Elliott M Antman

• Partners HealthCare

Background Epistaxis is common with antithrombotic therapy and is often troublesome to patients, yet its frequency, severity, and outcomes are poorly characterized. Methods and Results Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48 (ENGAGE AF‐TIMI 48) randomized 21 105 patie...

Background: The ability of polygenic risk scores (PRS) to predict heart failure (HF) beyond classic risk factors is unclear. Aims: To evaluate the risk of a HF PRS with incident hospitalization for HF (HHF) in patients with established cardiovascular disease. Methods: We analyzed a 59 SNP HF PRS (HERMES collaboration, Henry et al) in genotyped pati...

Background: Prior data suggest the MI risk may be higher with paroxysmal AF (PAF) vs. non-paroxysmal AF (non-PAF). Proposed mechanisms include tachycardia-induced oxidative stress (via LOX-1) with microvascular flow abnormalities, ischemia downstream of a fixed coronary obstruction, and plaque rupture. Methods: We compared MI rates in pts with PAF...

Background Atrial Fibrillation (AF) poses a significant risk for both ischemic stroke and systemic embolic events (SEE). While the effectiveness of NOAC in preventing ischemic stroke is well-established, there is a lack of detailed analyses specifically characterizing SEE, which constitutes 5- 10% of all embolic events. Purpose To study the clinic...

Background Randomized data comparing clinical outcomes of atrial fibrillation (AF) patients with Asian vs non-Asian races are limited. Methods Using the COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) database (data from RE-LY, ROCKET AF, ARISTO...

Importance In older patients with atrial fibrillation who take anticoagulants for stroke prevention, bleeding is increased compared with younger patients, thus, clinicians frequently prescribe lower than recommended doses in older patients despite limited randomized data. Objective To evaluate ischemic and bleeding outcomes in patients 80 years an...

BACKGROUND Cardiovascular trials often use a composite end point and a time-to-first event model. We sought to compare edoxaban versus warfarin using the win ratio, which offers data complementary to time-to-first event analysis, emphasizing the most severe clinical events. METHODS ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next G...

Importance Polygenic risk scores (PRSs) have proven to be as strong as or stronger than established clinical risk factors for many cardiovascular phenotypes. Whether this is true for aortic stenosis remains unknown. Objective To develop a novel aortic stenosis PRS and compare its aortic stenosis risk estimation to established clinical risk factors...

BACKGROUND The efficacy and safety of non–vitamin-K antagonist oral anticoagulants (NOACs) across the spectrum of body mass index (BMI) and body weight (BW) remain uncertain. METHODS We analyzed data from COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibril...

Background The efficacy and safety of NOAC versus warfarin (W) may differ in AF pts receiving antiplatelet therapy (APT) at baseline. Moreover, prior individual trial-specific analyses examining the treatment effect of NOAC vs. W as a function of APT are underpowered for interaction testing. Purpose We evaluated outcomes by randomized anticoagulan...

Background: Coronary artery disease (CAD) polygenic risk scores (PRS) may improve risk stratification, but whether performance differs by ASCVD status remains unclear. Purpose: To compare the predictive ability of a CAD PRS for coronary events in pts with ASCVD and prior event, ASCVD without event, and without overt ASCVD. Methods: We studied genot...

Abbreviations: Obstructive sleep apnea (OSA), atrial fibrillation (AF), home sleep test (HST), apnea-hypopnea index (AHI), continuous positive airway pressure (CPAP), Epworth Sleepiness Scale (ESS), Center of Excellence (COE), Mayo AF-Specific Symptom Inventory (MAFSI), Atrial Fibrillation Effect Quality of Life (AFEQT), body-mass index (BMI), oxy...

There is an extraordinary and increasing global burden of atrial fibrillation (AF) and obstructive sleep apnea (OSA), two conditions which frequently accompany one another and which share underlying risk factors. Whether a causal pathophysiologic relationship connects OSA to the development and/or progression of AF, or whether shared risk factors p...

Aims: Cardiac functional and structural remodeling in patients with atrial fibrillation (AF) contributes to development of heart failure (HF) as their major cardiovascular comorbidity. Circulating biomarkers may reflect these cardiac alterations. Methods and results: ENGAGE AF-TIMI 48 was a randomized trial of edoxaban vs warfarin in 21,105 pati...

Background: The risks of heart failure (HF) events compared with stroke/systemic embolic events (SEE) or major bleeding (MB) in heart failure with reduced ejection fraction (HFrEF) vs heart failure with preserved ejection fraction (HFpEF) in a large atrial fibrillation (AF) population have not been well-studied. Objectives: This study sought to...

Introduction: Aortic stenosis (AS) is the most common valvular heart disease. Polygenic risk scores (PRS) use common genetic variants to enhance risk prediction for disease but have not yet been applied in AS. Methods: We generated an AS genetic risk score using summary data from a recently performed GWAS in the Million Veteran Program and score se...

Clinical time-to-event studies are dependent on large sample sizes, often not available at a single institution. However, this is countered by the fact that, particularly in the medical field, individual institutions are often legally unable to share their data, as medical data is subject to strong privacy protection due to its particular sensitivi...

Purpose of Review The scientific consensus on which global health organizations base public health policies is that high sodium intake increases blood pressure (BP) in a linear fashion contributing to cardiovascular disease (CVD). A moderate reduction in sodium intake to 2000 mg per day helps ensure that BP remains at a healthy level to reduce the...

There has been an increase in the prevalence of cardiovascular diseases among young adults in the United States that has been attributed, in part, to a rise in overweight and obesity, use of combustible tobacco and unhealthy diet and exercise patterns. These factors are influenced further by socioeconomic status and other social determinants of hea...

Background: To compare the efficacy and safety of edoxaban vs. warfarin in high-risk subgroups. Methods ENGAGE AF-TIMI 48 was a multicenter randomized, double-blind, controlled trial in 21,105 patients with atrial fibrillation (AF) within 12 months and CHADS2 score >2 randomized to higher-dose edoxaban regimen (HDER) 60 mg/reduced 30 mg, lower-dose...

Aims In patients with atrial fibrillation (AF), peripheral artery disease (PAD) is associated with higher rates of stroke and bleeding. Both higher-dose edoxaban (60/30mg) and lower-dose edoxaban (30/15) were non-inferior to warfarin for stroke/systemic embolism (SEE) and significantly reduced major bleeding in AF patients in the ENGAGE-AF TIMI 48...

Background Studies relying on self-reported sleep data suggest that there is an association between short and long sleep duration and less than ideal cardiovascular health. Evidence regarding the feasibility of using digital health devices to measure sleep duration and assess its relationship to ideal cardiovascular health are lacking. The objectiv...

Background Epistaxis is common with antithrombotic therapy yet under-investigated in cardiovascular clinical trials and observational studies. These bleeding events are often troublesome to patients and may lead to anticoagulant discontinuation. Purpose To describe the frequency, severity, and outcomes of epistaxis in patients with atrial fibrilla...

Background The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy. Methods Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardio...

Aims We investigated whether patients with atrial fibrillation (AF) demonstrate detectable changes in biomarkers including high-sensitivity troponin T (hsTnT), N-terminal B-type natriuretic peptide (NT-proBNP), and growth differentiation factor-15 (GDF-15) over 12 months and whether such changes from baseline to 12 months are associated with the su...

Background: In the ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis In Myocardial Infarction 48) trial, the lower dose edoxaban regimen (LDER) and the higher dose edoxaban regimen (HDER) were noninferior to well-managed warfarin for stroke prevention in atrial fibrillation. Objectives...

Background: Women are underrepresented across cardiovascular clinical trials. Whether women are more likely than men to prematurely discontinue study drug or withdraw consent once enrolled in a clinical trial is unknown. Methods: Eleven phase 3/4 TIMI (Thrombolysis in Myocardial Infarction) trials were included (135 879 men and 51 812 women [28%...

Background Female sex is an independent risk factor for stroke and systemic embolic events in patients with atrial fibrillation. This study aimed to examine the efficacy and safety profile of edoxaban in women versus men. Methods The ENGAGE AF-TIMI 48 trial (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolys...

Introduction The efficacy and safety of the oral factor Xa inhibitor edoxaban compared to warfarin stratified by CHA2DS2VASc scores have not been described. Methods The ENGAGE AF-TIMI 48 trial randomized patients with atrial fibrillation to once-daily edoxaban or warfarin. We classified patients based on CHA2DS2VASc score and compared pharmacokine...

Intracranial hemorrhage (ICH) is a known risk of oral anticoagulation; delineating ICH attributes may provide nuanced guidance regarding atrial fibrillation management. We evaluated ICH characteristics and outcomes from Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE A...

Background: Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) that are associated with an increased risk of stroke. We sought to determine whether a genetic risk score (GRS) could identify subjects at higher risk for ischemic stroke after accounting for traditional clinical risk factors in five trials across the...

Background The ENGAGE AF–TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48) demonstrated noninferiority of once-daily 60 mg (30 mg dose-reduced) edoxaban compared with warfarin for prevention of stroke/systemic embolism in patients with atrial fibrillation. No pre...

Background Patients with atrial fibrillation (AF) have progressive cardiac structural changes that may be manifest by biomarkers of myocardial injury and hemodynamic stress. Baseline values of hsTnT (high-sensitivity troponin T), and NT-proBNP (N-terminal pro-brain natriuretic peptide) are associated with stroke risk and GDF-15 (growth differentiat...

Background In the phase 3 RCT ENGAGE AF-TIMI 48, both the higher-dose (HDER/edoxaban 60/30mg) and lower-dose edoxaban regimen (LDER/edoxaban 30/15mg) were non-inferior to well-managed warfarin for the prevention of stroke or systemic embolic events in patients with atrial fibrillation (AF). While LDER was associated with a 41% relative increase in...

Aims Concomitant atrial fibrillation (AF) and diabetes mellitus (DM) increases risk of stroke and systemic embolic events. This meta-analysis assessed the benefit/risk balance of non-vitamin K antagonist oral anticoagulants (NOACs) vs warfarin, and explored whether there was effect modification by DM or heterogeneity in outcomes between NOACs in pa...

Background: The effects of anticoagulants at extremes of body weight (BW) are not well described. The aim of this study was to analyze the pharmacokinetics/pharmacodynamics and clinical outcomes in patients randomized to warfarin, higher dose edoxaban (HDER), and lower dose edoxaban (LDER) regimens at extremes of BW in ENGAGE AF-TIMI 48. Methods...

The preferred contemporary approach to the management of stable ischemic heart disease, also referred to as chronic coronary syndrome,¹ is not well defined. Two strategies are commonly used.² The conservative strategy uses guideline-based medical therapy, including antianginal drugs as well as disease-modifying agents, such as hypolipidemic, antith...

Background Recent emphasis on reduced duration and/or intensity of antiplatelet therapy following percutaneous coronary intervention (PCI) irrespective of indication for PCI may fail to account for the substantial risk of subsequent nontarget lesion events in acute coronary syndrome (ACS) patients. Objectives The authors sought to examine the effe...

Background Safe administration of warfarin presents challenges due to a narrow therapeutic INR range and significant variability in inter-individual dose response. Bleeding secondary to warfarin use is a leading cause of hospitalization. Methods Five warfarin dosing algorithms were assessed for accuracy of predicted compared to the INR target dose...

Background: Diabetes mellitus is an independent risk factor for stroke and atrial fibrillation. Therefore, the risk/benefit profile of the oral factor Xa inhibitor edoxaban stratified by diabetes is of clinical interest. Methods: 21,105 patients enrolled in ENGAGE AF-TIMI 48 were stratified into 2 pre-specified groups: without (N = 13,481) and w...

Background: It remains disputed whether women are at excess risk of adverse outcomes versus men after non-ST-segment elevation acute coronary syndromes (NSTEACS) or whether differences are explained by discordant risk factors. Objectives: A sex-specific analysis of cardiovascular outcomes after NSTEACS across trials conducted by the Thrombolysis...

Introduction: Non-vitamin K antagonist oral anticoagulants represent a new option for prevention of embolic events in patients with atrial fibrillation (AF). However, little is known about the impact of non-cardiac comorbidities on the efficacy and safety profile of these drugs. Methods: In a post-hoc analysis of the ENGAGE AF-TIMI 48 trial, we...

Aims: The present study aimed to assess the association between left atrial (LA) structure and function and the risk for cardiovascular (CV) death or heart failure (HF) hospitalization in a population with atrial fibrillation (AF). Methods and results: In a prospective echocardiographic substudy of the Effective Anticoagulation with Factor Xa Ne...

Background: Numerous scales exist for the classification of major bleeding events. Limited data compare the most commonly used bleeding scales within a single at-risk cohort of patients with atrial fibrillation. Here, we analyze bleeding outcomes according to the ISTH (International Society on Thrombosis and Hemostasis), TIMI (Thrombolysis in Myoc...

Background The impact on outcomes of oral anticoagulants in pts at extremes of body weight have not been well-characterized. Aim To analyse the outcomes of pts with atrial fibrillation (AF) enrolled in ENGAGE AF-TMI 48 randomized to warfarin (W) targeting INR 2.0–3.0, higher (HDE) or lower dose regimens of edoxaban (LDE), focusing on subgroups of...

Introduction Atrial Fibrillation (AF) is associated with increased risk of cardiovascular (CV) morbidity and mortality. Heart Failure (HF) represents the most common CV complication, more common than thromboembolic events. Purpose We aimed to determine clinical factors associated with HF hospitalization and mortality in a contemporary cohort of pa...

Background The double-blind OMEGA-REMODEL placebo-controlled randomized trial of high-dose omega-3 fatty acids (O-3FA) post-acute myocardial infarction (AMI) reported improved cardiac remodeling and attenuation of non-infarct myocardial fibrosis. Fatty acid desaturase 2 (FADS2) gene cluster encodes key enzymes in the conversion of essential omega-3...

Hypertension is a risk factor for both stroke and bleeding in patients with atrial fibrillation. Data are sparse regarding the interaction between blood pressure and the efficacy and safety of direct oral anticoagulants. In the ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in M...

Background: Patients with liver disease have increased risk of thrombosis and bleeding but are typically excluded from trials of direct oral anticoagulant agents. Objectives: This study evaluated the pharmacokinetics (PK), pharmacodynamics (PD), clinical efficacy and safety of edoxaban versus warfarin in patients with atrial fibrillation (AF) an...

Aims: To investigate the relationship between body mass index (BMI) and outcomes in patients with atrial fibrillation (AF). Methods and results: In the ENGAGE AF-TIMI 48 trial, patients with AF were randomized to warfarin (international normalized ratio 2.0-3.0) or edoxaban. The cohort (N = 21 028) included patients across BMI categories (kg/m2)...

Aims: Prior studies suggested that the risks of ischaemic stroke and bleeding in patients of Asian race with atrial fibrillation (AF) may be higher than that of non-Asians. In the analysis of ENGAGE AF-TIMI 48 trial, we compared clinical outcomes, edoxaban concentration, and anti-factor Xa (anti-FXa) activity, between Asian and non-Asian races. M...

Background We aimed to determine the change in treatment strategies and times to treatment over the first 5 years of the Mission: Lifeline program. Methods and Results We assessed pre‐ and in‐hospital care and outcomes from 2008 to 2012 for patients with ST ‐segment–elevation myocardial infarction at US hospitals, using data from the National Card...

Aims: Pacemaker, implantable cardioverter-defibrillator, and cardiac resynchronization therapy device implantations and generator changes are frequently performed in patients receiving direct oral anticoagulants. In an exploratory analysis, we investigated the outcome of patients undergoing such device procedures in the ENGAGE AF-TIMI 48 trial. M...

Background: The ABC (age, biomarker, clinical history)-stroke and ABC-bleeding risk scores incorporate clinical variables and cardiovascular biomarkers to estimate risk of stroke or systemic embolic events and bleeding, respectively, in patients with atrial fibrillation. These scores have been proposed for routine clinical use, but their performan...

Background: Patients with atrial fibrillation and concomitant coronary artery disease (CAD) are at higher risk for myocardial infarction or cardiovascular death, often require antiplatelet therapy and are therefore exposed to an increased risk of bleeding. This meta-analysis aimed to compare the efficacy and safety profile of non-vitamin K antagon...

Background: There is limited information about the use of antithrombotic therapies and outcomes of Latin American (LatAm) subjects with atrial fibrillation. The global ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation Atrial Fibrillation-Thrombolysis In Myocardial Infarction 48) trial compared the efficacy and safety of e...

Aims: Although presenting features and early sequelae of non-ST-segment elevation acute coronary syndromes (NSTE-ACS) are well described, less is known about longer-term risks and modes of death. The purpose of this study was to characterize modes of death following NSTE-ACS in clinical trial populations. Methods and results: We evaluated 66 252...

Background Anticoagulation in patients with malignancy and atrial fibrillation is challenging because of enhanced risks for thrombosis and bleeding and the frequent need for invasive procedures. Data on direct oral antagonists in such patients are sparse. Methods and Results The ENGAGE AF‐TIMI 48 (Effective Anticoagulation With Factor Xa Next Gene...

Background: The relative efficacy and safety profile of the oral Factor Xa inhibitor edoxaban compared with warfarin in patients with atrial fibrillation and established coronary artery disease (CAD) has not been analyzed. Materials and methods: In the ENGAGE AF-TIMI 48 trial, two edoxaban regimens were compared with warfarin in 21,105 patients...

Background -We previously reported exogenous anti-factor Xa activity as a pharmacokinetic surrogate marker for edoxaban plasma concentrations. Inhibition of endogenous FXa activity is a more biologically relevant pharmacodynamic measure of edoxaban activity. Here we describe the value of endogenous FXa activity as a pharmacodynamic marker linking e...

Background Peri-operative management of anticoagulated patients with atrial fibrillation (AF) is challenging. To gain information on the peri-operative management of edoxaban, we compared outcomes in patients on warfarin or edoxaban enrolled in ENGAGE AF-TIMI 48 who underwent a surgery or invasive procedure. Methods Data from patients undergoing th...

Background The ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis In Myocardial Infarction) compared higher-dose edoxaban regimen (HD-ER) and lower-dose edoxaban regimen with well-managed warfarin in 21 105 patients with atrial fibrillation. The risk factors and clinical impact of g...

Background: Patients with atrial fibrillation (AF) who interrupt anticoagulation are at high risk of thromboembolism and death. Methods and results: Patients enrolled in the ENGAGE AF-TIMI 48 trial (randomized comparison of edoxaban vs. warfarin) who interrupted study anticoagulant for >3 days were identified. Clinical events (ischemic stroke/sy...

El texto completo y el documento complementario de casos clínicos de la presente actualización se encuentran disponibles en: www.escardio.org/Guidelines/Clinical-Practice-Guidelines/2017-focused-update-on-dual-antiplatelet-therapy-dapt.

Net US spending on pharmaceuticals reached $309.5 billion in 2015, an 8.5% increase from the year before, and is expected to reach between $370 and $400 billion by 2020. These current and projected levels have raised serious concerns by policy makers, providers, payers, and patient groups that they are unsustainable and threaten the affordability o...

Table S1. Demographic and Clinical Characteristics Between Patients in the Study Population and Those Excluded From Analysis* Table S2. Quality of Life Compliance by Bleeding Status Appendix S1. The Members of the Operations, Executive, Steering, Data Monitoring, Clinical Events Committees, Countries, Participating Centers, Principal Investigator...

Background The impact of different types of extracranial bleeding events on health‐related quality of life and health‐state utility among patients with atrial fibrillation is not well understood. Methods and ResultsThe ENGAGE AF‐TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infar...

Table S1. Baseline Characteristics by Baseline HF Status and Digoxin Use Table S2. Clinical Outcomes by Digoxin Use and Type of HF at Baseline Table S3. Digoxin Use in Patients Without HF at Baseline Using Digoxin as a Time‐Variant Covariate (Digoxin “on” or Digoxin “on/off” Methods*)

Background Atrial fibrillation (AF) ablation procedures are increasingly being performed in patients receiving direct oral anticoagulants (DOACs). Experience regarding the safety of edoxaban in this context is limited. In an exploratory analysis we therefore investigated the outcome of patients undergoing transcatheter AF ablation in the ENGAGE AF-...

Background: The use of non-vitamin K antagonist oral anticoagulants (NOACs) instead of vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and coexisting valvular heart disease (VHD) is of substantial interest. Objectives: This study explored outcomes in patients with AF with and without VHD in the ENGAGE AF-TIMI 48 (Effective...

Atrial fibrillation (AF) and valvular heart disease (VHD) frequently coexist and independently increase mortality1. Bioprosthetic valve implantation (surgical or transcatheter), is a common, increasingly utilized treatment for VHD2. Patients with AF and bioprosthetic valves require anticoagulation to prevent thromboembolic events. Non-vitamin K ora...

Aims: The choice between initiating a non-vitamin K antagonist oral anticoagulant (NOAC) and a vitamin K antagonist (VKA) in patients with atrial fibrillation (AF) may be challenging. To assist in this decision, we developed a risk score to identify patients for whom a therapeutic benefit of NOACs over VKA is predicted. Methods and results: ENGA...