Showing papers by "Elliott M. Antman published in 2016"
TL;DR: In this article, an oral factor Xa inhibitor with 50% renal clearance was compared to well-managed warfarin for stroke or systemic embolism prevention and reduced bleeding in patient.
Abstract: Background:Edoxaban, an oral factor Xa inhibitor with 50% renal clearance, was noninferior to well-managed warfarin for stroke or systemic embolism (S/SE) prevention and reduced bleeding in patient...
215 citations
TL;DR: Age has a greater influence on major bleeding than thromboembolic risk in patients with atrial fibrillation, and treatment of elderly patients with edoxaban provides an even greater absolute reduction in safety events over warfarin, compared to treatment with Edoxaban versus warFarin in younger patients.
Abstract: Background Elderly patients with atrial fibrillation are at higher risk of both ischemic and bleeding events compared to younger patients. In a prespecified analysis from the ENGAGE AF‐TIMI 48 trial, we evaluate clinical outcomes with edoxaban versus warfarin according to age.
Methods and Results Twenty‐one thousand one‐hundred and five patients enrolled in the ENGAGE AF‐TIMI 48 trial were stratified into 3 prespecified age groups: <65 (n=5497), 65 to 74 (n=7134), and ≥75 (n=8474) years. Older patients were more likely to be female, with lower body weight and reduced creatinine clearance, leading to higher rates of edoxaban dose reduction (10%, 18%, and 41% for the 3 age groups, P <0.001). Stroke or systemic embolic event (1.1%, 1.8%, and 2.3%) and major bleeding (1.8%, 3.3%, and 4.8%) rates with warfarin increased across age groups ( P trend<0.001 for both). There were no interactions between age group and randomized treatment in the primary efficacy and safety outcomes. In the elderly (≥75 years), the rates of stroke/systemic embolic event were similar with edoxaban versus warfarin (hazard ratio 0.83 [0.66–1.04]), while major bleeding was significantly reduced with edoxaban (hazard ratio 0.83 [0.70–0.99]). The absolute risk difference in major bleeding (−82 events/10 000 pt‐yrs) and in intracranial hemorrhage (−73 events/10 000 pt‐yrs) both favored edoxaban over warfarin in older patients.
Conclusions Age has a greater influence on major bleeding than thromboembolic risk in patients with atrial fibrillation. Given the higher rates of bleeding and death with increasing age, treatment of elderly patients with edoxaban provides an even greater absolute reduction in safety events over warfarin, compared to treatment with edoxaban versus warfarin in younger patients.
Clinical Trial Registration URL: . Unique identifier: NCT00781391.
206 citations
TL;DR: The cardiovascular research and clinical communities are ideally positioned to address the epidemic of noncommunicable causes of death, as well as advance the understanding of human health and disease, through the development and implementation of precision medicine.
Abstract: The cardiovascular research and clinical communities are ideally positioned to address the epidemic of noncommunicable causes of death, as well as advance our understanding of human health and disease, through the development and implementation of precision medicine. New tools will be needed for describing the cardiovascular health status of individuals and populations, including 'omic' data, exposome and social determinants of health, the microbiome, behaviours and motivations, patient-generated data, and the array of data in electronic medical records. Cardiovascular specialists can build on their experience and use precision medicine to facilitate discovery science and improve the efficiency of clinical research, with the goal of providing more precise information to improve the health of individuals and populations. Overcoming the barriers to implementing precision medicine will require addressing a range of technical and sociopolitical issues. Health care under precision medicine will become a more integrated, dynamic system, in which patients are no longer a passive entity on whom measurements are made, but instead are central stakeholders who contribute data and participate actively in shared decision-making. Many traditionally defined diseases have common mechanisms; therefore, elimination of a siloed approach to medicine will ultimately pave the path to the creation of a universal precision medicine environment.
163 citations
TL;DR: Treatment of patients with acute myocardial infarction with high-dose omega-3 fatty acids was associated with reduction of adverse left ventricular remodeling, noninfarctMyocardial fibrosis, and serum biomarkers of systemic inflammation beyond current guideline-based standard of care.
Abstract: Background:Omega-3 fatty acids from fish oil have been associated with beneficial cardiovascular effects, but their role in modifying cardiac structures and tissue characteristics in patients who have had an acute myocardial infarction while receiving current guideline-based therapy remains unknown. Methods:In a multicenter, double-blind, placebo-controlled trial, participants presenting with an acute myocardial infarction were randomly assigned 1:1 to 6 months of high-dose omega-3 fatty acids (n=180) or placebo (n=178). Cardiac magnetic resonance imaging was used to assess cardiac structure and tissue characteristics at baseline and after study therapy. The primary study endpoint was change in left ventricular systolic volume index. Secondary endpoints included change in noninfarct myocardial fibrosis, left ventricular ejection fraction, and infarct size. Results:By intention-to-treat analysis, patients randomly assigned to omega-3 fatty acids experienced a significant reduction of left ventricular systo...
135 citations
TL;DR: Edoxaban is an attractive alternative to warfarin in patients at increased risk of falling, because it is associated with an even greater absolute reduction in severe bleeding events and mortality.
132 citations
TL;DR: Patients with AF who were selected by their physicians to receive SAPT in addition to an anticoagulant had a similar risk of stroke/SEE and higher rates of bleeding than those not receiving SAPT and Edoxaban exhibited similar relative efficacy and reduced bleeding compared to warfarin, with or without concomitant SAPT.
Abstract: Background We studied the concomitant use of single antiplatelet therapy (SAPT) on the efficacy and safety of the anti‐Xa agent edoxaban in patients with atrial fibrillation (AF).
Methods and Results ENGAGE AF‐TIMI 48 was a randomized trial that compared 2 dose regimens of edoxaban with warfarin. We studied both the approved high‐dose edoxaban regimen (HDER; 60 mg daily reduced by one half in patients with anticipated increased drug exposure), as well as a lower‐dose edoxaban regimen (LDER; 30 mg daily, also reduced by one half in patients with anticipated increased drug regimen). SAPT (aspirin in 92.5%) was administered at the discretion of the treating physician. Cox proportional hazard regressions stratified by SAPT at 3 months with treatment as a covariate were performed. The 4912 patients who received SAPT were more frequently male, with histories of coronary artery disease and diabetes, and had higher CHADS2Vasc and HAS BLED scores than did the 14 977 patients not receiving SAPT. When compared to patients not receiving SAPT, those receiving SAPT had a higher incidence of major bleeding; (adjusted hazard ratio [HRadj]=1.46; 95% CI, 1.27–1.67, P <0.001). SAPT did not alter the relative efficacy of edoxaban compared to warfarin in preventing stroke or systemic embolic events (SEEs): edoxaban versus warfarin without SAPT, hazard ratio (HRadj for HDER)=0.94; (95% CI: 0.77–1.15) with SAPT, HRadj=0.70 (95% CI: 0.50–0.98), P interaction ( P int)=0.14. (HRadj for LDER versus warfarin without SAPT=1.19 (95% CI 0.99–1.43) With SAPT, 1.03 (95% CI, 0.76–1.39) P int=0.42. Major bleeding was lower with edoxaban than warfarin both without SAPT, HRadj for HDER=0.80 (95% CI, 0.68–0.95), and with SAPT, HRadj=0.82 (95% CI, 0.65–1.03; P int=0.91). For LDER without SAPT (HRadj=0.56 [95% CI 0.46–0.67]) and with SAPT (HRadj=0.51 [95% CI 0.39–0.66]).
Conclusions Patients with AF who were selected by their physicians to receive SAPT in addition to an anticoagulant had a similar risk of stroke/SEE and higher rates of bleeding than those not receiving SAPT. Edoxaban exhibited similar relative efficacy and reduced bleeding compared to warfarin, with or without concomitant SAPT.
Clinical Trial Registration URL: . Unique identifier: NCT00781391.
95 citations
TL;DR: Despite similar or lower rates of serious bleeding with NOACs in comparison with warfarin, there is a pressing need for strategies to manage bleeding when it does occur and to reverse the pharmacological effect of these agents if needed.
Abstract: Vitamin K antagonists are commonly used by clinicians to provide anticoagulation to patients who have or are at risk of having thrombotic events. In addition to familiarity with the dosing and monitoring of vitamin K antagonists, clinicians are accustomed to using vitamin K if there is a need to reverse the anticoagulant effect of vitamin K antagonists. There are now 4 new non-vitamin K antagonist oral anticoagulants (NOACs) that are attractive alternatives to vitamin K antagonists. Despite similar or lower rates of serious bleeding with NOACs in comparison with warfarin, there is a pressing need for strategies to manage bleeding when it does occur with NOACs and to reverse the pharmacological effect of these agents if needed. Important steps in minimizing bleeding risks with NOACs include dose adjustment of the agents in the setting of renal dysfunction and avoidance of the concomitant use of other antithrombotic agents if feasible. Laboratory measurement of the anticoagulant effect of NOACs is best accomplished with specialized assays, although some of the more widely available coagulation tests can provide information that is potentially useful to clinicians. Nonspecific hemostatic agents such as prothrombin complex concentrates and recombinant factor VIIa can be used to reverse the effect of NOACs. More specific reversing agents include the approved humanized monoclonal antibody fragment idarucizumab for reversing the effects of dabigatran, the investigational factor Xa decoy andexanet alfa, and the synthetic small molecule ciraparantag. Both andexanet and ciraparantag have been reported to reverse the effects of the anti-Xa NOACs (rivaroxaban, apixaban, and edoxaban), and a number of other anticoagulant agents in common clinical use, as well.
91 citations
TL;DR: HDER is at least as effective and is safer than warfarin, regardless of the presence or the absence of previous IS or TIA, and annualized intracranial hemorrhage rates were lower with HDER than with warfar in this prespecified subgroup analysis.
Abstract: Background and Purpose— Patients with atrial fibrillation and previous ischemic stroke (IS)/transient ischemic attack (TIA) are at high risk of recurrent cerebrovascular events despite anticoagulation. In this prespecified subgroup analysis, we compared warfarin with edoxaban in patients with versus without previous IS/TIA.
Methods— ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) was a double-blind trial of 21 105 patients with atrial fibrillation randomized to warfarin (international normalized ratio, 2.0–3.0; median time-in-therapeutic range, 68.4%) versus once-daily edoxaban (higher-dose edoxaban regimen [HDER], 60/30 mg; lower-dose edoxaban regimen, 30/15 mg) with 2.8-year median follow-up. Primary end points included all stroke/systemic embolic events (efficacy) and major bleeding (safety). Because only HDER is approved, we focused on the comparison of HDER versus warfarin.
Results— Of 5973 (28.3%) patients with previous IS/TIA, 67% had CHADS2 (congestive heart failure, hypertension, age, diabetes, prior stroke/transient ischemic attack) >3 and 36% were ≥75 years. Compared with 15 132 without previous IS/TIA, patients with previous IS/TIA were at higher risk of both thromboembolism and bleeding (stroke/systemic embolic events 2.83% versus 1.42% per year; P <0.001; major bleeding 3.03% versus 2.64% per year; P <0.001; intracranial hemorrhage, 0.70% versus 0.40% per year; P <0.001). Among patients with previous IS/TIA, annualized intracranial hemorrhage rates were lower with HDER than with warfarin (0.62% versus 1.09%; absolute risk difference, 47 [8–85] per 10 000 patient-years; hazard ratio, 0.57; 95% confidence interval, 0.36–0.92; P =0.02). No treatment subgroup interactions were found for primary efficacy ( P =0.86) or for intracranial hemorrhage ( P =0.28).
Conclusions— Patients with atrial fibrillation with previous IS/TIA are at high risk of recurrent thromboembolism and bleeding. HDER is at least as effective and is safer than warfarin, regardless of the presence or the absence of previous IS or TIA.
Clinical Trial Registration— URL: . Unique identifier: [NCT00781391][1].
[1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00781391&atom=%2Fstrokeaha%2F47%2F8%2F2075.atom
81 citations
TL;DR: The current landscape of cardiovascular clinical trials in the United States is examined, recently conducted registry-based clinical trials are highlighted, and the potential attributes of the recently launched pragmatic clinical trial called the ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing the Benefits and Long-term Effectiveness) trial are discussed.
71 citations
TL;DR: In the ENGAGE AF-TIMI 48 trial, edoxaban was not found to be inferior to warfarin for the prevention of stroke or systemic embolic events (SEE) in patients with atrial fibrillation (AF) and was associated with significantly less bleeding.
Abstract: Aims
In the ENGAGE AF-TIMI 48 trial, edoxaban, a factor Xa inhibitor, was not found to be inferior to warfarin for the prevention of stroke or systemic embolic events (SEE) in patients with atrial fibrillation (AF) and was associated with significantly less bleeding. The higher-dose edoxaban regimen (HDER; 60 mg dose-reduced to 30 mg once daily) has been approved in various countries in Europe, the USA, and Japan. Among patients treated with vitamin K antagonists (VKAs), symptomatic heart failure (HF) is an independent risk factor for lower time-in-therapeutic range, which reduces the efficacy and safety of VKA therapy. We evaluated the efficacy and safety of edoxaban compared with warfarin across the spectrum of HF severity in the ENGAGE AF-TIMI 48 trial.
Methods and results
Of 14 071 patients randomized to well-controlled warfarin or the HDER, 5926 (42%) had no history of HF, 6344 (45%) were in New York Heart Association (NYHA) class I–II, and 1801 (13%) were in NYHA class III–IV. The efficacy of edoxaban compared with warfarin in preventing stroke/SEE was similar in patients without and with HF regardless of the severity of HF; [HDER vs. warfarin: No-HF: hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.69–1.11; NYHA class I–II: HR 0.88, 95% CI 0.69–1.12; NYHA class III–IV: HR 0.83, 95% CI 0.55–1.25; Pinteraction = 0.97]. Compared with warfarin, HDER was consistently associated with lower risk of major bleeding (No-HF: HR 0.82, 95% CI 0.68–0.99; NYHA class I–II: HR 0.79, 95% CI 0.65–0.96; NYHA class III–IV: HR 0.79, 95% CI 0.54–1.17; Pinteraction = 0.96).
Conclusion
The relative efficacy and safety of HDER compared with well-managed warfarin in AF patients with HF were similar to those without HF.
69 citations
TL;DR: A prototype multimarker risk score was developed to determine the probability of stroke, systemic embolic events, or death by assigning tiered points for higher concentrations of the biomarkers to improve prognostic accuracy in patients with atrial fibrillation.
Abstract: Importance Treatment decisions in atrial fibrillation (AF) are based on clinical assessment of risk. The CHA 2 DS 2 -VASc (cardiac failure or dysfunction, hypertension, age 65-74 [1 point] or ≥75 years [2 points], diabetes mellitus, and stroke, transient ischemic attack or thromboembolism [2 points]–vascular disease, and sex category [female]) risk score is pragmatic and widely used but has only moderate discrimination. Objective To develop and test a cardiovascular biomarker score for indication of risk in patients with AF. Design, Setting, and Participants The ENGAGE AF-TIMI 48 trial was a randomized, double-blind, double-dummy clinical trial comparing 2 once-daily edoxaban dose regimens with warfarin in 21 105 patients with AF at moderate to high risk of stroke. This prespecified subanalysis was performed in 4880 patients enrolled at randomization in the biomarker substudy. Cardiac troponin I, N-terminal pro-B-type natriuretic peptide, andd-dimer levels were measured at baseline. A multimarker risk score was developed to determine the probability of stroke, systemic embolic events, or death by assigning tiered points for higher concentrations of the biomarkers. Main Outcomes and Measures Risk score and clinical outcomes based on cardiac troponin I, N-terminal pro-B-type natriuretic peptide, andd-dimer levels at baseline. Results Of the 5002 patients enrolled in the biomarker substudy of the ENGAGE AF-TIMI 48 trial, 4880 patients (97.6%) had all 3 biomarkers available at randomization (1820 [37.3%] were women; median [interquartile range] age, 71 [64-77] years). After adjustment for the CHA 2 DS 2 -VASc score, each biomarker was associated with a 2.8-fold to 4.2-fold gradient of risk comparing the highest vs lowest concentrations across groups of increasing concentrations ( P 2 DS 2 -VASc score. When added to the CHA 2 DS 2 -VASc score, the biomarker score significantly enhanced prognostic accuracy by improving the C statistic from 0.586 (95% CI, 0.565-0.607) to 0.708 (95% CI, 0.688-0.728) ( P P Conclusions and Relevance A prototype multimarker risk score significantly enhanced risk assessment for stroke, systemic embolic events, or death compared with traditional clinical risk stratification. Incorporation of biomarkers into clinical decision making to define therapeutic management in AF warrants consideration. Trial Registration clinicaltrials.gov Identifier:NCT00781391
TL;DR: SCD is the most common cause of cardiovascular death in patients with atrial fibrillation and has several distinct predictors, some of which are modifiable, which may be considered in planning research and treatment strategies for patients withAtrial Fibrillation.
Abstract: Background Recent findings suggest that atrial fibrillation is associated with sudden cardiac death (SCD). We examined the incidence, characteristics, and factors associated with SCD in patients with atrial fibrillation.
Methods and Results SCD was defined as witnessed death ≤60 minutes from the onset of new symptoms or unwitnessed death 1 to 24 hours after being observed alive, without another known cause of death. Predictors of SCD were examined using multivariate competing risks models. Over 2.8 years (median), 2349 patients died (40.5 per 1000 patient‐years), of which 1668 (71%) were cardiovascular deaths. SCD was the most common cause of cardiovascular death (n=749; median age 73 years; 70.6% male). Most SCD events occurred out of hospital (92.8%) and without prior symptoms (66.0%). Predictors of SCD included low ejection fraction, heart failure, and prior myocardial infarction ( P <0.001 for each). Additional significant baseline predictors of SCD, but not of other causes of death, included male sex, electrocardiographic left ventricular hypertrophy, higher heart rate, nonuse of beta blockers, and use of digitalis. The latter was associated with SCD in patients with or without heart failure (adjusted hazard ratio 1.55 [95% CI 1.29–1.86] and 1.56 [95% CI 1.14–2.11], respectively; P interaction=0.73). The rate of SCD was numerically but not statistically lower with edoxaban (1.20% per year with lower dose edoxaban; 1.28% per year with higher dose edoxaban) compared with warfarin (1.40% per year).
Conclusion SCD is the most common cause of cardiovascular death in patients with atrial fibrillation and has several distinct predictors, some of which are modifiable. These findings may be considered in planning research and treatment strategies for patients with atrial fibrillation.
Clinical Trial Registration URL: . Unique identifier: NCT00781391.
TL;DR: Fewer total and cardiovascular deaths were observed with edoxaban as compared with warfarin in the ENGAGE AF-TIMI 48 trial, and this predominantly resulted from the significantly lower rate of major bleeding with Edoxaban.
TL;DR: In clopidogrel-treated patients in TRITON-TIMI 38, there was no association between Q192R and the rates of CV death, myocardial infarction, or stroke, and a meta-analysis reinforced a lack of a significant association betweenQ192R
Abstract: Clopidogrel and prasugrel are antiplatelet therapies commonly used to treat patients with cardiovascular disease. They are both pro-drugs requiring biotransformation into active metabolites. It has been proposed that a genetic variant Q192R (rs662 A>G) in PON1 significantly alters the biotransformation of clopidogrel and affects clinical outcomes; however, this assertion has limited support. The relationship between this variant and clinical outcomes with prasugrel has not been studied. We genotyped PON1 Q192R in 275 healthy subjects treated with clopidogrel or prasugrel and 2922 patients with an ACS undergoing PCI randomized to treatment with clopidogrel or prasugrel in the TRITON-TIMI 38 trial. A meta-analysis was performed including 13 studies and 16,760 clopidogrel-treated patients. Among clopidogrel-treated subjects, there were no associations between Q192R and active drug metabolite levels (P = 0.62) or change in platelet aggregation (P = 0.51). Consistent with these results, in clopidogrel-treated patients in TRITON-TIMI 38, there was no association between Q192R and the rates of CV death, myocardial infarction, or stroke (RR 11.2 %, QR 8.6 %, and QQ 9.3 %; P = 0.66) or stent thrombosis (RR 2.4 %, QR 0.7 %, and QQ 1.6 %, P = 0.30), with patients with the putative at-risk Q variant having numerically lower event rates. Likewise, among prasugrel-treated subjects, there were no associations between Q192R and active drug metabolite levels (P = 0.88), change in platelet aggregation (P = 0.97), or clinical outcomes (P = 0.72). In a meta-analysis, the Q variant was not significantly associated with MACE (QQ vs. RR 1.22, 95 % CI 0.84-1.76) or stent thrombosis (QQ vs. RR OR 1.36, 95 % CI 0.77-2.38). Furthermore, when restricted to the validation studies, the OR (95 % CI) for MACE and stent thrombosis were 0.99 (0.77-1.27) and 1.23 (0.74-2.03), respectively. In the present study, the Q192R genetic variant in PON1 was not associated with the pharmacologic or clinical response to clopidogrel, nor was it associated with the response to prasugrel. The meta-analysis reinforced a lack of a significant association between Q192R and cardiovascular outcomes in clopidogrel-treated patients.
TL;DR: AHA public policy advocacy strategies are based on its Strategic Impact Goals as discussed by the authors, and the evidence behind AHA's policies to determine how well they address the association's 2020 cardiovascular health (CVH) metrics and cardiovascular disease (CVD) management indicators and identified research needed to fill gaps in policy and support further policy development.
Abstract: Background—American Heart Association (AHA) public policy advocacy strategies are based on its Strategic Impact Goals. The writing group appraised the evidence behind AHA’s policies to determine how well they address the association’s 2020 cardiovascular health (CVH) metrics and cardiovascular disease (CVD) management indicators and identified research needed to fill gaps in policy and support further policy development. Methods and Results—The AHA policy research department first identified current AHA policies specific to each CVH metric and CVD management indicator and the evidence underlying each policy. Writing group members then reviewed each policy and the related metrics and indicators. The results of each review were summarized, and topic-specific priorities and overarching themes for future policy research were proposed. There was generally close alignment between current AHA policies and the 2020 CVH metrics and CVD management indicators; however, certain specific policies still lack a robust e...
TL;DR: In a contemporary population of patients with AF at increased risk for thromboembolic events, larger LV size and higher filling pressures were significantly associated with increased risk of death, but neither left atrial nor LV measures were associated with thrombuembolic risk.
Abstract: Background Atrial fibrillation (AF) is associated with increased risk for thromboembolism and death; however, the relationships between cardiac structure and function and adverse outcomes among individuals with AF are incompletely understood. Methods The Effective Anticoagulation with Factor Xa Next Generation in AF–Thrombolysis in Myocardial Infarction 48 study tested the once-daily oral factor Xa inhibitor edoxaban in comparison with warfarin for the prevention of stroke (ischemic or hemorrhagic) or systemic embolism in 21,105 subjects with nonvalvular AF and increased risk for thromboembolic events (CHADS 2 score ≥ 2). In a prospective substudy of 971 subjects who underwent transthoracic echocardiography at baseline, Cox proportional hazards models were used to evaluate associations between cardiac structure and function and the risks for death and thromboembolism (ischemic stroke, transient ischemic attack, or systemic embolism). Results Over a median follow-up period of 2.5 years, 89 deaths (9.2%) and 48 incident thromboembolic events (4.9%) occurred in 971 subjects. In models adjusted for CHADS 2 score, aspirin use, and randomized treatment, larger left ventricular (LV) end-diastolic volume index (hazard ratio per 1 SD [12.9 mL/m 2 ], 1.49; 95% CI, 1.16–1.91) and higher LV filling pressures measured by E/e′ ratio (hazard ratio per 1 SD [4.6], 1.32; 95% CI, 1.08–1.61) were independently associated with increased risks for death. E/e′ ratio > 13 significantly improved the prediction of death beyond clinical factors alone. No features of cardiac structure and function were independently associated with thromboembolism in this population. Findings were similar when adjusted for CHA 2 DS 2 -VASc score in place of CHADS 2 score. Conclusions In a contemporary population of patients with AF at increased risk for thromboembolic events, larger LV size and higher filling pressures were significantly associated with increased risk for death, but neither left atrial nor LV measures were associated with thromboembolic risk. LV size and filling pressures may help identify patients with AF at increased risk for death.
TL;DR: Treatment with edoxaban 60/30 mg was superior to warfarin in the prevention of SSE and significantly reduced cardiovascular death and bleeding, especially fatal bleeding and hemorrhagic stroke.
TL;DR: The ESC 2016 Guideline on the Diagnosis of heart failure as mentioned in this paper has been published in collaboration with the American College of Cardiology (ACC), the American Heart Association (AHA), and the European Society ofCardiology (ESC).
Abstract: The American College of Cardiology (ACC), the American Heart Association (AHA), and the European Society of Cardiology (ESC) are pleased to announce the publication of 2 updated clinical practice guidelines on management of patients with heart failure, which have been produced in collaboration with the Heart Failure Society of America (HFSA) and the Heart Failure Association (HFA) of the ESC.
The introduction of an angiotensin receptor-neprilysin inhibitor (ARNI), valsartan/sacubitril, and a sinoatrial node modulator, ivabradine, when applied judiciously, complement established pharmacological and device-based therapies, representing milestones in the evolution of care for patients with heart failure. Accordingly, the writing committees of the “ESC 2016 Guideline on the Diagnosis …
TL;DR: Interface of the continuum of clinical research and research standards shows the spectrum of trials where research subjects are randomized to medical interventions and followed prospectively, and the core principles of human investigation apply across the spectrum, but the focus of the research standards varies.
Abstract: Approximately 70 years ago, the concept of randomization of individual participants in clinical trials was first introduced, along with informed consent, the ethics of randomized, controlled trials (RCTs), and blinding of treatment assignment.1 A decade later Kaplan and Meier described a mathematical approach to estimating event-free survival at any time T , allowing comparison of the response to treatments over time.2 Building on this strong foundation, clinical investigators began performing a rich array of RCTs that attempted to answer the question of whether a medical intervention was effective, under the ideal circumstances of a circumscribed population and defined treatment protocol (Figure). Blinded RCTs are useful for evaluating investigational products and are central to the development pathway of new medical products. The efficacy and safety data generated in an RCT provide regulatory authorities with the information they need to judge whether a product can be approved for use in clinical practice.
Figure.
Interface of the continuum of clinical research and research standards. On the left is shown the spectrum of trials where research subjects are randomized to medical interventions and followed prospectively. These range from those conducted under ideal circumstances to those conducted under usual conditions of clinical care. A mapping tool is shown where investigators use a Likert scale to score a trial design along nine domains as to whether it is predominantly explanatory (score=1) or pragmatic (score=5). The typical purpose of the trial type and the ethics and focus of research standards are shown at the bottom left. The core principles of human investigation apply across the spectrum, but the focus of the research standards varies. Big Data analyses incorporate inputs (not shown) of previously acquired data into a predictive analytic system and generate recommendations for more precise care of individuals and populations. Depending on the type of …
TL;DR: The introduction of an angiotensin receptor-neprilysin inhibitor (ARNI), valsartan/sacubitril, and a sinoatrial node modulator, ivabradine, when applied judiciously, complement established pharmacological and device-based therapies, representing milestones in the evolution of care for patients with heart failure.
Abstract: The American College of Cardiology (ACC), the American Heart Association (AHA), and the European Society of Cardiology (ESC) are pleased to announce the publication of 2 updated clinical practice guidelines on management of patients with heart failure, which have been produced in collaboration with the Heart Failure Society of America (HFSA) and the Heart Failure Association (HFA) of the ESC.
The introduction of an angiotensin receptor-neprilysin inhibitor (ARNI), valsartan/sacubitril, and a sinoatrial node modulator, ivabradine, when applied judiciously, complement established pharmacological and device-based therapies, representing milestones in the evolution of care for patients with heart failure. Accordingly, the writing committees of the “ESC 2016 Guideline on the Diagnosis …
01 Jan 2016
TL;DR: Sidney C. Smith, Jr., Gregg C. Fonarow, Ileana L. Pina, Robert Suter, Louise Morgan, Kathryn Taubert, Eduardo Sanchez, and Elliott Antman Heart and Vascular Center as mentioned in this paper.
Abstract: Sidney C. Smith, Jr.* Gregg C. Fonarow, Ileana L. Pina, 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
TL;DR: This editorial refers to ‘2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure’, by P. Ponikowski et al, on page 2129.
Abstract: [ This editorial refers to ‘2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure’[†][2], by P. Ponikowski et al ., on page 2129. ][2]
The American College of Cardiology (ACC), the American Heart Association (AHA), and the European Society of Cardiology (ESC)
Journal Article•
TL;DR: Outcomes by DM status and randomized anticoagulant in a large AF trial assessed for effect modification byDM status on the relative efficacy and safety of edoxaban vs warfarin and the primary endpoints were stroke/SEE and ISTH major bleeding.
Abstract: Introduction: AF is twice as prevalent in patients with diabetes mellitus (DM) and DM is associated with increased risk of stroke, morbidity, and mortality in patients with AF. We explored outcomes by DM status and randomized anticoagulant in a large AF trial. Methods: 21,105 patients in ENGAGE AF-TIMI 48 trial were stratified into pre-specified categories: no-DM (n=13481); non-insulin dependent DM (NIDDM, n=6354); and IDDM (n=1270). We compared efficacy, safety, and net outcomes adjusted for baseline differences across the 3 groups. We assessed for effect modification by DM status on the relative efficacy and safety of edoxaban vs warfarin. The primary endpoints were stroke/SEE and ISTH major bleeding. Results: Patients with IDDM were younger (mean age 68.8 vs 69.5 vs 71.3 yrs) and had higher BMIs (32.9 vs 31.0 vs 28.4kg/m2) and CHA2DS2-VASc scores (mean 4.8 vs 4.6 vs 4.2) as compared to those with NIDDM or no-DM (each P<0.001). Patients with IDDM (adj HR 1.46, p=0.004), but not those with NIDDM (adj HR ...
TL;DR: SCD is the most common cause of cardiovascular death in patients with atrial fibrillation and has several distinct predictors, some of which are modifiable, which may be considered in planning research and treatment strategies for patients withAtrial Fibrillation.
TL;DR: Whether the trend of decreasing mortality has continued in the last decade is sought and the relative contributions of changing comorbid status, clinical risk profile at presentation, and acute medical and interventional treatments to changing outcomes in patients with NSTEMI are examined.
Abstract: Cardiovascular disease remains the largest contributor to global mortality, accounting for nearly half of the 36 million annual deaths from noncommunicable diseases, making it a major priority for global health policy initiatives.1,2 In developed countries, mortality due to cardiovascular disease has declined approximately 50% to 80% during the late 20th and early 21st centuries.3 This success story is most certainly multifactorial. The last several decades have witnessed substantial advances in the understanding of the causative factors and pathophysiology underlying vascular disease, allowing for targeted approaches to risk factor reduction for primary prevention (eg, blood pressure and cholesterol control) as well as effective strategies for management of acute events and for secondary prevention of recurrent events. Incremental benefit was seen even during the last decade with the introduction of risk stratification tools to guide decisions regarding early invasive coronary strategies, more potent antiplatelet therapies, and improved drug-eluting stent technologies.4-6 As such, it appears that there has been both a reduction in the incidence of cardiovascular events and a decrease in event-related fatality rates. For example, the WHO MONICA study of predominantly high-income countries reported a 4% annual decline in death rates due to coronary heart disease. Approximately 75% of the decrease was attributed to a reduction in coronary event rates, reflecting risk factor modification, and the remainder was due to a decrease in case-fatality rates related to improvements in acute medical and secondary preventive therapy.7 Randomized trials are the source of robust evidence for the benefit of and interplay between pharmacological treatments and invasive coronary strategies in managing acute coronary syndrome.4,5 After incorporation of these therapies into guidelines, investigators typically use registries to describe adherence to guideline-based treatments and to ascertain whether adherence is associated with changes in outcomes in the community. For example, a study of the Global Registry of Acute Coronary Events (GRACE) registry between 1999 and 2006 found that use of guideline-recommended treatments such as acute pharmacotherapy (eg, β-blockers, statins, and thienopyridines) and percutaneous coronary intervention (PCI) increased significantly among patients with non–ST-elevation myocardial infarction (NSTEMI); taken together, these changes were associated with a 33% riskadjusted decrease in death (from 4.9% to 3.3%) at 6 months.8 Despite several studies evaluating the association between adherence to guideline-based strategies and outcomes, the relative importance of the individual therapies (eg, invasive coronary approach vs pharmacotherapies) and the clinical context of the health care system in which they are applied are less clear. In a related article in JAMA, Hall and colleagues utilized the size and scope of the Myocardial Ischemia National Audit Project (MINAP) database, a national registry of patients with acute coronary syndrome admitted in England and Wales, to investigate the trends in risk profile, treatments, and outcomes among 389 057 patients presenting with NSTEMI between 2003 and 2013.9,10 Specifically, the authors sought to determine whether the trend of decreasing mortality has continued in the last decade and to examine the relative contributions of changing comorbid status, clinical risk profile at presentation, and acute medical and interventional treatments to changing outcomes in patients with NSTEMI. Hall and colleagues describe a 30% relative decrease in unadjusted 6-month all-cause mortality from 10.8% in 2003 to 7.6% in 2013. During this time, there was an increase in the prevalence of many comorbidities, including diabetes, hypertension, emphysema, renal failure, and smoking, but a decline in clinical risk of mortality at the time of acute coronary syndrome presentation as defined by the GRACE risk score (which incorporates age, cardiac arrest, ST-segment deviation, biomarker elevation, blood pressure, heart rate, heart failure, and renal function). Individuals defined as intermediate to high risk (GRACE score ≥88) represented the majority of patients throughout the study period, but with a significant decline in the proportion of patients in this risk group over time (87.2% in 2003-2004 to 82.0% in 2012-2013; P = .01). Adherence to guideline-based therapy was high throughout, with a significant increase in adherence during the 10-year study period. Notably, an invasive coronary strategy, defined as coronary angiography, PCI, or coronary artery bypass graft (CABG) surgery, increased from 42.7% to 78.6% over the course of the study (P < .001). Although the rates of CABG appeared relatively constant at less than 5%, the rates of PCI increased from less than 10% to 33% over time, which consistently represented approximately half of the patients who underwent coronary angiography. Hall and colleagues drew several important conclusions. First, the reduction in mortality persisted after adjustment for (1) the lower clinical risk at presentation as determined by the GRACE risk score; (2) the small but significant improvements in socioeconomic status (as measured by the Index of Multiple Deprivation); and (3) an increasing burden of Related article Opinion