibrillation but are rare and brief. Whether the occurrence of AHREs in patients without atrial fibrillation (as documented on a conventional electrocardiogram [ECG]) justifies the initiation of anticoagulants is not known. METHODS: We conducted an event-driven, double-blind, double-dummy, randomized trial involving patients 65 years of age or older who had AHREs lasting for at least 6 minutes and who had at least one additional risk factor for stroke. Patients were randomly assigned in a 1:1 ratio to receive edoxaban or placebo. The primary efficacy outcome was a composite of cardiovascular death, stroke, or systemic embolism, evaluated in a time-to-event analysis. The safety outcome was a composite of death from any cause or major bleeding. RESULTS: The analysis population consisted of 2536 patients (1270 in the edoxaban group and 1266 in the placebo group). The mean age was 78 years, 37.4% were women, and the median duration of AHREs was 2.8 hours. The trial was terminated early, at a median follow-up of 21 months, on the basis of safety concerns and the results of an independent, informal assessment of futility for the efficacy of edoxaban; at termination, the planned enrollment had been completed. A primary efficacy outcome event occurred in 83 patients (3.2% per patient-year) in the edoxaban group and in 101 patients (4.0% per patient-year) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.60 to 1.08; P = 0.15). The incidence of stroke was approximately 1% per patient-year in both groups. A safety outcome event occurred in 149 patients (5.9% per patient-year) in the edoxaban group and in 114 patients (4.5% per patient-year) in the placebo group (hazard ratio, 1.31; 95% CI, 1.02 to 1.67; P = 0.03). ECG-diagnosed atrial fibrillation developed in 462 of 2536 patients (18.2% total, 8.7% per patient-year). CONCLUSIONS: Among patients with AHREs detected by implantable devices, anticoagulation with edoxaban did not significantly reduce the incidence of a composite of cardiovascular death, stroke, or systemic embolism as compared with placebo, but it led to a higher incidence of a composite of death or major bleeding. The incidence of stroke was low in both groups. (Funded by the German Center for Cardiovascular Research and others; NOAH-AFNET 6 ClinicalTrials.gov number, NCT02618577; ISRCTN number, ISRCTN17309850.).