Stroke Prevention by Anticoagulants in Daily Practice Depending on Atrial Fibrillation Pattern and Clinical Risk Factors.

Background and Purpose: The objective of the study was to assess the effectiveness of individual direct oral anticoagulants versus vitamin K antagonists for primary prevention of stroke (ischemic and hemorrhagic) in routine clinical practice in patients with various clinical risk factors depending on their atrial fibrillation (AF) patterns. Methods: A nested case-referent study was conducted using data from 2 national registries of patients with stroke and AF. Stroke cases with previous history of AF were matched to up to 2 randomly selected referent patients with AF and no stroke. The association of individual anticoagulant use with ischemic or hemorrhagic stroke was studied in patients with or without permanent AF using multivariable conditional logistic models, controlled for clinically significant risk factors and multiple other cardiovascular risk factors. Results: In total, 2586 stroke cases with previous AF and 4810 nonstroke referent patients with AF were retained for the study. Direct oral anticoagulant users had lower odds of stroke of any type than vitamin K antagonist users: the adjusted-matched OR for ischemic stroke were 0.70 (95% CI, 0.50­0.98) for dabigatran, 0.68 (95% CI, 0.53­0.86) for rivaroxaban, and 0.73 (95% CI, 0.52­1.02) for apixaban while for hemorrhagic stroke they were 0.31 (95% CI, 0.14­0.68), 0.64 (95% CI, 0.39­1.06), and 0.70 (95% CI, 0.33­1.49), respectively. The effects of individual direct oral anticoagulants relative to vitamin K antagonists were similar in permanent AF and nonpermanent AF patients. Conclusions: Similar results were observed for each direct oral anticoagulant in real life as those observed in the pivotal clinical trials. The pattern of AF did not affect the outcome.

The association between patterns of atrial fibrillation, anticoagulation, and cardiovascular events.

AIMS: Guidelines do not recommend to take pattern of atrial fibrillation (AF) into account for the indication of anticoagulation (AC). We assessed AF pattern and the risk of cardiovascular events during 2-years of follow-up. METHODS AND RESULTS: We categorized AF as paroxysmal, persistent, or permanent in 29 181 patients enrolled (2010-15) in the Global Anticoagulant Registry In the FIELD of AF (GARFIELD-AF). We used multivariable Cox regression to assess the risks of stroke/systemic embolism (SE) and death across patterns of AF, and whether this changed with AC on outcomes. Atrial fibrillation pattern was paroxysmal in 14 344 (49.2%), persistent in 8064 (27.6%), and permanent 6773 (23.2%) patients. Median CHA2DS2-VASc, GARFIELD-AF, and HAS-BLED scores assessing the risk of stroke/SE and/or bleeding were similar across AF patterns, but the risk of death, as assessed by the GARFIELD-AF risk calculator, was higher in non-paroxysmal than in paroxysmal AF patterns. During 2-year follow-up, after adjustment, non-paroxysmal AF patterns were associated with significantly higher rates of all-cause death, stroke/SE, and new/worsening congestive heart failure (CHF) than paroxysmal AF in non-anticoagulated patients only. In anticoagulated patients, a significantly higher risk of death but not of stroke/SE and new/worsening CHF persisted in non-paroxysmal compared with paroxysmal AF patterns. CONCLUSION: In non-anticoagulated patients, non-paroxysmal AF patterns were associated with higher risks of stroke/SE, new/worsening HF and death than paroxysmal AF. In anticoagulated patients, the risk of stroke/SE and new/worsening HF was similar across all AF patterns. Thus AF pattern is no longer prognostic for stroke/SE when patients are treated with anticoagulants. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362.

Determinants of left atrium thrombi in scheduled cardioversion: an ENSURE-AF study analysis.

AIMS: ENSURE-AF (NCT02072434) was the largest prospective randomized clinical trial of anticoagulation for cardioversion in atrial fibrillation (AF), which also provides the largest prospective dataset for transoesophageal echocardiography (TOE) prior to cardioversion. This ancillary analysis investigated determinants of TOE-detected left atrium thrombi (LAT) in patients scheduled for electrical cardioversion (ECV). METHODS AND RESULTS: The ENSURE-AF multicentre PROBE evaluation trial compared edoxaban 60 mg once daily (QD) with enoxaparin/warfarin in 2199 subjects undergoing ECV of non-valvular AF. Patients were stratified by the use of TOE, anticoagulant experience, and selected edoxaban dose. Electrical cardioversion was cancelled or deferred when TOEdetected LAT. In total, 1183 subjects were stratified to the TOE arm and LAT was reported in 91 (8.2%). In univariate analysis, age ≥75 years (26.4% vs. 16.9%, P = 0.0308), lower weight (86.5 ± 15.0 vs. 90.7 ± 18.0 kg, P = 0.0309), lower creatinine clearance (80.1 ± 30.6 vs. 93.2 ± 33.9 mL/min, P = 0.0007), heart failure (59.3% vs. 43.0%, P = 0.0029), and diuretic treatment (53.9% vs. 40.1%, P = 0.0141) were more prevalent in the LAT group. Non-significant trends were seen for higher mean CHA2DS2-VASc score (3.0 ± 1.41 vs. 2.7 ± 1.48, P = 0.0571) and more prevalent anticoagulation use prior to enrolment (60.4% vs. 50.3%, P = 0.0795) in the LAT group. In logistic regression analysis, age (P = 0.0202) and heart failure (P = 0.0064) were independently associated with LAT. CONCLUSION: Elective ECV is commonly cancelled or deferred due to TOE-detected LAT in patients with non-valvular AF. Age ≥75 years and heart failure were associated with the presence of LAT.

International longitudinal registry of patients with atrial fibrillation and treated with rivaroxaban: RIVaroxaban Evaluation in Real life setting (RIVER).

BACKGROUND: Real-world data on non-vitamin K oral anticoagulants (NOACs) are essential in determining whether evidence from randomised controlled clinical trials translate into meaningful clinical benefits for patients in everyday practice. RIVER (RIVaroxaban Evaluation in Real life setting) is an ongoing international, prospective registry of patients with newly diagnosed non-valvular atrial fibrillation (NVAF) and at least one investigator-determined risk factor for stroke who received rivaroxaban as an initial treatment for the prevention of thromboembolic stroke. The aim of this paper is to describe the design of the RIVER registry and baseline characteristics of patients with newly diagnosed NVAF who received rivaroxaban as an initial treatment. METHODS AND RESULTS: Between January 2014 and June 2017, RIVER investigators recruited 5072 patients at 309 centres in 17 countries. The aim was to enroll consecutive patients at sites where rivaroxaban was already routinely prescribed for stroke prevention. Each patient is being followed up prospectively for a minimum of 2-years. The registry will capture data on the rate and nature of all thromboembolic events (stroke / systemic embolism), bleeding complications, all-cause mortality and other major cardiovascular events as they occur. Data quality is assured through a combination of remote electronic monitoring and onsite monitoring (including source data verification in 10% of cases). Patients were mostly enrolled by cardiologists (n = 3776, 74.6%), by internal medicine specialists 14.2% (n = 718) and by primary care/general practice physicians 8.2% (n = 417). The mean (SD) age of the population was 69.5 (11.0) years, 44.3% were women. Mean (SD) CHADS2 score was 1.9 (1.2) and CHA2DS2-VASc scores was 3.2 (1.6). Almost all patients (98.5%) were prescribed with once daily dose of rivaroxaban, most commonly 20 mg (76.5%) and 15 mg (20.0%) as their initial treatment; 17.9% of patients received concomitant antiplatelet therapy. Most patients enrolled in RIVER met the recommended threshold for AC therapy (86.6% for 2012 ESC Guidelines, and 79.8% of patients according to 2016 ESC Guidelines). CONCLUSIONS: The RIVER prospective registry will expand our knowledge of how rivaroxaban is prescribed in everyday practice and whether evidence from clinical trials can be translated to the broader cross-section of patients in the real world. TRIAL REGISTRATION: Unique identifier: NCT02444221. Registerd 14 May 2015; Retrospectively Registered.

The influence of progression of atrial fibrillation on quality of life: a report from the Euro Heart Survey.

Aims: Progression of atrial fibrillation (AF) from paroxysmal to persistent forms is an active field of research. The influence of AF progression on health related quality of life (HRQoL) is currently unknown. We aimed to assess the influence of AF progression on HRQoL, and whether this association is mediated through symptoms, treatment, and major adverse events. Methods and results: In the Euro Heart Survey, 967 patients were included with paroxysmal AF who filled out EuroQoL-5D at baseline and at 1 year follow-up. Those who progressed (n = 132, 13.6%) developed more problems during follow-up than those who did not, on all EuroQoL-5D domains (increase in problems on mobility 20.5% vs. 11.4%; self-care 12.9% vs. 6.2%; usual activities 23.5% vs. 14.0%; pain/discomfort 20.5% vs. 13.7%; and anxiety/depression 22.7% vs. 15.7%; all P < 0.05), leading to a decrease in utility [baseline 0.744 ± 0.26, follow-up 0.674 ± 0.36; difference -0.07 (95% CI [-0.126,-0.013], P = 0.02)]. Multivariate analysis showed that the effect of progression on utility is mediated by a large effect of adverse events [stroke (-0.27 (95% CI [-0.43,-0.11]); P = 0.001], heart failure [-0.12 (95% CI [-0.20,-0.05]); P = 0.001], malignancy (-0.31 (95% CI [-0.56,-0.05]); P = 0.02] or implantation of an implantable cardiac defibrillator [-0.12 (95% CI [-0.23,-0.02]); P = 0.03)], as well as symptomatic AF [-0.04 (95% CI [-0.08,-0.01]); P = 0.008]. Conclusion: AF progression is associated with a decrease in HRQoL. However, multivariate analysis revealed that AF progression itself does not have a negative effect on HRQoL, but that this effect can be attributed to a minor effect of the associated symptoms and a major effect of associated adverse events.

Population movement and sudden cardiac arrest location.

BACKGROUND: Although the benefits of automatic external defibrillators are undeniable, their effectiveness could be dramatically improved. One of the key issues is the disparity between the locations of automatic external defibrillators and sudden cardiac arrests (SCAs). METHODS AND RESULTS: From emergency medical services and other Parisian agencies, data on all SCAs occurring in public places in Paris, France, were prospectively collected between 2000 and 2010 and recorded using 2020 grid areas. For each area, population density, population movements, and landmarks were analyzed. Of the 4176 SCAs, 1255 (30%) occurred in public areas, with a highly clustered distribution of SCAs, especially in areas containing major train stations (12% of SCAs in 0.75% of the Paris area). The association with population density was poor, with a nonsignificant increase in SCAs with population density (P=0.4). Occurrence of public SCAs was, in contrast, highly associated with population movements (P<0.001). In multivariate analysis including other landmarks in each grid cell in the model and demographic characteristics, population movement remained significantly associated with the occurrence of SCA (odds ratio, 1.48; 95% confidence interval, 1.34-1.63; P<0.0001), as well as grid cells containing train stations (odds ratio, 3.80; 95% confidence interval, 2.66-5.36; P<0.0001). CONCLUSIONS: Using a systematic analysis of determinants of SCA in public places, we demonstrated the extent to which population movements influence SCA distribution. Our findings also suggested that beyond this key risk factor, some areas are dramatically associated with a higher risk of SCA.

Causes-of-death analysis of patients with cardiac resynchronization therapy: an analysis of the CeRtiTuDe cohort study.

AIMS: The choice of resynchronization therapy between with (CRT-D) and without (CRT-P) a defibrillator remains a contentious issue. Cause-of-death analysis among CRT-P, compared with CRT-D, patients could help evaluate the extent to which CRT-P patients would have additionally benefited from a defibrillator in a daily clinical practice. METHODS AND RESULTS: A total of 1705 consecutive patients implanted with a CRT (CRT-P: 535 and CRT-D: 1170) between 2008 and 2010 were enrolled in CeRtiTuDe, a multicentric prospective follow-up cohort study, with specific adjudication for causes of death at 2 years. Patients with CRT-P compared with CRT-D were older (P < 0.0001), less often male (P < 0.0001), more symptomatic (P = 0.0005), with less coronary artery disease (P = 0.003), wider QRS (P = 0.002), more atrial fibrillation (P < 0.0001), and more co-morbidities (P = 0.04). At 2-year follow-up, the annual overall mortality rate was 83.80 [95% confidence interval (CI) 73.41-94.19] per 1000 person-years. The crude mortality rate among CRT-P patients was double compared with CRT-D (relative risk 2.01, 95% CI 1.56-2.58). In a Cox proportional hazards regression analysis, CRT-P remained associated with increased mortality (hazard ratio 1.54, 95% CI 1.07-2.21, P = 0.0209), although other potential confounders may persist. By cause-of-death analysis, 95% of the excess mortality among CRT-P subjects was related to an increase in non-sudden death. CONCLUSION: When compared with CRT-D patients, excess mortality in CRT-P recipients was mainly due to non-sudden death. Our findings suggest that CRT-P patients, as currently selected in routine clinical practice, would not potentially benefit with the addition of a defibrillator.

Survival from sports-related sudden cardiac arrest: In sports facilities versus outside of sports facilities.

BACKGROUND: We sought to evaluate frequency, characteristics, and outcomes of sudden cardiac arrest (SCA) during sports activities according to the location of occurrence (in sports facilities vs those occurring outside of sports facilities). METHODS AND RESULTS: This is an observational 5-year prospective national French survey of subjects 10 to 75 years old presenting with SCA during sports (2005-2010), in 60 French administrative regions (covering a population of 35 million people). Of the 820 SCA during sports, 426 SCAs (52%) occurred in sports facilities. Overall, a substantially higher survival rate at hospital discharge was observed among SCA in sports facilities (22.8%, 95% CI 18.8-26.8) compared to those occurring outside (8.0%, 95% CI 5.3-10.7) (P < .0001). Patients with SCA in sports facilities were younger (42.1 vs 51.3 years, P < .0001) and less frequently had known cardiovascular diseases (P < .0001). The events were more often witnessed (99.8% vs 84.9%, 0.0001), and bystander cardiopulmonary resuscitation was more frequently initiated (35.4% vs 25.9%, P = .003). Delays of intervention were significantly shorter when SCA occurred in sports facilities (9.3 vs 13.6, P=0.03), and the proportion of initially shockable rhythm was higher (58.8% vs 33.1%, P < .0001). Better survival in sports facilities was mainly explained by concomitant circumstances of occurrence (adjusted odds ratio 1.48, 95% CI 0.88-2.49, P = .134). CONCLUSIONS: Sports-related SCA is not a homogeneous entity. The 3-fold higher survival rate reported among sports-related SCA is mainly due to cases that occur in sports facilities, whereas SCA during sports occurring outside of sports facilities has the usual very low rate of survival.

Narrow therapeutic index drugs: a clinical pharmacological consideration to flecainide.

PURPOSE: The therapeutic index (TI) is the range of doses at which a medication is effective without unacceptable adverse events. Drugs with a narrow TI (NTIDs) have a narrow window between their effective doses and those at which they produce adverse toxic effects. Generic drugs may be substituted for brand-name drugs provided that they meet the recommended bioequivalence (BE) limits. However, an appropriate range of BE for NTIDs is essential to define due to the potential for ineffectiveness or adverse events. Flecainide is an antiarrhythmic agent that has the potential to be considered an NTID. This review aims to evaluate the literature surrounding guidelines on generic substitution for NTIDs and to evaluate the evidence for flecainide to be considered an NTID. METHODS: A review of recommendations from various regulatory authorities regarding BE and NTIDs, and publications regarding the NTID characteristics of flecainide, was carried out. RESULTS: Regulatory authorities generally recommend reduced BE limits for NTIDs. Some, but not all, regulatory authorities specify flecainide as an NTID. The literature review demonstrated that flecainide displays NTID characteristics including a steep drug dose-response relationship for safety and efficacy, a need for therapeutic drug monitoring of pharmacokinetic (PK) or pharmacodynamics measures and intra-subject variability in its PK properties. CONCLUSIONS: There is much evidence for flecainide to be considered an NTID based on both preclinical and clinical data. A clear understanding of the potential of proarrhythmic effects or lack of efficacy, careful patient selection and regular monitoring are essential for the safe and rational administration of flecainide.

Incidence of sudden cardiac death after ventricular fibrillation complicating acute myocardial infarction: a 5-year cause-of-death analysis of the FAST-MI 2005 registry.

AIMS: Limited data are available on long-term prognosis or causes-of-death analysis among survivors of acute myocardial infarction (MI) according to whether or not they developed ventricular fibrillation (VF) during the acute stage of MI. METHODS AND RESULTS: Among 3670 MI patients hospitalized in France in 2005 and enrolled in this prospective follow-up cohort study, we assessed in-hospital mortality and 5-year cause of death among those who survived to hospital discharge, according to whether they developed VF (116 cases) or not, during the acute stage. 94.5% of patients had complete follow-up at 5 years. In-hospital mortality was significantly higher among VF patients (adjusted OR 7.38, 95% CI 4.27-12.75, P < 0.001). Among 3463 survivors at hospital discharge, 1024 died during a mean follow-up of 52 ± 2 months. The overall survival rate at 5 years was 74.4% (95% CI 72.8-76.0). In Cox multivariate analysis, occurrence of VF during the acute phase of MI was not associated with an increased mortality at 5 years (HR 0.78, 95% CI 0.38-1.58, P = 0.21). The distribution of causes of death at 5 years did not statistically differ according to the presence or absence of VF, especially for sudden cardiac death (13.1% in VF group vs.12.9% in non-VF group), despite a very low rate of implantation of cardioverter defibrillator in both groups (Overall rate 1.2%). CONCLUSION: Patients developing VF in the setting of acute MI are at higher risk of in-hospital mortality. However, VF is not associated with a higher long-term all-cause or sudden cardiac death mortality.

Rivaroxaban vs. vitamin K antagonists for cardioversion in atrial fibrillation.

AIMS: X-VeRT is the first prospective randomized trial of a novel oral anticoagulant in patients with atrial fibrillation undergoing elective cardioversion. METHODS AND RESULTS: We assigned 1504 patients to rivaroxaban (20 mg once daily, 15 mg if creatinine clearance was between 30 and 49 mL/min) or dose-adjusted vitamin K antagonists (VKAs) in a 2:1 ratio. Investigators selected either an early (target period of 1-5 days after randomization) or delayed (3-8 weeks) cardioversion strategy. The primary efficacy outcome was the composite of stroke, transient ischaemic attack, peripheral embolism, myocardial infarction, and cardiovascular death. The primary safety outcome was major bleeding. The primary efficacy outcome occurred in 5 (two strokes) of 978 patients (0.51%) in the rivaroxaban group and in 5 (two strokes) of 492 patients (1.02%) in the VKA group [risk ratio 0.50; 95% confidence interval (CI) 0.15-1.73]. In the rivaroxaban group, four patients experienced primary efficacy events following early cardioversion (0.71%) and one following delayed cardioversion (0.24%). In the VKA group, three patients had primary efficacy events following early cardioversion (1.08%) and two following delayed cardioversion (0.93%). Rivaroxaban was associated with a significantly shorter time to cardioversion compared with VKAs (P < 0.001). Major bleeding occurred in six patients (0.6%) in the rivaroxaban group and four patients (0.8%) in the VKA group (risk ratio 0.76; 95% CI 0.21-2.67). CONCLUSION: Oral rivaroxaban appears to be an effective and safe alternative to VKAs and may allow prompt cardioversion. NAME OF THE TRIAL REGISTRY: Clinicaltrials.gov; TRIAL REGISTRATION NUMBER: NCT01674647.

Causes of death and influencing factors in patients with atrial fibrillation: a competing-risk analysis from the randomized evaluation of long-term anticoagulant therapy study.

BACKGROUND: Atrial fibrillation is associated with increased mortality, but the specific causes of death and their predictors have not been described among patients on effective anticoagulant therapy. METHODS AND RESULTS: The Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial randomized 18 113 patients (age, 71.5 ± 9 years; male, 64%; CHADS2 score, 2.1 ± 1) to receive dabigatran or warfarin. Median follow-up was 2 years, and complete follow-up was achieved in 99.9% of patients. All deaths were categorized by the investigators using prespecified definitions followed by central adjudication. Overall, 1371 deaths occurred (annual mortality rate, 3.84%; 95% confidence interval [CI], 3.64-4.05). Cardiac deaths (sudden cardiac death and progressive heart failure) accounted for 37.4% of all deaths, whereas stroke- and hemorrhage-related deaths represented 9.8% of the total mortality. An examination of the causes of death according to dabigatran or warfarin showed that dabigatran significantly reduced vascular (embolism and hemorrhage-related) mortality (relative risk, 0.63; 95% CI, 0.45-0.88; P=0.007), whereas other causes of death were similar between treatments, including cardiac mortality (relative risk, 0.96; 95% CI, 0.80-1.15; P=0.638). The two strongest independent predictors of cardiac death in this population were heart failure (hazard ratio, 3.02; 95% CI, 2.45-3.73; P<0.0001), and prior myocardial infarction (hazard ratio, 2.05; 95% CI, 1.61-2.62; P<0.0001). CONCLUSIONS: The majority of deaths are not related to stroke in a contemporary anticoagulated atrial fibrillation population. These results emphasize the need to identify interventions beyond effective anticoagulation to further reduce mortality in atrial fibrillation. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.

The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study.

BACKGROUND: During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. METHODS AND RESULTS: Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow-up, 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomly assigned to receive dabigatran in RE-LY and 86% of RELY-ABLE-eligible patients. Rates of stroke or systemic embolism were 1.46% and 1.60%/y on dabigatran 150 and 110 mg twice daily, respectively (hazard ratio, 0.91; 95% confidence interval, 0.69-1.20). Rates of major hemorrhage were 3.74% and 2.99%/y on dabigatran 150 and 110 mg (hazard ratio, 1.26; 95% confidence interval, 1.04-1.53). Rates of death were 3.02% and 3.10%/y (hazard ratio, 0.97; 95% confidence interval, 0.80-1.19). Rates of hemorrhagic stroke were 0.13% and 0.14%/y. CONCLUSIONS: During 2.3 years of continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily in comparison with 110 mg, and similar rates of stroke and death.

Rationale and design of the eXplore the efficacy and safety of once-daily oral riVaroxaban for the prEvention of caRdiovascular events in patients with nonvalvular aTrial fibrillation scheduled for cardioversion trial: A comparison of oral rivaroxaban once daily with dose-adjusted vitamin K antagonists in patients with nonvalvular atrial fibrillation undergoing elective cardioversion.

BACKGROUND: Anticoagulation before, during, and after cardioversion is effective in reducing stroke risk in patients with atrial fibrillation. OBJECTIVE: The objective of this study is to explore the efficacy and safety of rivaroxaban 20 mg once daily (15 mg if creatinine clearance is 30-49 mL/min) compared with dose-adjusted vitamin K antagonists (VKAs; international normalized ratio 2.0-3.0) in patients scheduled for elective cardioversion. METHODS: This is a prospective, randomized, open-label, parallel group comparison of approximately 1,500 patients from 17 countries with hemodynamically stable nonvalvular atrial fibrillation of >48 hours or unknown duration. Patients will be randomized 2:1 (rivaroxaban:VKA) using 2 cardioversion strategies: the first approach is early cardioversion with the precardioversion anticoagulation goal of 1 to 5 days using rivaroxaban or usual therapy (heparin + VKA). In these patients, transesophageal echocardiography will be encouraged to exclude atrial thrombi. The alternative approach is delayed cardioversion. Rivaroxaban or VKA will be administered for 21 to 56 days before cardioversion. All patients will receive study treatment for 6 weeks postcardioversion. The primary efficacy end point is a composite of all strokes, transient ischemic attacks, noncentral nervous system systemic emboli, myocardial infarctions, and cardiovascular deaths. Each primary end point component will be evaluated separately, and additional composites will be investigated. The principal safety end point is major bleeding. CLINICAL CONTEXT: This will be the first prospective study of a novel oral anticoagulant in the setting of cardioversion. It will provide important information regarding the use of rivaroxaban in the periods preceding and after cardioversion in a broad patient population.

Management of atrial fibrillation in seven European countries after the publication of the 2010 ESC Guidelines on atrial fibrillation: primary results of the PREvention oF thromboemolic events--European Registry in Atrial Fibrillation (PREFER in AF).

AIMS: We sought to describe the management of patients with atrial fibrillation (AF) in Europe after the release of the 2010 AF Guidelines of the European Society of Cardiology. METHODS AND RESULTS: The PREFER in AF registry enrolled consecutive patients with AF from January 2012 to January 2013 in 461 centres in seven European countries. Seven thousand two hundred and forty-three evaluable patients were enrolled, aged 71.5 ± 11 years, 60.1% male, CHA2DS2VASc score 3.4 ± 1.8 (mean ± standard deviation). Thirty per cent patients had paroxysmal, 24.0% had persistent, 7.2% had long-standing persistent, and 38.8% had permanent AF. Oral anticoagulation was used in the majority of patients: 4799 patients (66.3%) received a vitamin K antagonist (VKA) as mono-therapy, 720 patients a combination of VKA and antiplatelet agents (9.9%), 442 patients (6.1%) a new oral anticoagulant drugs (NOAC). Antiplatelet agents alone were given to 808 patients (11.2%), no antithrombotic therapy to 474 patients (6.5%). Of 7034 evaluable patients, 5530 (78.6%) patients were adequately rate controlled (mean heart rate 60-100 bpm). Half of the patients (50.7%) received rhythm control therapy by electrical cardioversion (18.1%), pharmacological cardioversion (19.5%), antiarrhythmic drugs (amiodarone 24.1%, flecainide or propafenone 13.5%, sotalol 5.5%, dronedarone 4.0%), and catheter ablation (5.0%). CONCLUSION: The management of AF patients in 2012 has adapted to recent evidence and guideline recommendations. Oral anticoagulant therapy with VKA (majority) or NOACs is given to over 80% of eligible patients, including those at risk for bleeding. Rate is often adequately controlled, and rhythm control therapy is widely used.

Major regional disparities in outcomes after sudden cardiac arrest during sports.

AIMS: Characteristics of sudden cardiac arrest (SCA) during sports offers a novel (and unexplored) setting to assess factors associated with disparities in outcomes across regions. METHODS AND RESULTS: From a prospective 5-year community-based French registry concerning SCA during sports in 10-75 year-olds, we evaluated whether outcomes differed significantly between geographic regions. We then determined the extent to which variations in community-related early interventions were associated with regional variations in survival. Among 820 SCA cases studied, overall survival at hospital discharge was 15.7% (95% confidence interval, 13.2-18.2%), with considerable regional disparities (from 3.4 to 42.6%, P < 0.001). Major differences were noted regarding bystander initiation of cardiopulmonary resuscitation (15.3-80.9%, P < 0.001) and presence of initial shockable rhythm (28.6-79.1%, P < 0.001), with higher values of these being associated with better survival rates. The proportion of survivors with favourable neurological outcome at discharge was fairly uniform among survival groups (CPC-1/2, varying from 77.4 to 90.0%, P = 0.83). No difference was observed regarding subjects' characteristics and circumstances of SCA occurrence, including delays in resuscitation (collapse-to-call period). With a comparable in-hospital mortality (P = 0.44), survival at hospital discharge was highly correlated with that at hospital admission (regional variations from 7.4 to 75.0%, P < 0.001). CONCLUSION: Major regional disparities exist in survival rates (up to 10-fold) after SCA during sports. SCA cases from regions with the highest levels of bystander resuscitation had the best survival rates to hospital admission and discharge.

Sports-related sudden death in the general population.

BACKGROUND: Although such data are available for young competitive athletes, the prevalence, characteristics, and outcome of sports-related sudden death have not been assessed previously in the general population. METHODS AND RESULTS: A prospective and comprehensive national survey was performed throughout France from 2005 to 2010, involving subjects 10 to 75 years of age. Case detection for sports-related sudden death, including resuscitated cardiac arrest, was undertaken via national ambulance service reporting and Web-based screening of media releases. The overall burden of sports-related sudden death was 4.6 cases per million population per year, with 6% of cases occurring in young competitive athletes. Sensitivity analyses used to address suspected underreporting demonstrated an incidence ranging from 5 to 17 new cases per million population per year. More than 90% of cases occurred in the context of recreational sports. The age of subjects was relatively young (mean ± SD 46 ± 15 years), with a predominance of men (95%). Although most cases were witnessed (93%), bystander cardiopulmonary resuscitation was only commenced in 30.7% of cases. Bystander cardiopulmonary resuscitation (odds ratio 3.73, 95% confidence interval 2.19 to 6.39, P<0.0001) and initial use of cardiac defibrillation (odds ratio 3.71, 95% confidence interval 2.07 to 6.64, P<0.0001) were the strongest independent predictors for survival to hospital discharge (15.7%, 95% confidence interval 13.2% to 18.2%). CONCLUSIONS: Sports-related sudden death in the general population is considerably more common than previously suspected. Most cases are witnessed, yet bystander cardiopulmonary resuscitation was only initiated in one third of cases. Given the often predictable setting of sports-related sudden death and that prompt interventions were significantly associated with improved survival, these data have implications for health services planning.

Progression of atrial fibrillation in the REgistry on Cardiac rhythm disORDers assessing the control of Atrial Fibrillation cohort: clinical correlates and the effect of rhythm-control therapy.

INTRODUCTION: Paroxysmal atrial fibrillation (AF) may progress to persistent AF. We studied the clinical correlates and the effect of rhythm-control strategy on AF progression. METHODS: RecordAF was a worldwide prospective survey of AF management. Consecutive eligible patients with recent-onset AF were included and allocated to rate or rhythm control according to patient/physician choice. A total of 2,137 patients were followed up for 12 months. Atrial fibrillation progression was defined as a change from paroxysmal to persistent/permanent AF. RESULTS: Progression of AF occurred in 318 patients (15%) after 1 year. Patients with AF progression were older; had a higher diastolic blood pressure; and more often had a history of coronary artery disease, stroke or transient ischemic attack, hypertension, or heart failure. Patients treated with rhythm control were less likely to show progression than those treated only with rate control (164/1542 [11%] vs 154/595 [26%], P < .001). Multivariable analysis showed that history of heart failure (odds ratio [OR] 2.2, 95% CI 1.7-2.9, P < .0001), history of hypertension (OR 1.5, 95% CI 1.1-2.0, P = .01), and rate control rather than rhythm control (OR 3.2, 95% CI 2.5-4.1, P < .0001) were independent predictors of AF progression. The propensity score-adjusted OR of AF progression in patients with rate rather than rhythm control was 3.3 (95% CI 2.4-4.6, P < .0001). CONCLUSIONS: Although heart failure and hypertension are associated with AF progression, rhythm control is associated with lower risk of AF progression.

Management of ventricular and atrial arrhythmias in humans: towards a patient-specific approach.

The strategy of sudden cardiac death prevention by implantable cardioverter defibrillator, in primary prevention, is mainly based on the value of ejection fraction. That means that the approach is not really patient specific. A lot of implanted patients will not receive any shock. The implantation of large categories of patients is interesting on a global therapeutical point of view but, when considering the economical aspects, it would be more useful to have better selection criteria in order to obtain a more patient-specific approach, avoiding implanting patients who will never receive shocks. The parameters commonly used to select patients for implantations have a good negative predictive value but a low positive predictive value. Concerning atrial fibrillation the approach is quite different. Antiarrhythmic drug treatment has shown many limitations. Antiarrhythmic drugs are useful and safe in atrial fibrillation patients only if the contra-indications are strictly respected. The main difficulty concerns patients with both heart failure and atrial fibrillation. The story of Dronedarone development is illustrative of the necessity of a patient-specific approach in the treatment strategy of atrial fibrillation. The ATHENA trial made with Dronedarone showed a benefit in patients with underlying heart disease but no patient with advanced cardiopathy was included in the study. On the contrary, the PALLAS trial has clearly shown that the drug is contra-indicated in patients with any type of heart failure. In atrial fibrillation, a patient-specific approach is mandatory. This review illustrates the dichotomy of the two different approaches.