Showing papers by "Elliott M. Antman published in 2019"
TL;DR: The ABC-stroke and ABC-bleeding scores evaluated in this anticoagulated clinical trial cohort were well calibrated and outperformed the CHA2DS2-VASc and HAS-BLED scores, respectively, and may help identify patients most likely to derive a benefit from treatment with non–vitamin K antagonist oral antICOagulants.
Abstract: 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 emboli...
91 citations
TL;DR: An increased BMI was independently associated with a lower risk of stroke/SEE, better survival, but increased risk of bleeding, and time in therapeutic range for warfarin improved significantly as BMI increased.
Abstract: 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): underweight ( 18.5 kg/m2, while time in therapeutic range for warfarin improved significantly as BMI increased (P Conclusion An increased BMI was independently associated with a lower risk of stroke/SEE, better survival, but increased risk of bleeding. The efficacy and safety profiles of edoxaban were similar across BMI categories ranging from 18.5 to >40.
82 citations
Durham University1, University of Michigan2, Brigham and Women's Hospital3, University of Washington4, University of Virginia5, American Heart Association6, University of Texas MD Anderson Cancer Center7, Berkshire Medical Center8, Cedars-Sinai Medical Center9, University of California, Los Angeles10, Boston University11
TL;DR: In this paper, the change in treatment strategies and times to treatment over the first 5 years of the Mission: Lifeline program was assessed and the results showed that the change was relatively mild.
Abstract: 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‐hospi...
69 citations
TL;DR: Compared to warfarin, higher dose edoxaban preserved the efficacy for stroke prevention and was associated with a favourable safety profile for Asians, which may be due to the lower trough edxaban concentration and anti-FXa activity achieved in patients of Asian race.
Abstract: 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. Methods and results There were 2909 patients of Asian race and 18 195 non-Asian race in the ENGAGE AF-TIMI 48 trial. The risks of thromboembolism and bleeding events were compared for Asians and non-Asians treated with warfarin. The trough levels of edoxaban concentration and anti-FXa activity were also compared and correlated with the efficacy and safety of edoxaban vs. warfarin. Compared to non-Asian patients, the Asian population was on average 2 years younger and 20 kg lighter. In the warfarin group, the adjusted risk of ischaemic stroke did not differ significantly for patients of Asian and non-Asian race [adjusted hazard ratio (aHR) = 1.12, P = 0.56). Asians treated with warfarin had a higher-adjusted risk of intracranial haemorrhage (ICH: aHR 1.71, P = 0.03) compared with non-Asians. The trough edoxaban concentration and anti-FXa activity were 20-25% lower for Asians compared with non-Asians. Compared to warfarin, higher dose edoxaban significantly reduced ICH while preserving the efficacy of stroke prevention in both Asians and non-Asians. Two of three net clinical outcomes appeared to be more favourably reduced with edoxaban in Asians compared with non-Asians (Pint = 0.063 for primary, 0.037 for secondary, and 0.032 for third net clinical outcomes, respectively). Conclusion Compared to warfarin, higher dose edoxaban preserved the efficacy for stroke prevention and was associated with a favourable safety profile for Asians, which may be due to the lower trough edoxaban concentration and anti-FXa activity achieved in patients of Asian race.
54 citations
TL;DR: After accounting for cardiovascular risk factors, women enrolled in clinical trials were at lower risk of MACE than men after NSTEACS, however, women remain undertreated with many evidence-based therapies.
48 citations
TL;DR: The present study aimed to assess the association between left atrial (LA) structure and function and the risk for cardiovascular death or heart failure hospitalization in a population with atrial fibrillation.
Abstract: 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 Next Generation in AF-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) study, 971 patients underwent transthoracic echocardiography. The associations between LA structure (LA volume index [LAVi]) and function (LA emptying fraction [LAEF] and LA expansion index [LAEi]) and risk for the composite endpoint of CV death or HF hospitalization, and its components, were assessed. Over a median follow-up of 2.5 years, 142 patients (14.6%) experienced CV death or HF hospitalization. Higher LAVi and lower LAEF and LAEi were each associated with a higher unadjusted risk for the composite outcome and its components. After adjustment for clinical and echocardiographic confounders, only measures of impaired LA function were predictive of the composite outcome (hazard ratio [HR] per 1 standard deviation [SD] decrease in LAEF: 1.35; 95% confidence interval [CI] 1.09-1.67 [P = 0.005]; HR per 1 SD decrease in LAEi: 1.34; 95% CI 1.06-1.69 [P = 0.012]). These findings were similar regardless of left ventricular ejection fraction, history of HF or whether patients were in AF or sinus rhythm at the time of the echocardiographic examination. Conclusions In patients with AF, LA dysfunction was significantly associated with an increased risk for CV death or HF hospitalization and was more predictive of these outcomes than LA size. These parameters may help to identify AF patients at greatest risk for the development of HF. Clinical trial registration ClinicalTrials.gov, NCT00781391.
37 citations
TL;DR: Among patients with AF receiving oral anticoagulation, bleeding, but not thromboembolic events, was increased in patients with liver disease, and a history of liver disease did not alter the relative efficacy and safety of edoxaban compared with warfarin.
32 citations
TL;DR: The reduction in ischemic events with the higher-dose edoxaban regimen versus warfarin was greater in patients with CAD, while bleeding was significantly reduced with edoxaba regardless of CAD status.
Abstract: 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...
17 citations
TL;DR: There was an approximately four-fold difference in the frequency of the most severe bleeding events across commonly used bleeding scales among patients with AF at risk for stroke, and the relative safety of edoxaban as compared with warfarin tended to increase with greater severity of bleeding.
Abstract: 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...
17 citations
TL;DR: The present meta-analysis of four trials supports that NOACs are safe and at least as effective as warfarin in patients with atrial fibrillation and established CAD.
Abstract: 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 a...
13 citations
TL;DR: The efficacy and safety of Edoxaban were consistent across the full range of SBP, while the superior safety of edoxaban was most pronounced among patients with elevated DBP, which is a risk factor for stroke and bleeding in patients with atrial fibrillation.
Abstract: 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 dire...
TL;DR: Genetic profiling using FADS2 genotype can predict the therapeutic benefits of O-3FA treatment against adverse cardiac remodeling during the convalescent phase of AMI.
Abstract: 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 and omega-6 fatty acids into active arachidonic (ArA) and eicosapentaenoic acids (EPA), which influence cardiovascular outcomes. Methods and results We tested the hypothesis that the genotypic status of FADS2 (rs1535) modifies therapeutic response of O-3FA in post-AMI cardiac remodeling in 312 patients. Consistent with known genetic polymorphism of FADS2, patients in our cohort with the guanine-guanine (GG) genotype had the lowest FADS2 activity assessed by arachidonic acid/linoleic acid (ArA/LA) ratio, compared with patients with the adenine-adenine (AA) and adenine-guanine (AG) genotypes (GG:1.62±0.35 vs. AA: 2.01±0.36, p<0.0001; vs. AG: 1.76±0.35, p = 0.03). When randomized to 6-months of O-3FA treatment, GG patients demonstrated significant lowering of LV end-systolic volume index (LVESVi), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and galectin-3 levels compared to placebo (-4.4 vs. 1.2 ml/m2, -733 vs. -181 pg/mL, and -2.0 vs. 0.5 ng/mL; p = 0.006, 0.006, and 0.03, respectively). In contrast, patients with either AA or AG genotype did not demonstrate significant lowering of LVESVi, NT-proBNP, or galectin-3 levels from O-3FA treatment, compared to placebo. The odds ratios for improving LVESVi by 10% with O-3FA treatment was 7.2, 1.6, and 1.2 in patients with GG, AG, and AA genotypes, respectively. Conclusion Genetic profiling using FADS2 genotype can predict the therapeutic benefits of O-3FA treatment against adverse cardiac remodeling during the convalescent phase of AMI. Clinical trial registration information clinicaltrials.gov Identifier: NCT00729430.
01 Jul 2019
TL;DR: This study highlights the need to understand more fully the rationale behind the continued use of these devices, as well as the barriers to adoption and their potential in the coming years.
Abstract: Richard E. Kuntz, MD, Medtronic, Inc.; Elliott M. Antman, MD, FAHA, MACC, Harvard Medical School; Robert M. Califf , MD, MACC, Duke University; Julie R. Ingelfi nger, MD, Harvard Medical School; Harlan M. Krumholz, MD, SM, Yale School of Medicine; Alexander Ommaya, DSc, Association of American Medical Colleges; Eric D. Peterson, MD, MPH, FAHA, FACC, Duke Clinical Research Institute; Joseph S. Ross, MD, MHS, Yale University School of Medicine; Joanne Waldstreicher, MD, Johnson & Johnson; Shirley V. Wang, PhD, MSc, Harvard Medical School; Deborah A. Zarin, MD, Harvard Medical School; Danielle M. Whicher, PhD, MHS, National Academy of Medicine; Sameer M. Siddiqi, PhD, National Academy of Medicine; and Marianne Hamilton Lopez, PhD, MPA, DukeMargolis Center for Health Policy
TL;DR: In this first experience of patients undergoing device surgery with edoxaban, a low risk of ischaemic and bleeding events was observed during the first 30 days post-procedure.
Abstract: 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. Methods and results During the trial, 1217 device procedures were performed in 1145 patients, with intervention dates available for 1203 procedures. Two hundred and twenty-five procedures (in 212 patients) were performed >30 days after study drug was stopped and are not included in the event analysis. For most interventions (n = 728, 74%), study drug was interrupted >3 days (median for the entire cohort: 5 days, interquartile range 0-11 days); 250 interventions were performed with ≤3 days study drug interruption. During the first 30 days after the procedure, six strokes/systemic embolic events (SEEs) (three each in the lower-dose edoxaban and warfarin arm) and one major bleeding event (in the lower-dose edoxaban arm) occurred; no stroke/SEEs or major bleeds occurred around the 295 device procedures in the higher-dose edoxaban arm. Two ischaemic and one major bleeding event occurred after the 288 device procedures performed with ≤3 days periprocedural interruption of study drug. Conclusion In this first experience of patients undergoing device surgery with edoxaban, a low risk of ischaemic and bleeding events was observed during the first 30 days post-procedure. Our data are in line with current recommendations of no or only brief interruption of non-vitamin K antagonist oral anticoagulants prior to cardiac device surgery.
TL;DR: Additional data in patients with more advanced liver disease and in larger groups of unselected patients are needed to supplement the data from the ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation).