BACKGROUND: Short and rare episodes of atrial fibrillation (AF) are commonly detected using implanted devices (device-detected AF) in patients with prior stroke or transient ischemic attack (TIA). The effectiveness and safety of oral anticoagulation in patients with prior stroke or TIA and device-detected AF but with no ECG-documented AF is unclear. METHODS AND RESULTS: This prespecified analysis of the NOAH-AFNET 6 (Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes) trial with post hoc elements assessed the effect of oral anticoagulation in patients with device-detected AF with and without a prior stroke or TIA in the randomized, double-blind, double-dummy NOAH-AFNET 6 trial. Outcomes were stroke, systemic embolism, and cardiovascular death (primary outcome) and major bleeding and death (safety outcome). A prior stroke or TIA was found in 253 patients with device-detected AF randomized in the NOAH-AFNET 6 (mean age, 78 years; 36.4% women). There was no treatment interaction with prior stroke or TIA for any of the primary and secondary time-to-event outcomes. In patients with a prior stroke or TIA, 14 out of 122 patients experienced a primary outcome event with anticoagulation (5.7% per patient-year). Without anticoagulation, there were 16 out of 131 patients with an event (6.3% per patient-year). The rate of stroke was lower than expected (anticoagulation: 4 out of 122 [1.6% per patient-year]; no anticoagulation: 6 out of 131 [2.3% per patient-year]). Numerically, there were more major bleeding events with anticoagulation in patients with prior stroke or TIA (8 out of 122 patients) than without anticoagulation (2 out of 131 patients). CONCLUSIONS: Anticoagulation appears to have ambiguous effects in patients with device-detected AF and a prior stroke or TIA in this hypothesis-generating analysis of the NOAH-AFNET 6 in the absence of ECG-documented AF, partially due to a low rate of stroke without anticoagulation.

• Klíčová slova
• CHA2DS2‐VASc score, NOAH‐AFNET 6, anticoagulation, atrial fibrillation, device‐detected atrial fibrillation, recurrent stroke,
• MeSH
• antikoagulancia * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• aplikace orální MeSH
• časové faktory MeSH
• cévní mozková příhoda * prevence a kontrola   etiologie   MeSH
• dvojitá slepá metoda MeSH
• fibrilace síní * farmakoterapie   komplikace   diagnóza   MeSH
• kardiostimulátor MeSH
• krvácení chemicky indukované   MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• tranzitorní ischemická ataka * prevence a kontrola   etiologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antikoagulancia * MeSH

A significant proportion of patients who suffer from atrial fibrillation (AF) and are in need of thromboembolic protection are not treated with oral anticoagulation or discontinue this treatment shortly after its initiation. This undertreatment has not improved sufficiently despite the availability of direct oral anticoagulants which are associated with less major bleeding than vitamin K antagonists. Multiple reasons account for this, including bleeding events or ischaemic strokes whilst on anticoagulation, a serious risk of bleeding events, poor treatment compliance despite best educational attempts, or aversion to drug therapy. An alternative interventional therapy, which is not associated with long-term bleeding and is as effective as vitamin K anticoagulation, was introduced over 20 years ago. Because of significant improvements in procedural safety over the years, left atrial appendage closure, predominantly achieved using a catheter-based, device implantation approach, is increasingly favoured for the prevention of thromboembolic events in patients who cannot achieve effective anticoagulation. This management strategy is well known to the interventional cardiologist/electrophysiologist but is not more widely appreciated within cardiology or internal medicine. This article introduces the devices and briefly explains the implantation technique. The indications and device follow-up are more comprehensively described. Almost all physicians who care for adult patients will have many with AF. This practical guide, written within guideline/guidance boundaries, is aimed at those non-implanting physicians who may need to refer patients for consideration of this new therapy, which is becoming increasingly popular.

• Klíčová slova
• Anticoagulation, Atrial fibrillation, Bleeding, Left atrial appendage closure, Left atrial appendage occlusion, Prevention, Stroke,
• MeSH
• antikoagulancia škodlivé účinky   MeSH
• cévní mozková příhoda * prevence a kontrola   komplikace   MeSH
• dospělí MeSH
• fibrilace síní * komplikace   diagnóza   chirurgie   MeSH
• konsensus MeSH
• krvácení chemicky indukované   prevence a kontrola   MeSH
• lékaři * MeSH
• lidé MeSH
• síňové ouško * chirurgie   MeSH
• tromboembolie * etiologie   prevence a kontrola   MeSH
• uzávěr ouška levé síně MeSH
• vitamin K MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antikoagulancia MeSH
• vitamin K MeSH

AIMS: Heart failure (HF) is a risk factor for major adverse events in atrial fibrillation (AF). Whether this risk persists on non-vitamin K antagonist oral anticoagulants (NOACs) and varies according to left ventricular ejection fraction (LVEF) is debated. METHODS AND RESULTS: We investigated the relation of HF in the ETNA-AF-Europe registry, a prospective, multicentre, observational study with an overall 4-year follow-up of edoxaban-treated AF patients. We report 2-year follow-up for ischaemic stroke/transient ischaemic attack (TIA)/systemic embolic events (SEE), major bleeding, and mortality. Of the 13 133 patients, 1854 (14.1%) had HF. Left ventricular ejection fraction was available for 82.4% of HF patients and was <40% in 671 (43.9%) and ≥40% in 857 (56.1%). Patients with HF were older, more often men, and had more comorbidities. Annualized event rates (AnERs) of any stroke/SEE were 0.86%/year and 0.67%/year in patients with and without HF. Compared with patients without HF, those with HF also had higher AnERs for major bleeding (1.73%/year vs. 0.86%/year) and all-cause death (8.30%/year vs. 3.17%/year). Multivariate Cox proportional models confirmed HF as a significant predictor of major bleeding [hazard ratio (HR) 1.65, 95% confidence interval (CI): 1.20-2.26] and all-cause death [HF with LVEF <40% (HR 2.42, 95% CI: 1.95-3.00) and HF with LVEF ≥40% (HR 1.80, 95% CI: 1.45-2.23)] but not of ischaemic stroke/TIA/SEE. CONCLUSION: Anticoagulated patients with HF at baseline featured higher rates of major bleeding and all-cause death, requiring optimized management and novel preventive strategies. NOAC treatment was similarly effective in reducing risk of ischaemic events in patients with or without concomitant HF.

• Klíčová slova
• Atrial fibrillation, Edoxaban, Heart failure, Left ventricular ejection fraction, Non-vitamin K antagonist oral anticoagulant, Registry,
• MeSH
• antikoagulancia škodlivé účinky   MeSH
• aplikace orální MeSH
• cévní mozková příhoda * diagnóza   epidemiologie   etiologie   MeSH
• embolie * MeSH
• fibrilace síní * komplikace   diagnóza   farmakoterapie   MeSH
• funkce levé komory srdeční MeSH
• ischemická cévní mozková příhoda * MeSH
• ischemie mozku * MeSH
• krvácení chemicky indukované   MeSH
• lidé MeSH
• prospektivní studie MeSH
• registrace MeSH
• srdeční selhání * diagnóza   epidemiologie   MeSH
• tepový objem fyziologie   MeSH
• tranzitorní ischemická ataka * diagnóza   epidemiologie   prevence a kontrola   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Názvy látek
• antikoagulancia MeSH

Benefit of thrombolytic therapy in patients with acute stroke, who are on anticoagulant treatment, is not well addressed. The aim of this study was to investigate whether apixaban can modify the thrombolytic efficacy of alteplase in vitro. Static and flow models and two variants of red blood cell (RBC) dominant clots, with and without apixaban, were used. Clots were prepared from the blood of healthy human donors and subsequently exposed to alteplase treatment. Apixaban and alteplase were used in clinically relevant concentrations. Clot lysis in the static model was determined both by clot weight and spectrophotometric determination of RBC release. Clot lysis in the flow model was determined by measuring recanalization time, clot length and spectrophotometric determination of RBC release. In the static model, clots without apixaban; compared to those with apixaban had alteplase-induced mass loss 54 ± 8% vs. 53 ± 8%, p = 1.00; RBC release 0.14 ± 0.04 vs. 0.12 ± 0.04, p = 0.14, respectively. Very similar results were obtained if plasma was used instead of physiological buffered saline as the incubation medium. In the flow model, clot lysis without apixaban; compared to those with apixaban was as follows: recanalization time 107 ± 46 min vs. 127 ± 31 min, p = 1.00; recanalization frequency 90 ± 22% vs. 90 ± 22%, p = 1.00; clot volume reduction 32 ± 15% vs. 34 ± 10%, p = 1.00; RBC release 0.029 ± 0.007 vs. 0.022 ± 0.007, p = 0.16, respectively. Apixaban had no positive effect on alteplase-induced thrombolysis in both the in vitro static and flow models. Our data support current clinical practice, such that thrombolysis is contraindicated in stroke treatment for patients who have been treated with anticoagulants.

• Klíčová slova
• alteplase, apixaban, clot, in vitro, stroke, thrombolysis,
• Publikační typ
• časopisecké články MeSH

IMPORTANCE: The reported associations of cerebral microbleeds with recurrent stroke and intracerebral hemorrhage have raised concerns regarding antithrombotic treatment in patients with a history of stroke and microbleeds on magnetic resonance imaging. OBJECTIVE: To characterize microbleeds in embolic strokes of undetermined source (ESUS) and report interactions between microbleeds and the effects of random assignment to anticoagulant vs antiplatelet therapy. DESIGN, SETTING, AND PARTICIPANTS: Subgroup analyses of the New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs Aspirin to Prevent Embolism in ESUS (NAVIGATE ESUS) international, double-blind, randomized, event-driven phase 3 clinical trial. Participants were enrolled between December 2014 and September 2017 and followed up for a median of 11 months. The study setting included 459 stroke recruitment centers in 31 countries. Patients aged 50 years or older who had neuroimaging-confirmed ESUS between 7 days and 6 months before screening were eligible. Of these 7213 NAVIGATE ESUS participants, 3699 (51%) had information on cerebral microbleeds reported on their baseline clinical magnetic resonance imaging and were eligible for these analyses. Patients with a prior history of symptomatic intracerebral hemorrhage were excluded from the NAVIGATE ESUS trial. INTERVENTIONS: Rivaroxaban, 15 mg, compared with aspirin, 100 mg, daily. MAIN OUTCOMES AND MEASURES: The primary outcome was recurrent stroke. Secondary outcomes were ischemic stroke, intracerebral hemorrhage, and all-cause mortality. RESULTS: Microbleeds were present in 395 of 3699 participants (11%). Of patients with cerebral microbleeds, mean (SD) age was 69.5 (9.4) years, 241 were men (61%), and 201 were White (51%). Advancing age (odds ratio [OR] per year, 1.03; 95% CI, 1.01-1.04), East Asian race/ethnicity (OR, 1.57; 95% CI, 1.04-2.37), hypertension (OR, 2.20; 95% CI, 1.54-3.15), multiterritorial infarcts (OR, 1.95; 95% CI, 1.42-2.67), chronic infarcts (OR, 1.78; 95% CI, 1.42-2.23), and occult intracerebral hemorrhage (OR, 5.23; 95% CI, 2.76-9.90) were independently associated with microbleeds. The presence of microbleeds was associated with a 1.5-fold increased risk of recurrent stroke (hazard ratio [HR], 1.5; 95% CI, 1.0-2.3), a 4-fold risk of intracerebral hemorrhage (HR, 4.2; 95% CI, 1.3-13.9), a 2-fold risk of all-cause mortality (HR, 2.1; 95% CI, 1.1-4.3), and strictly lobar microbleeds with an approximately 2.5-fold risk of ischemic stroke (HR, 2.3; 95% CI, 1.3-4.3). There were no interactions between microbleeds and treatment assignments for recurrent stroke, ischemic stroke, or all-cause mortality. The HR of intracerebral hemorrhage on rivaroxaban was similar between persons with microbleeds (HR, 3.1; 95% CI, 0.3-30.0) and persons without microbleeds (HR, 3.0; 95% CI, 0.6-14.7; interaction P = .97). CONCLUSIONS AND RELEVANCE: Microbleeds mark an increased risk of recurrent stroke, ischemic stroke, intracerebral hemorrhage, and mortality in ESUS but do not appear to influence effects of rivaroxaban on clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02313909.

• MeSH
• antikoagulancia terapeutické užití   MeSH
• Aspirin terapeutické užití   MeSH
• cerebrální krvácení epidemiologie   etiologie   MeSH
• dvojitá slepá metoda MeSH
• embolická cévní mozková příhoda komplikace   farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prevalence MeSH
• recidiva MeSH
• rivaroxaban terapeutické užití   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antikoagulancia MeSH
• Aspirin MeSH
• rivaroxaban MeSH

• Klíčová slova
• Ablation, Anticoagulation, Arrhythmia, Atrial fibrillation, Atrial flutter, Atrial tachycardia, Catheter ablation, Stroke, Surgical ablation,
• MeSH
• fibrilace síní diagnóza   patofyziologie   chirurgie   MeSH
• katetrizační ablace škodlivé účinky   normy   MeSH
• konsensus MeSH
• kryochirurgie škodlivé účinky   normy   MeSH
• lidé MeSH
• rizikové faktory MeSH
• srdeční katetrizace škodlivé účinky   normy   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• směrnice pro lékařskou praxi MeSH

• Klíčová slova
• Ablation, Anticoagulation, Arrhythmia, Atrial fibrillation, Atrial flutter, Atrial tachycardia, Catheter ablation, Stroke, Surgical ablation,
• MeSH
• ablace normy   MeSH
• fibrilace síní chirurgie   MeSH
• kardiologie * MeSH
• katetrizační ablace normy   MeSH
• konsensuální konference jako téma * MeSH
• lidé MeSH
• převodní systém srdeční chirurgie   MeSH
• společnosti lékařské * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• zprávy MeSH

BACKGROUND: Embolic strokes of undetermined source comprise up to 20% of ischemic strokes. The stroke recurrence rate is substantial with aspirin, widely used for secondary prevention. The New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus ASA to prevenT Embolism in Embolic Stroke of Undetermined Source international trial will compare the efficacy and safety of rivaroxaban, an oral factor Xa inhibitor, versus aspirin for secondary prevention in patients with recent embolic strokes of undetermined source. MAIN HYPOTHESIS: In patients with recent embolic strokes of undetermined source, rivaroxaban 15 mg once daily will reduce the risk of recurrent stroke (both ischemic and hemorrhagic) and systemic embolism (primary efficacy outcome) compared with aspirin 100 mg once daily. DESIGN: Double-blind, randomized trial in patients with embolic strokes of undetermined source, defined as nonlacunar cryptogenic ischemic stroke, enrolled between seven days and six months from the qualifying stroke. The planned sample size of 7000 participants will be recruited from approximately 480 sites in 31 countries between 2014 and 2017 and followed for a mean of about two years until at least 450 primary efficacy outcome events have occurred. The primary safety outcome is major bleeding. Two substudies assess (1) the relative effect of treatments on MRI-determined covert brain infarcts and (2) the biological underpinnings of embolic strokes of undetermined source using genomic and biomarker approaches. SUMMARY: The New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus ASA to prevenT Embolism in Embolic Stroke of Undetermined Source trial is evaluating the benefits and risks of rivaroxaban for secondary stroke prevention in embolic strokes of undetermined source patients. Main results are anticipated in 2018.

• Klíčová slova
• Stroke, aspirin, cerebral embolism, cryptogenic stroke, embolic stroke of undetermined source, randomized trial, rivaroxaban, stroke prevention,
• Publikační typ
• časopisecké články MeSH

• Klíčová slova
• apixaban, aspirin,
• Publikační typ
• úvodníky MeSH

AIMS: The risk of stroke in patients with atrial fibrillation (AF) increases with age. In the ARISTOTLE trial, apixaban when compared with warfarin reduced the rate of stroke, death, and bleeding. We evaluated these outcomes in relation to patient age. METHODS AND RESULTS: A total of 18 201 patients with AF and a raised risk of stroke were randomized to warfarin or apixaban 5 mg b.d. with dose reduction to 2.5 mg b.d. or placebo in 831 patients with ≥2 of the following criteria: age ≥80 years, body weight ≤60 kg, or creatinine ≥133 μmol/L. We used Cox models to compare outcomes in relation to patient age during 1.8 years median follow-up. Of the trial population, 30% were <65 years, 39% were 65 to <75, and 31% were ≥75 years. The rates of stroke, all-cause death, and major bleeding were higher in the older age groups (P < 0.001 for all). Apixaban was more effective than warfarin in preventing stroke and reducing mortality across all age groups, and associated with less major bleeding, less total bleeding, and less intracranial haemorrhage regardless of age (P interaction >0.11 for all). Results were also consistent for the 13% of patients ≥80 years. No significant interaction with apixaban dose was found with respect to treatment effect on major outcomes. CONCLUSION: The benefits of apixaban vs. warfarin were consistent in patients with AF regardless of age. Owing to the higher risk at older age, the absolute benefits of apixaban were greater in the elderly.

• Klíčová slova
• Age, Anticoagulants, Apixaban, Atrial fibrillation, Bleeding, Stroke,
• MeSH
• analýza rozptylu MeSH
• antikoagulancia aplikace a dávkování   škodlivé účinky   MeSH
• cévní mozková příhoda mortalita   prevence a kontrola   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• embolie mortalita   prevence a kontrola   MeSH
• fibrilace síní farmakoterapie   mortalita   MeSH
• inhibitory faktoru Xa aplikace a dávkování   škodlivé účinky   MeSH
• Kaplanův-Meierův odhad MeSH
• krvácení chemicky indukované   mortalita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• pyrazoly aplikace a dávkování   škodlivé účinky   MeSH
• pyridony aplikace a dávkování   škodlivé účinky   MeSH
• rizikové faktory MeSH
• rozvrh dávkování léků MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• věkové faktory MeSH
• výsledek terapie MeSH
• warfarin aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• antikoagulancia MeSH
• apixaban MeSH Prohlížeč
• inhibitory faktoru Xa MeSH
• pyrazoly MeSH
• pyridony MeSH
• warfarin MeSH