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Showing papers by "Elliott M. Antman published in 2015"


Journal ArticleDOI
TL;DR: In this article, higher-dose and lower-dose edoxaban were compared with warfarin in patients with atrial fibrillation in the ENGAGE AF-TIMI 48 trial.

343 citations


Journal ArticleDOI
TL;DR: The 4F-PCC dose-dependently reversed the effects of edoxaban (60 mg), with complete reversal of bleeding duration and endogenous thrombin potential and partial reversal of prothrombin time following 50 IU/kg.
Abstract: Background—The oral factor Xa inhibitor edoxaban has demonstrated safety and efficacy in stroke prevention in patients with atrial fibrillation and in the treatment and secondary prevention of venous thromboembolism. This study investigated the reversal of edoxaban’s effects on bleeding measures and biomarkers by using a 4-factor prothrombin complex concentrate (4F-PCC). Methods and Results—This was a phase 1 study conducted at a single site. This was a double-blind, randomized, placebo-controlled, 2-way crossover study to determine the reversal effect of descending doses of 4F-PCC on bleeding duration and bleeding volume following edoxaban treatment. A total of 110 subjects (17 in part 1, 93 in part 2) were treated. Intravenous administration of 4F-PCC 50, 25, or 10 IU/kg following administration of edoxaban (60 mg) dose-dependently reversed edoxaban’s effects on bleeding duration and endogenous thrombin potential, with complete reversal at 50 IU/kg. Effects on prothrombin time were partially reversed at...

233 citations


Journal ArticleDOI
TL;DR: After 90 days, the reduction in bleeding risk with edoxaban versus warfarin was similarly beneficial across genotypes, and treatment with Edoxaban reduced bleeding more so in sensitive and highly sensitive responders than in normal responders.

149 citations


Journal ArticleDOI
TL;DR: Pre-clinical administration of diltiazem is safe and may improve early LV remodeling in HCM, and this novel strategy merits further exploration.
Abstract: Objectives The study sought to assess the safety, feasibility, and effect of diltiazem as disease-modifying therapy for at-risk hypertrophic cardiomyopathy (HCM) mutation carriers. Background HCM is caused by sarcomere mutations and characterized by left ventricular hypertrophy (LVH) with increased risk of heart failure and sudden death. HCM typically cannot be diagnosed early in life, although subtle phenotypes are present. Animal studies indicate that intracellular calcium handling is altered before LVH develops. Furthermore, early treatment with diltiazem appeared to attenuate disease emergence. Methods In a pilot, double-blind trial, we randomly assigned 38 sarcomere mutation carriers without LVH (mean 15.8 years of age) to therapy with diltiazem 360 mg/day (or 5 mg/kg/day) or placebo. Treatment duration ranged from 12 to 42 months (median 25 months). Study procedures included electrocardiography, echocardiography, cardiac magnetic resonance imaging, and serum biomarker measurement. Results Diltiazem was not associated with serious adverse events. Heart rate and blood pressure did not differ significantly between groups. However, mean left ventricular (LV) end-diastolic diameter improved toward normal in the diltiazem group but decreased further in controls (change in z-scores, +0.6 vs. –0.5; p Conclusions Pre-clinical administration of diltiazem is safe and may improve early LV remodeling in HCM. This novel strategy merits further exploration. (Treatment of Preclinical Hypertrophic Cardiomyopathy With Diltiazem; NCT00319982).

139 citations


Journal ArticleDOI
TL;DR: Patients randomized to the LDE treated with amiodarone at the time of randomization demonstrated a significant reduction in ischaemic events vs. warfarin when compared with those not on amioarone, while preserving a favourable bleeding profile.
Abstract: Background In the ENGAGE AF-TIMI 48 trial, the higher-dose edoxaban (HDE) regimen had a similar incidence of ischaemic stroke compared with warfarin, whereas a higher incidence was observed with the lower-dose regimen (LDE). Amiodarone increases edoxaban plasma levels via P-glycoprotein inhibition. The current pre-specified exploratory analysis was performed to determine the effect of amiodarone on the relative efficacy and safety profile of edoxaban. Methods and results At randomization, 2492 patients (11.8%) were receiving amiodarone. The primary efficacy endpoint of stroke or systemic embolic event was significantly lower with LDE compared with warfarin in amiodarone treated patients vs. patients not on amiodarone (hazard ratio (HR) 0.60, 95% confidence intervals (CIs) 0.36-0.99 and HR 1.20, 95% CI 1.03-1.40, respect- ively;P interaction ,0.01). In patients randomized to HDE, no such interaction for efficacy was observed (HR 0.73, 95% CI 0.46-1.17 vs. HR 0.89, 95% CI 0.75-1.05, P interaction ¼ 0.446). Major bleeding was similar in patients on LDE (HR 0.35, 95% CI 0.21-0.59 vs. HR 0.53, 95% CI 0.46-0.61,P interaction ¼ 0.131) and HDE (HR 0.94, 95% CI 0.65-1.38 vs. HR 0.79, 95% CI 0.69-0.90, P interaction ¼ 0.392) when compared with warfarin, independent of amiodarone use. Conclusions Patients randomized to the LDE treated with amiodarone at the time of randomization demonstrated a significant reduction in ischaemic events vs. warfarin when compared with those not on amiodarone, while preserving a favourable bleeding profile. In contrast, amiodarone had no effect on the relative efficacy and safety of HDE.

79 citations


Journal ArticleDOI
TL;DR: The American Heart Association/American Stroke Association will promote science-based best practices for comprehensive workplace wellness programs and establish benchmarks for a national workplace wellness recognition program to assist employers in applying the best systems and strategies for optimal programming.
Abstract: The workplace is an important setting for promoting cardiovascular health and cardiovascular disease and stroke prevention in the United States. Well-designed, comprehensive workplace wellness programs have the potential to improve cardiovascular health and to reduce mortality, morbidity, and disability resulting from cardiovascular disease and stroke. Nevertheless, widespread implementation of comprehensive workplace wellness programs is lacking, and program composition and quality vary. Several organizations provide worksite wellness recognition programs; however, there is variation in recognition criteria, and they do not specifically focus on cardiovascular disease and stroke prevention. Although there is limited evidence to suggest that company performance on employer health management scorecards is associated with favorable healthcare cost trends, these data are not currently robust, and further evaluation is needed. As a recognized national leader in evidence-based guidelines, care systems, and quality programs, the American Heart Association/American Stroke Association is uniquely positioned and committed to promoting the adoption of comprehensive workplace wellness programs, as well as improving program quality and workforce health outcomes. As part of its commitment to improve the cardiovascular health of all Americans, the American Heart Association/American Stroke Association will promote science-based best practices for comprehensive workplace wellness programs and establish benchmarks for a national workplace wellness recognition program to assist employers in applying the best systems and strategies for optimal programming. The recognition program will integrate identification of a workplace culture of health and achievement of rigorous standards for cardiovascular health based on Life's Simple 7 metrics. In addition, the American Heart Association/American Stroke Association will develop resources that assist employers in meeting these rigorous standards, facilitating access to high-quality comprehensive workplace wellness programs for both employees and dependents, and fostering innovation and additional research.

77 citations


Journal ArticleDOI
TL;DR: For patients who are unlikely to receive timely pPCI, pretransfer fibrinolysis, followed by early transfer for angiography, may be a reperfusion option when potential benefits of timely reperfusions outweigh bleeding risk.
Abstract: Importance Guidelines for patients with ST-segment elevation myocardial infarction (STEMI) recommend timely reperfusion with primary percutaneous coronary intervention (pPCI) or fibrinolysis. Among patients with STEMI who require interhospital transfer, it is unclear how reperfusion strategy selection and outcomes vary with interhospital drive times. Objective To assess the association of estimated interhospital drive times with reperfusion strategy selection among transferred patients with STEMI in the United States. Design, Setting, and Participants We identified 22 481 patients eligible for pPCI or fibrinolysis who were transferred from 1771 STEMI referring centers to 366 STEMI receiving centers in the Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With the Guidelines database between July 1, 2008, and March 31, 2012. Main Outcomes and Measures In-hospital mortality and major bleeding. Results The median estimated interhospital drive time was 57 minutes (interquartile range [IQR], 36-88 minutes). When the estimated drive time exceeded 30 minutes, only 42.6% of transfer patients treated with pPCI achieved the first door-to-balloon time within 120 minutes. Only 52.7% of eligible patients with a drive time exceeding 60 minutes received fibrinolysis. Among 15 437 patients with estimated drive times of 30 to 120 minutes who were eligible for fibrinolysis or pPCI, 5296 (34.3%) received pretransfer fibrinolysis, with a median door-to-needle time of 34 minutes (IQR, 23-53 minutes). After fibrinolysis, the median time to transfer to the STEMI receiving center was 49 minutes (IQR, 34-69 minutes), and 97.1% underwent follow-up angiography. Patients treated with fibrinolysis vs pPCI had no significant mortality difference (3.7% vs 3.9%; adjusted odds ratio, 1.13; 95% CI, 0.94-1.36) but had higher bleeding risk (10.7% vs 9.5%; adjusted odds ratio, 1.17; 95% CI, 1.02-1.33). Conclusions and Relevance In the United States, neither fibrinolysis nor pPCI is being optimally used to achieve guideline-recommended reperfusion targets. For patients who are unlikely to receive timely pPCI, pretransfer fibrinolysis, followed by early transfer for angiography, may be a reperfusion option when potential benefits of timely reperfusion outweigh bleeding risk.

69 citations


01 Jan 2015
TL;DR: In this article, the efficacy and safety of edoxaban vs. warfarin in patients who were vitamin K antagonist (VKA) naive or experienced were compared in patients with atrial fibrillation.
Abstract: Edoxaban is an oral, once-daily factor Xa inhibitor that is non-inferior to well-managed warfarin in patients with atrial fibrillation (AF) for the prevention of stroke and systemic embolic events (SEEs). We examined the efficacy and safety of edoxaban vs. warfarin in patients who were vitamin K antagonist (VKA) naive or experienced. Methods and results ENGAGE AF-TIMI 48 randomized 21 105 patients with AF at moderate-to-high risk of stroke to once-daily edoxaban vs. warfarin. Subjects were followed for a median of 2.8 years. The primary efficacy endpoint was stroke or SEE. As a pre- specified subgroup, we analysed outcomes for those with or without prior VKA experience (.60 consecutive days). Higher-dose edoxaban significantly reduced the risk of stroke or SEE in patients who were VKA naive (hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.56-0.90) and was similar to warfarin in the VKA experienced (HR 1.01, 95% CI 0.82-1.24; P interaction ¼ 0.028). Lower-dose edoxaban was similar to warfarin for stroke or SEE prevention in patients who were VKA naive (HR 0.92, 95% CI 0.73-1.15), but was inferior to warfarin in those who were VKA experi- enced (HR 1.31, 95% 1.08-1.60; P interaction ¼ 0.019). Both higher-dose and lower-dose edoxaban regimens signifi- cantly reduced the risk of major bleeding regardless of prior VKA experience (P interaction ¼ 0.90 and 0.71, respectively). Conclusion In patients with AF, edoxaban appeared to demonstrate greater efficacy compared with warfarin in patients who were VKA naive than VKA experienced. Edoxaban significantly reduced major bleeding compared with warfarin regardless of prior VKA exposure.

39 citations


Journal ArticleDOI
TL;DR: In patients with AF, edoxaban appeared to demonstrate greater efficacy compared with warfarin in patients who were VKA naive than VKA experienced, and major bleeding was reduced regardless of prior VKA exposure.
Abstract: Aims Edoxaban is an oral, once-daily factor Xa inhibitor that is non-inferior to well-managed warfarin in patients with atrial fibrillation (AF) for the prevention of stroke and systemic embolic events (SEEs). We examined the efficacy and safety of edoxaban vs. warfarin in patients who were vitamin K antagonist (VKA) naive or experienced. Methods and results ENGAGE AF-TIMI 48 randomized 21 105 patients with AF at moderate-to-high risk of stroke to once-daily edoxaban vs. warfarin. Subjects were followed for a median of 2.8 years. The primary efficacy endpoint was stroke or SEE. As a pre-specified subgroup, we analysed outcomes for those with or without prior VKA experience (>60 consecutive days). Higher-dose edoxaban significantly reduced the risk of stroke or SEE in patients who were VKA naive [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.56–0.90] and was similar to warfarin in the VKA experienced (HR 1.01, 95% CI 0.82–1.24; P interaction = 0.028). Lower-dose edoxaban was similar to warfarin for stroke or SEE prevention in patients who were VKA naive (HR 0.92, 95% CI 0.73–1.15), but was inferior to warfarin in those who were VKA experienced (HR 1.31, 95% 1.08–1.60; P interaction = 0.019). Both higher-dose and lower-dose edoxaban regimens significantly reduced the risk of major bleeding regardless of prior VKA experience ( P interaction = 0.90 and 0.71, respectively). Conclusion In patients with AF, edoxaban appeared to demonstrate greater efficacy compared with warfarin in patients who were VKA naive than VKA experienced. Edoxaban significantly reduced major bleeding compared with warfarin regardless of prior VKA exposure.

39 citations


Journal ArticleDOI
TL;DR: A 1.5-day interactive forum was convened to discuss critical issues in the acquisition, analysis, and sharing of data in the field of cardiovascular and stroke science as mentioned in this paper, which will serve as the foundation for the American Heart Association's near-term and future strategies in the Big Data area.
Abstract: Background A 1.5‐day interactive forum was convened to discuss critical issues in the acquisition, analysis, and sharing of data in the field of cardiovascular and stroke science. The discussion will serve as the foundation for the American Heart Association's (AHA's) near‐term and future strategies in the Big Data area. The concepts evolving from this forum may also inform other fields of medicine and science. Methods and Results A total of 47 participants representing stakeholders from 7 domains (patients, basic scientists, clinical investigators, population researchers, clinicians and healthcare system administrators, industry, and regulatory authorities) participated in the conference. Presentation topics included updates on data as viewed from conventional medical and nonmedical sources, building and using Big Data repositories, articulation of the goals of data sharing, and principles of responsible data sharing. Facilitated breakout sessions were conducted to examine what each of the 7 stakeholder domains wants from Big Data under ideal circumstances and the possible roles that the AHA might play in meeting their needs. Important areas that are high priorities for further study regarding Big Data include a description of the methodology of how to acquire and analyze findings, validation of the veracity of discoveries from such research, and integration into investigative and clinical care aspects of future cardiovascular and stroke medicine. Potential roles that the AHA might consider include facilitating a standards discussion (eg, tools, methodology, and appropriate data use), providing education (eg, healthcare providers, patients, investigators), and helping build an interoperable digital ecosystem in cardiovascular and stroke science. Conclusion There was a consensus across stakeholder domains that Big Data holds great promise for revolutionizing the way cardiovascular and stroke research is conducted and clinical care is delivered; however, there is a clear need for the creation of a vision of how to use it to achieve the desired goals. Potential roles for the AHA center around facilitating a discussion of standards, providing education, and helping establish a cardiovascular digital ecosystem. This ecosystem should be interoperable and needs to interface with the rapidly growing digital object environment of the modern‐day healthcare system.

37 citations


Journal Article
TL;DR: There was an apparent decrease in relative efficacy to prevent arterial thromboembolism in the upper range of CrCl, but the safety and net clinical benefit of HDER compared with warfarin are consistent across the range of renal function.
Abstract: Background: Edoxaban (edox), an oral factor Xa inhibitor with 50% renal clearance, was non-inferior to warfarin for prevention of thromboembolic events and significantly reduced bleeding in pts with AF. However, a detailed analysis of the impact of creatinine clearance (CrCl) on clinical outcomes with edox has not been described. Purpose: We evaluated the safety, efficacy and net clinical outcome of edox vs warfarin (warf) across the range of baseline CrCl in the ENGAGE AF-TIMI 48 trial. Methods: 14,071 AF pts at moderate-to-high risk of stroke were randomized to edox 60mg QD or warf. Severe renal dysfunction (CrCl Results: The relative risk of SSE with edox vs warf in the pre-specified analysis in those with CrCl≤50 (HR 0.87, 0.65-1.18) was similar to those with CrCl>50 (HR 0.87, 0.72-1.04; p-int=0.94). Evaluation by more granular, exploratory cutpoints demonstrated higher rates of SSE (Fig 1a; p-int Conclusion: While there is a trend towards decreasing efficacy with increasing CrCl for edox compared to well-managed warfarin, the overall safety and net clinical benefit of edox compared to warfarin is consistent across renal function groups.

Journal ArticleDOI
TL;DR: Despite its higher acquisition cost, edoxaban is an economically attractive alternative to warfarin for the prevention of stroke and SE in patients with atrial fibrillation and creatinine clearance ≤95mL/min.

Journal ArticleDOI
TL;DR: In this paper, the authors performed a prespecified analysis in 21,105 patients with AF enrolled in the ENGAGE AF-TIMI 48 trial, which compared two once-daily regimens of edoxaban with warfarin for the prevention of stroke and systemic embolic events (SEEs).

Journal ArticleDOI
TL;DR: There may be sex differences in response to drug therapies used to treat diabetes, hypertension, and hyperlipidemia in patients with type 2 diabetes and established coronary artery disease enrolled into the BARI 2D trial.
Abstract: Background. Research has shown less aggressive treatment and poorer control of cardiovascular disease (CVD) risk factors in women than men. Methods. We analyzed sex differences in pharmacotherapy strategies and attainment of goals for hemoglobin A1c (HbA1c), blood pressure (BP), and low density lipoprotein cholesterol (LDL-C) in patients with type 2 diabetes and established coronary artery disease enrolled into the BARI 2D trial. Results. Similar numbers of drugs were prescribed in both women and men. Women were less frequent on metformin or sulfonylurea and more likely to take insulin and to be on higher doses of hydroxymethylglutaryl-CoA reductase inhibitors (statins) than men. After adjusting for baseline differences and treatment prescribed, women were less likely to achieve goals for HbA1c (OR = 0.71, 95% CI 0.57, 0.88) and LDL-C (OR = 0.64, 95% CI 0.53, 0.78). More antihypertensives were prescribed to women, and yet BP ≤ 130/80 mmHg did not differ by sex. Conclusions. Women entering the BARI 2D trial were as aggressively treated with drugs as men. Despite equivalent treatment, women less frequently met targets for HbA1c and LDL-C. Our findings suggest that there may be sex differences in response to drug therapies used to treat diabetes, hypertension, and hyperlipidemia.

Journal ArticleDOI
TL;DR: Sidney C. Smith, Jr.
Abstract: Sidney C. Smith, Jr.* Gregg C. Fonarow, Ileana L. Piña, Robert Suter, Louise Morgan,Kathryn Taubert, Eduardo Sanchez, and Elliott Antman Heart and Vascular Center, University of North Carolina, Chapel Hill, North Carolina, United States Division of Cardiology, UCLA David Geffen School of Medicine, Los Angeles, California, United States Division of Cardiology, Albert Einstein College of Medicine, Bronx, New York, United States American Heart Association, Dallas, Texas, United States e Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States

Journal ArticleDOI
TL;DR: The American Heart Association’s clinicians, scientists, lay volunteers, and staff are inspired by your dedication to saving and improving lives and have an unprecedented opportunity to harness these advances to save and improve lives.
Abstract: Good afternoon, and welcome to the Scientific Sessions. On behalf of all of the American Heart Association’s (AHA) clinicians, scientists, lay volunteers, and staff, I extend a warm welcome and offer my thanks for your efforts to understand, prevent, and treat cardiovascular diseases. We are inspired by your dedication to saving and improving lives. The burden of these diseases is something we all share, no matter where we live or work. So let us make the most of our opportunities to learn from one another throughout the Scientific Sessions. For these next 4 days, Chicago is home to the latest in cardiovascular and stroke research. Chicago is also home to significant cardiovascular history. Ninety years ago, Chicago resident Dr James B. Herrick joined Dr Paul Dudley White and 4 other pioneering physicians at Chicago’s Drake Hotel to create the AHA.1 They started this lifesaving organization just 4 miles away from where we are sitting right now. Yet, it was worlds away when we consider what we can offer patients today. We now have tools at our disposal that we could barely imagine only a few years ago. New diagnostic and therapeutic options are being discovered at a pace unseen in human history. We have an unprecedented opportunity to harness these advances to save and improve lives, and that is what I would like to talk to you about. But first, I would like to share a quick illustration of just how much our tools have changed. This 28-pound box is the actual ECG machine Paul Dudley White used in his office decades ago.2 It was considered state of the art back then. With the patient lying supine and connected to the device, a paper recording of the ECG could be obtained, a single lead at a time. Now, …

Journal Article
TL;DR: Patients at increased risk of falling are a high-risk subgroup, with an increased risk for both stroke/SEE as well as for bleeding, and demonstrate consistent efficacy and safety with edoxaban as compared to well-managed warfarin.
Abstract: Background: Patients at an increased risk of falling are particularly at risk for undertreatment with oral anticoagulation The current subgroup analysis assessed the relative efficacy and safety o