EHRA expert consensus document on the management of arrhythmias in frailty syndrome, endorsed by the Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA).

There is an increasing proportion of the general population surviving to old age with significant chronic disease, multi-morbidity, and disability. The prevalence of pre-frail state and frailty syndrome increases exponentially with advancing age and is associated with greater morbidity, disability, hospitalization, institutionalization, mortality, and health care resource use. Frailty represents a global problem, making early identification, evaluation, and treatment to prevent the cascade of events leading from functional decline to disability and death, one of the challenges of geriatric and general medicine. Cardiac arrhythmias are common in advancing age, chronic illness, and frailty and include a broad spectrum of rhythm and conduction abnormalities. However, no systematic studies or recommendations on the management of arrhythmias are available specifically for the elderly and frail population, and the uptake of many effective antiarrhythmic therapies in these patients remains the slowest. This European Heart Rhythm Association (EHRA) consensus document focuses on the biology of frailty, common comorbidities, and methods of assessing frailty, in respect to a specific issue of arrhythmias and conduction disease, provide evidence base advice on the management of arrhythmias in patients with frailty syndrome, and identifies knowledge gaps and directions for future research.

Evolution of antithrombotic therapy for patients with atrial fibrillation: The prospective global GLORIA-AF registry program.

OBJECTIVE: To assess baseline characteristics and antithrombotic treatment (ATT) prescription patterns in patients enrolled in the third phase of the GLORIA-AF Registry Program, evaluate predictors of treatment prescription, and compare results with phase II. METHODS: GLORIA-AF is a large, global, prospective registry program, enrolling patients with newly diagnosed nonvalvular atrial fibrillation (AF) at risk of stroke. Patients receiving dabigatran were followed for two years in phase II, and all patients were followed for 3 years in phase III. Phase II started when dabigatran became available; phase III started when the characteristics of patients receiving dabigatran became roughly comparable with those receiving vitamin K antagonists (VKAs). RESULTS: Between 2014 and 2016, 21,241 patients were enrolled in phase III. In total, 82% of patients were prescribed oral anticoagulation ([OAC]; 59.5% novel/nonvitamin K oral anticoagulants [NOACs], 22.7% VKAs). A further 11% of patients were prescribed antiplatelets without OAC and 7% were prescribed no ATT. A high stroke risk was the main driver of OAC prescription. Factors associated with prescription of VKA over NOAC included type of site, region, physician specialty, and impaired kidney function. CONCLUSION: Over the past few years, data from phase III of GLORIA-AF show that OACs have become the standard treatment option, with most newly diagnosed AF patients prescribed a NOAC. However, in some regions a remarkable proportion of patients remain undertreated. In comparison with phase II, more patients received NOACs in phase III while the prescription of VKA decreased. VKAs were preferred over NOACs in patients with impaired kidney function.

Dabigatran versus vitamin K antagonists for atrial fibrillation in clinical practice: final outcomes from Phase III of the GLORIA-AF registry.

BACKGROUND: Prospectively collected, routine clinical practice-based data on antithrombotic therapy in non-valvular atrial fibrillation (AF) patients are important for assessing real-world comparative outcomes. The objective was to compare the safety and effectiveness of dabigatran versus vitamin K antagonists (VKAs) in patients with newly diagnosed AF. METHODS AND RESULTS: GLORIA-AF is a large, prospective, global registry program. Consecutive patients with newly diagnosed AF and CHA2DS2-VASc scores ≥ 1 were included and followed for 3 years. To control for differences in patient characteristics, the comparative analysis for dabigatran versus VKA was performed on a propensity score (PS)-matched patient set. Missing data were multiply imputed. Proportional-hazards regression was used to estimate hazard ratios (HRs) for outcomes of interest. Between 2014 and 2016, 21,300 eligible patients were included worldwide: 3839 patients were prescribed dabigatran and 4836 VKA with a median age of 71.0 and 72.0 years, respectively; > 85% in each group had a CHA2DS2-VASc-score ≥ 2. The PS-matched comparative analysis for dabigatran and VKA included on average 3326 pairs of matched initiators. For dabigatran versus VKAs, adjusted HRs (95% confidence intervals) were: stroke 0.89 (0.59-1.34), major bleeding 0.61 (0.42-0.88), all-cause death 0.78 (0.63-0.97), and myocardial infarction 0.89 (0.53-1.48). Further analyses stratified by PS and region provided similar results. CONCLUSIONS: Dabigatran was associated with a 39% reduced risk of major bleeding and 22% reduced risk for all-cause death compared with VKA. Stroke and myocardial infarction risks were similar, confirming a more favorable benefit-risk profile for dabigatran compared with VKA in clinical practice. Clinical trial registration https://www. CLINICALTRIALS: gov . NCT01468701, NCT01671007.

Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice: GLORIA-AF Registry.

BACKGROUND AND PURPOSE: Prospectively collected data comparing the safety and effectiveness of individual non-vitamin K antagonists (NOACs) are lacking. Our objective was to directly compare the effectiveness and safety of NOACs in patients with newly diagnosed atrial fibrillation (AF). METHODS: In GLORIA-AF, a large, prospective, global registry program, consecutive patients with newly diagnosed AF were followed for 3 years. The comparative analyses for (1) dabigatran vs rivaroxaban or apixaban and (2) rivaroxaban vs apixaban were performed on propensity score (PS)-matched patient sets. Proportional hazards regression was used to estimate hazard ratios (HRs) for outcomes of interest. RESULTS: The GLORIA-AF Phase III registry enrolled 21,300 patients between January 2014 and December 2016. Of these, 3839 were prescribed dabigatran, 4015 rivaroxaban and 4505 apixaban, with median ages of 71.0, 71.0, and 73.0 years, respectively. In the PS-matched set, the adjusted HRs and 95% confidence intervals (CIs) for dabigatran vs rivaroxaban were, for stroke: 1.27 (0.79-2.03), major bleeding 0.59 (0.40-0.88), myocardial infarction 0.68 (0.40-1.16), and all-cause death 0.86 (0.67-1.10). For the comparison of dabigatran vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 1.16 (0.76-1.78), myocardial infarction 0.84 (0.48-1.46), major bleeding 0.98 (0.63-1.52) and all-cause death 1.01 (0.79-1.29). For the comparison of rivaroxaban vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 0.78 (0.52-1.19), myocardial infarction 0.96 (0.63-1.45), major bleeding 1.54 (1.14-2.08), and all-cause death 0.97 (0.80-1.19). CONCLUSIONS: Patients treated with dabigatran had a 41% lower risk of major bleeding compared with rivaroxaban, but similar risks of stroke, MI, and death. Relative to apixaban, patients treated with dabigatran had similar risks of stroke, major bleeding, MI, and death. Rivaroxaban relative to apixaban had increased risk for major bleeding, but similar risks for stroke, MI, and death. REGISTRATION: URL: https://www. CLINICALTRIALS: gov . Unique identifiers: NCT01468701, NCT01671007. Date of registration: September 2013.

Treatment of adult, child and newborn cardiac arrest victims with COVID-19. Recommendations from the Interamerican Society of Cardiology / Sociedad Interamericana de Cardiología (SIAC), Mexican National Cardiologists Association / Asociación Nacional de Cardiólogos de México (ANCAM) and Mexican Society of Cardiology / Sociedad Mexicana de Cardiología (SMC).

La pandemia de COVID-19 ha infligido grandes estragos a la población y en especial al personal de salud. Los esfuerzos de reanimación exigen modificaciones potenciales de las guías internacionales existentes de reanimación cardiopulmonar (RCP) debido al elevado índice de contagiosidad del virus SARS-CoV-2. Se considera que hasta 15% de los casos de COVID-19 tiene una enfermedad grave y 5% padece un trastorno crítico con una mortalidad promedio del 3%, la cual varía según sean el país y las características de los pacientes. La edad y las comorbilidades como la hipertensión arterial, enfermedad cardiovascular, obesidad y diabetes incrementan la mortalidad hasta 24%. También se ha informado un aumento reciente del número de casos de paro cardíaco extrahospitalario (PCEH). Aunque el paro cardíaco (PC) puede ser efecto de factores diversos en estos pacientes, en la mayoría de los casos se ha demostrado que el origen es respiratorio, con muy pocos casos de causa cardíaca. Se debe considerar la indicación de iniciar o continuar las maniobras de RCP por dos razones fundamentales: la posibilidad de sobrevida de las víctimas, que hasta la fecha se ha registrado muy baja, y el riesgo de contagiar al personal de salud, que es muy alto.The COVID-19 pandemic is having a large impact on the general population, but it has taken a specially high toll on healthcare personnel. Resuscitation efforts require potential modifications of the present Cardiopulmonary Resuscitation (CPR) international guidelines because of the transmissibility rate of the new SARS-CoV 2 virus. It has been seen that up to 15% of COVID-19 patients have a severe disease, 5% have a critical form of infection and the mean death rate is 3%, although there are significant differences according to the country that reports it and patients' baseline conditions that include age, presence of arterial hypertension, cardiovascular disease, diabetes or obesity. In these high risk subjects, mortality might go up to 24%. There are also reports of a recent increase in out-of-hospital cardiopulmonary arrest (OHCA) victims. Cardiac arrest (CA) in these subjects might be related to many causes, but apparently, that phenomenon is related to respiratory diseases rather than cardiac issues. In this context, the decision to start or continue CPR maneuvers has to be carefully assessed, because of the low survival rate reported so far and the high contagion risk among healthcare personnel.

Low bleeding and thromboembolic risk with continued dabigatran during cardiovascular interventions: the GLORIA-AF study.

BACKGROUND: Prospective data on nonvitamin-K-antagonist oral anticoagulant (NOAC) management during cardiovascular interventions are limited. We therefore evaluated the safety and effectiveness of uninterrupted dabigatran therapy as well as dabigatran management during atrial fibrillation (AF)-cardioversions, AF-ablations, pacemaker implantations and coronary angiography and/or stenting procedures. METHOD: GLORIA-AF is an international registry programme involving patients with newly diagnosed AF. Dabigatran users were followed for ≤2 years. The primary outcome was occurrence of stroke/systemic embolism and major bleeding ≤8 weeks after a cardiovascular intervention during uninterrupted dabigatran therapy. RESULTS: During the 2-year follow-up, 599 cardiovascular interventions were identified in 479 eligible patients. 412/599 (69%) interventions were performed with uninterrupted dabigatran therapy: 299/354 (84%) AF-cardioversions, 38/89 (43%) AF-ablations, 25/58 (43%) pacemaker implantations, and 50/98 (51%) coronary angiography and/or stenting procedures. During an average follow-up of 8.4 weeks after intervention, one major bleed and one systemic embolic event occurred (risk 0.25% for both outcomes; 95% confidence interval, 0.01%-1.36%). CONCLUSIONS: More than two thirds of the interventions were performed with uninterrupted dabigatran therapy, of which most were AF-cardioversions. Uninterrupted dabigatran therapy was associated with low major bleeding and stroke/systemic embolism risk, supporting the favourable safety and effectiveness profile of dabigatran in clinical practice-based settings.

Anticoagulation Prescription and Outcomes in Relation to Renal Function in Patients with Atrial Fibrillation: Results from GLORIA-AF.

Objective Anticoagulation management in patients with atrial fibrillation (AF) and impaired renal function is challenging. This study aimed to evaluate anticoagulation prescription patterns in relation to renal function and to describe 2-year clinical outcomes among dabigatran users. Methods Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) is an international, prospective, and observational study program involving patients with newly diagnosed AF at risk for stroke. Prescription patterns were assessed by creatinine clearance (CrCl) at enrollment. Dabigatran users were followed for 2 years. Clinical outcomes were standardized for stroke and bleeding risk, based on CHA 2 DS 2 -VASc and HAS-BLED scores, with missing values imputed. Results Baseline CrCl values were available for 12,056 of 15,308 eligible patients (79%). With declining renal function, prescriptions increased for vitamin K antagonists (VKAs) and decreased for dabigatran (30-47% and 34-12%, respectively). The prescription of other non-vitamin K antagonists remained similar across CrCl groups (14-19%). In 4,873 dabigatran users, standardized stroke rates were low across all CrCl groups; 0.58/100 patient-years (95% confidence interval [CI]: 0.30-0.90) in CrCl ≥80 mL/min, 0.85 (95% CI: 0.48-1.21) in CrCl 50 to 79 mL/min, and 0.33 (95% CI: 0.06-1.11) in CrCl 30 to 49 mL/min. Similarly, major bleeding rates were low and numerically increased with declining renal function (0.68/100 patient-years, 95% CI: 0.39-1.03; 0.92, 95% CI: 0.58-1.32; and 1.26, 95% CI: 0.66-1.97, respectively). Conclusion In patients with AF, VKA prescriptions increased and dabigatran prescriptions decreased with declining renal function. Rates of stroke and major bleeding in dabigatran patients remained low across the categories of renal impairment.

Catheter ablation of ventricular tachycardia in patients with electrical storm, with a special focus on patients with Chagas disease.

BACKGROUND: There are few reports on the benefits of catheter ablation (CA) in patients with electrical storm (ES). None of these publications included patients with Chagas disease (ChD). Our aims are to analyze (1) all the cases of ES treated with CA and (2) the subgroup of patients with ChD. METHODS: Prospective analysis of consecutive patients with ES due to monomorphic ventricular tachycardia (VT) treated with CA. RESULTS: We included 38 patients: 28 males; median age of 63.5 (IQR 55-71) years old; ejection fraction (LVEF) 0.30 (0.25-0.40). Sixteen patients (42.1%) had ChD. The patients experienced 21 (15-37) VT episodes and received 7 (3-13) ICD shocks before CA. Forty-six procedures were performed (7 required epicardial access). All patients experienced ES suppression after CA. After 35 (10-64) months of follow-up (1.21 procedures per patient), 23 patients (60.5%) remain free from any VT; 35 patients (92.1%) were free from ES, and 11 patients (28.9%) died from non-arrhythmic causes. One patient underwent heart transplantation. Patients with ChD were younger (60 vs. 67 years old; p = 0.033), significantly more women (50% vs. 9.1%; p = 0.005), and had higher LVEF (0.40 vs. 0.28; p < 0.001) than the other patients. Long-term outcome of ChD patients was similar to that of the overall population. Only age and LVEF independently predicted mortality. CONCLUSION: CA was associated with acute ventricular arrhythmia suppression in all patients with ES. Freedom rates from ES and VT were 92.1% and 60.5% respectively. Despite having a lower-risk clinical profile, patients with ChD had a comparable outcome to that of the other patients.

Effectiveness and safety of dabigatran in Latin American patients with atrial fibrillation: Two years follow up results from GLORIA-AF registry.

BACKGROUND: Real-world data from different regions are needed to support the external validity of controlled trials and assess the impact of new oral anticoagulants (NOAC) in clinical practice. METHODS: "GLORIA-AF" is a large, ongoing, multicenter, global, prospective registry program in patients with newly diagnosed non-valvular atrial fibrillation (NVAF) at risk of stroke. Newly diagnosed patients with NVAF (within 4.5 months) and a CHA2DS2-VASc score ≥ 1 were consecutively enrolled. The study objective was to estimate the incidence rate of stroke and major bleeding after a two year follow up of patients on dabigatran that participated in the "GLORIA-AF" study (Phase II) in Latin America. RESULTS: Latin America included 378 eligible patients that received dabigatran in eight countries (Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, Perú, and Venezuela): 56.3% were male; mean age was 70.3 ± 10.8 years; 43.4% had paroxysmal AF; 36.0% persistent AF and 20.6% permanent AF. Mean CHA2DS2-VASc score was 3.2 ± 1.4; mean HAS-BLED score was 1.2 ± 0.8. Incidence rates for clinical events after 2-years of follow-up per 100 patient-years were as follows: stroke 0.33 (95% CI: 0.04-1.17), major bleeding 0.49 (95% CI: 0.10-1.42) and all-cause death 4.06 (95% CI: 2.63-6.00). Persistence with dabigatran at 6, 12 and 24 months was 91%, 86%, and 80%, respectively. CONCLUSION: These regional data shows the sustained safety and effectiveness of dabigatran over two years of follow-up, consistent with already available evidence. An increase in accessibility and incorporation of NOAC to anticoagulant treatment strategies could potentially have a positive impact on AF stroke prevention in Latin America.

A counterpoint paper: Comments on the electrocardiographic part of the 2018 Fourth Universal Definition of Myocardial Infarction endorsed by the International Society of Electrocardiology and the International Society for Holter and Noninvasive Electrocardiology.

The Fourth Universal Definition of Myocardial Infarction (FUDMI) focuses on the distinction between nonischemic myocardial injury and myocardial infarction (MI), along with the role of cardiovascular magnetic resonance, in order to define the etiology of myocardial injury. As a consequence, there is less emphasis on updating the parts of the definition concerning the electrocardiographic (ECG) changes related to MI. Evidence of myocardial ischemia is a prerequisite for the diagnosis of MI, and the ECG is the main available tool for (a) detecting acute ischemia, (b) triage, and (c) risk stratification upon presentation. This review focuses on multiple aspects of ECG interpretation that we firmly believe should be considered for incorporation in any future update to the Universal Definition of MI.

Characteristics and 2-year outcomes of dabigatran treatment in patients with heart failure and atrial fibrillation: GLORIA-AF.

AIMS: This study aimed to describe baseline characteristics of patients with atrial fibrillation (AF) at risk of stroke with and without history of heart failure (HF) and report 2-year outcomes in the dabigatran-treated subset of a prospective, global, observational study (GLORIA-AF). METHODS AND RESULTS: Newly diagnosed patients with AF and CHA2 DS2 -VASc score ≥ 1 were consecutively enrolled. Baseline characteristics were assessed by the presence or absence of HF diagnosis at enrolment. Incidence rates for outcomes in dabigatran-treated patients were estimated with and without standardization by stroke (excluding HF component) and bleeding risk scores. A total of 15 308 eligible patients were enrolled, including 15 154 with known HF status; of these, 3679 (24.0%) had been diagnosed with HF, 11 475 (75.0%) had not. Among 4873 dabigatran-treated patients, 1169 (24.0%) had HF, and 3658 (75.1%) did not; the risk of stroke was high (CHA2 DS2 -VASc score ≥ 2) for 94.3% of patients with HF and 85.8% without, while 6.0% and 7.0%, respectively, had a high bleeding risk (HAS-BLED ≥ 3). Incidence rates of all-cause death in dabigatran-treated patients with and without HF, standardized for CHA2 DS2 -VASc and HAS-BLED scores, were 4.76 vs. 1.80 per 100 patient years (py), with roughly comparable rates of stroke (0.82 vs. 0.60 per 100 py) and major bleeding (1.20 vs. 0.92 per 100 py). CONCLUSIONS: Patients with AF and history of HF may have greater disease burden at AF diagnosis and increased mortality rates vs. patients without HF. Stroke and major bleeding rates were roughly comparable between groups confirming the long-term safety and effectiveness of dabigatran in patients with HF.

Prevención del stroke en fibrilación auricular. Hallazgos del registro GLORIA-AF / Stroke Prevention In Atrial Fibrillation. Findings From The Gloria-Af Registry

RESUMEN Introducción: El GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) es un registro internacional, prospectivo, en tres fases, para determinar la seguridad y eficacia del dabigatrán en pacientes con fibrilación auricular no valvular recientemente diagnosticada, en riesgo de stroke. La fase II empezó cuando el dabigatrán, el primer anticoagulante oral no antagonista de la vitamina K (NOAC) estuvo disponible. Objetivos: Describir los datos clínicos basales de la fase II en la población general y el seguimiento a 2 años de aquellos que recibieron dabigatrán. Material y Métodos: Se reclutaron un total de 15 644 pacientes, de los cuales 15 308 fueron elegibles y 4873 recibieron dabigatrán. Se analizaron las características de la fibrilación auricular, los hallazgos en el seguimiento y las enfermedades concomitantes. Los datos fueron analizados usando estadísticas descriptivas. Resultados: Del total de pacientes elegibles, el 45,5% eran mujeres, con una edad promedio de 71 (rango intercuartilo: 64-78) años. Los pacientes eran de Europa (47,9%), América del Norte (22,2%), Asia (20,1%), América Latina (6,0%) y Medio Oriente/ África (3,9%). La mayoría se encontraba en alto riesgo de stroke (CHA2DS2-VASc score >2; 86,1%); un 13,9% tuvieron riesgo moderado (CHA2DS2-VASc score >1). El 80,3% recibieron anticoagulantes orales; de ellos, el 47,9% recibieron NOAC y el 32,4%, antagonistas de la vitamina K (VKA); 12,0% recibieron agentes antiagregantes plaquetarios y el 7,6% no recibieron tratamiento antitrombótico. A 2 años de seguimiento, el 70,5% permanecieron en dabigatrán. Conclusiones: Los datos de la fase II del registro GLORIA-AF demostraron que, en FA no valvular, los NOAC han sido ampliamente adoptados en la práctica clínica y fueron más frecuentemente prescriptos que los VKA. No obstante, una gran proporción de pacientes en todo el mundo permanecieron sin tratamiento.

ABSTRACT Background: GLORIA-AF is a prospective, global, 3-phase registry program to determine the safety and effectiveness of dabigatran in patients with newly diagnosed non-valvular atrial fibrillation at risk of stroke. Phase II began when dabigatran, the first non-vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives: To describe phase II baseline clinical data in the general population and 2-year follow-up of those patients treated with dabigatran. Methods: A total of 15,644 patients were enrolled, 15,308 of whom were eligible and 4,873 received dabigatran. Atrial fibrillation disease characteristics, follow-up findings and concomitant diseases were collected. Data were analyzed using descriptive statistics. Results: Of the total eligible patients, 45.5% were female; median age was 71.0 (interquartile range: 64, 78) years. Patients were from Europe (47.9%), North America (22.2%), Asia (20.1%), Latin America (6.0%), and the Middle East/Africa (3.9%). Most had high stroke risk (CHA2DS2-VASc score ≥2; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc =1). Overall, 80.3% received oral anticoagulants, of whom 47.9% received NOACs and 32.4% vitamin K antagonists (VKA); 12.0% received anti-platelet agents; and 7.6% received no antithrombotic treatment. At 2-year follow-up, 70.5% remained on dabigatran. Conclusions: Data from GLORIA-AF phase II showed that in non-valvular AF, NOACs have been highly adopted in clinical practice, becoming more frequently prescribed than VKAs. Worldwide, however, a large proportion of patients remain undertreated.

Persistence with Anticoagulation for Atrial Fibrillation: Report from the GLORIA-AF Phase III 1-Year Follow-up.

BACKGROUND: We aimed to assess the extent to which drug persistence is better with non-vitamin K antagonist oral anticoagulants (NOACs) than vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients and to estimate the difference in therapy persistence depending on NOAC dosing regimen (once daily (QD) vs. twice daily (BID)). METHODS: Consecutive patients were followed for 1 year in phase III of the GLORIA-AF registry. Drug persistence was defined as the use of OAC without any discontinuation in >30 days or switching to alternative therapy. RESULTS: Among 21,109 eligible patients in phase III, 17,266 patients who were prescribed OAC at baseline and those who took ≥1 OAC dose were included. The 1-year proportion of patients receiving NOAC and VKA who persisted on treatment was 80% and 75%, respectively. The 1-year persistence with NOACs BID and NOACs QD was 81% and 80%, respectively. Female gender, hypertension, older age, alcohol use, permanent, asymptomatic, and minimally symptomatic AF were associated with better OAC persistence. Region, medication usage predisposing to bleeding, being a current smoker, treatment reimbursement, and proton pump inhibitors were associated with lower OAC persistence. CONCLUSIONS: Drug persistence was higher with NOACs (1-year persistence was 80%) than with VKAs (75%). There was little difference in 1-year persistence between NOAC dosing regimens.

Stroke prevention in atrial fibrillation changes after dabigatran availability in China: The GLORIA-AF registry.

BACKGROUND: Until the approval of dabigatran etexilate, treatment choices for stroke prevention in patients with atrial fibrillation (AF) were vitamin K antagonists (VKAs) or antiplatelet drugs. This analysis explored whether availability of non-vitamin K antagonist oral anticoagulants post-dabigatran approval was associated with changing treatment patterns in China. METHODS: Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) collected data on antithrombotic therapy choices for patients with newly diagnosed nonvalvular AF at risk for stroke. In China, enrollment in phase 1 (before dabigatran approval) and phase 2 (after dabigatran approval) occurred from 2011 to 2013 and 2013 to 2014, respectively. Analyses were restricted to sites within China that contributed patients to both phases. The weighted average of the site-specific results was estimated for standardization. Sensitivity analyses used multiple regression. RESULTS: Thirteen sites participated in both phase 1 (419 patients) and phase 2 (276 patients), 76.1% and 16.0% were known to be at high risk for stroke (CHA2DS2-VASc ≥2) and bleeding (HAS-BLED ≥3); 55.5% were male. In phase 1, 16.7%, 61.6%, and 21.7% of patients were prescribed oral anticoagulants (OACs), antiplatelet agents, and no treatment, respectively. Respective proportions were 26.4%, 40.6%, and 33.0% in phase 2. The absolute increase in the site-standardized proportion of patients prescribed OACs after dabigatran availability was 9.9% (95% confidence interval [CI]: 3.7%-16.0%). There was a standardized 17.3% (95% CI: -24.3% to -10.4%) absolute decrease in antiplatelet agent use. CONCLUSIONS: There was an increase in OAC and decrease in antiplatelet agent prescription since dabigatran availability in China. However, a large proportion of AF patients at risk for stroke remained untreated.

A counterpoint paper: Comments on the electrocardiographic part of the 2018 Fourth Universal Definition of Myocardial Infarction.

The Fourth Universal Definition of Myocardial Infarction (FUDMI) [published simultaneously in 2018 in numerous journals including Circulation, Journal of the American College of Cardiology and European Heart Journal] focuses mainly on the distinction between non-ischemic myocardial injury and myocardial infarction (MI), along with the role of cardiovascular magnetic resonance, in order to define the etiology of myocardial injury. As a consequence, there is less emphasis on updating the parts of the definition concerning the electrocardiographic (ECG) changes related to MI. Evidence of myocardial ischemia is a prerequisite for the diagnosis of MI and the ECG is the main available tool for i) detecting acute ischemia, ii) triage and iii) risk stratification upon presentation. This review focuses on multiple aspects of ECG interpretation that we firmly believe should be considered for incorporation in any future update to the Universal Definition of MI. Our counterpoint view is that: a) the use of the ECG following coronary artery bypass surgery should be better explored and defined; b) the emphasis in the FUDMI on convex versus concave ST-elevation, which is questionable, should be balanced by the fact that many patients with true ST-elevation MI (STEMI) present with a concave form of ST elevation; c) reciprocal ST-depression in STEMI caused by right coronary artery or left circumflex artery occlusion, should be set against the fact that not all anterior STEMIs present with reciprocal ST-depression which can also be seen in cardiomyopathy and left ventricular hypertrophy; d) the "posterior" leads V7-V9 should be placed on a horizontal line from V4, rather than follow the 5th intercostal space; e) ST-depression in V1-V3 is not a manifestation of ischemia of the basal inferior segment, placed horizontally; f) Interpreting ST-T changes in patients with conduction abnormalities and pacemakers should be further defined.

Antithrombotic treatment for newly diagnosed atrial fibrillation in relation to patient age: the GLORIA-AF registry programme.

AIMS: To assess antithrombotic therapy choices in relation to patient age in a large, global registry on atrial fibrillation (AF). METHODS AND RESULTS: Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) is an international programme involving patients with newly diagnosed AF and ≥1 risk factors for stroke. We used Phase II data (from November 2011 through December 2014), which commenced immediately following first non-vitamin K antagonist oral anticoagulants (NOACs) approval in participating countries. Of 15 092 patients (mean age 70.5 ± 11.0 years), enrolled at 982 centres, 26.9% were aged <65 years, 33.9% 65-74, 30.5% 75-84, and 8.6% ≥85 years old. Oral anticoagulant (OAC) use was 73.5%, 81.4%, 83.3%, and 82.3% (overall NOACs use was 44.4%, 49.7%, 48.7%, and 45.6%) for those aged <65, 65-74, 75-84 and ≥85 years, respectively. Corresponding proportions for antiplatelet monotherapy and no treatment were: 16.2% and 10.2%; 11.2% and 7.3%; 10.0% and 6.5%; 10.5% and 7.0%, respectively. Of those aged 65-74, 75-84, and ≥85 years, respectively, 83.7, 86.8 and 85.4% received OAC unless bleeding risk was high (HAS-BLED ≥3), whereby 64.1%, 63.5%, and 64.5% were anticoagulated, and 31.1%, 30.3%, and 31.3% received antiplatelets only. Of patients ≥85 years, OAC use was 88.1% in Europe (NOAC 45.1%), 79.5% in North America (NOAC 44.8%), and 54.1% in Asia (NOAC 40.2%). CONCLUSION: Despite geographic differences in OAC use, neither OAC nor NOAC uptake was lower for patients ≥85 years old compared with younger patients. Although the majority of patients was prescribed OAC at all ages, nearly one-third received antiplatelet monotherapy when bleeding risk was increased. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01468701.

Dabigatran Persistence and Outcomes Following Discontinuation in Atrial Fibrillation Patients from the GLORIA-AF Registry.

Prospective studies evaluating persistence to nonvitamin K antagonist oral anticoagulants in patients with atrial fibrillation are needed to improve our understanding of drug discontinuation. The study objective was to evaluate if and when patients with newly diagnosed atrial fibrillation stop dabigatran treatment and to report outcomes following discontinuation. Patients prescribed dabigatran in diverse clinical practice settings were consecutively enrolled and followed for 2 years. Dabigatran persistence over time, reasons for discontinuation, and outcomes post discontinuation were assessed. Of 4,859 patients, aged 70.2 ± 10.4 years, 55.7% were male. Overall 2-year dabigatran persistence was 70.9% (95% confidence interval [CI] 69.6 to 72.2). Persistence probability was lower in the first 6-month period (83.7% [82.7 to 84.8]) than in subsequent periods for patients on dabigatran at the start of each period (6 to 12 months, 92.5% [91.6 to 93.3]; 12 to 18 months, 95.1% [94.3 to 95.8]; 18 to 24 months, 96.3% [95.6 to 96.9]). Of 1,305 patients (26.9%) who discontinued dabigatran, adverse events were reported as the reason for discontinuation in 457 (35.0%). Standardized stroke incidence rate post discontinuation (per 100 patient-years) in patients discontinuing without switching to another oral anticoagulant was 1.76 (95% CI 0.89 to 2.76) and 1.02 (95% CI 0.43 to 1.76) in those who switched, consistent with the expected benefit of remaining on treatment. Patients persistent with treatment at 1 year had >90% probability of remaining persistent at 2 years suggesting clinical interventions to improve persistence should be focused on the early period following treatment initiation.

Safety and effectiveness of dabigatran at 2 years: Final outcomes from Phase II of the GLORIA-AF registry program.

GLORIA-AF is a large, ongoing, prospective, global registry program run in 3 phases, assessing long-term safety and effectiveness of dabigatran etexilate (dabigatran) in patients with newly diagnosed atrial fibrillation (AF) in clinical practice. This report provides the final analysis of 2-year clinical outcomes of the full cohort of 4873 patients prescribed dabigatran and followed for a mean of 18.0 +/- 9.4 months out of the 15,308 eligible patients enrolled in Phase II (2011-2014). The overall incidence rates per 100 person-years were: stroke 0.65 (95% CI 0.48-0.87), major bleeding 0.97 (0.76-1.23) and myocardial infarction (MI) 0.50 (0.35-0.69), with observed event rates broadly consistent in all study regions, which confirms the sustained safety and effectiveness of dabigatran over 2 years of observation in clinical practice.