Elliott M. Antman

Bio: Elliott M. Antman is an academic researcher from Brigham and Women's Hospital. The author has contributed to research in topics: Myocardial infarction & TIMI. The author has an hindex of 161, co-authored 716 publications receiving 179462 citations. Previous affiliations of Elliott M. Antman include Duke University & Katholieke Universiteit Leuven.

Efficacy and safety of edoxaban compared with warfarin according to the burden of diseases in patients with atrial fibrillation: insights from the ENGAGE AF-TIMI 48 trial

Abstract: Aims 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 and results In a post hoc analysis of the ENGAGE AF-TIMI 48 trial, we analysed 21 105 patients with AF followed for an average of 2.8 years and randomized to either a higher-dose edoxaban regimen (HDER), a lower-dose edoxaban regimen, or warfarin. We used the updated Charlson Comorbidity Index (CCI) to stratify the patients according to the burden of concomitant disease (CCI = 0, 1, 2, 3, and ≥4). The treatment groups were then compared for safety, efficacy, and net clinical outcomes across CCI categories. There were 32.0%, 7.3%, 42.1%, 12.7%, and 6.0% of patients with CCI scores of 0, 1, 2, 3, and ≥4, respectively. A CCI score ≥4 was associated with significantly higher rates of thromboembolic events, bleeding, and death compared to CCI = 0 (P 0.10 for each). Conclusion Although increasing CCI scores are associated with worse outcomes, the efficacy, safety, and net clinical outcomes of edoxaban vs. warfarin were independent of the degree of comorbidity present.

Glycoprotein IIb/IIIa inhibitors in acute ST segment elevation myocardial infarction.

Abstract: Limitations in the standard treatment of acute myocardial infarction have focused attention on inhibition of platelet activity by its final common pathway of activation, the glycoprotein IIb/IIIa receptor. Animal studies have suggested that a glycoprotein IIb/IIIa inhibitor could accelerate thrombolysis and prevent reocclusion after successful thrombolysis. Studies evaluating the use of a glycoprotein IIb/IIIa inhibitor alone without thrombolysis or percutaneous transluminal coronary revascularization do not suggest that isolated use of glycoprotein IIb/IIIa inhibitors restores TIMI 3 flow in a sufficient proportion of patients. Clinical studies evaluating the combination of thrombolytic therapy and glycoprotein IIb/IIIa inhibitors appear most promising, with evidence of improved angiographic outcomes. Reducing the dose of thrombolytic agents may result in reduction in bleeding risk. Current and future trials will investigate reduced-dose reteplase with abciximab and eptifibatide with reduced-dose alteplase. Available evidence suggests that glycoprotein IIb/IIIa inhibition may facilitate thrombolysis, thus adding a new element to future reperfusion regimens.

Standards for Clinical Research: Keeping Pace With the Technology of the Future.

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 …

Measuring inconsistency in meta-analyses

Abstract: Cochrane Reviews have recently started including the quantity I 2 to help readers assess the consistency of the results of studies in meta-analyses. What does this new quantity mean, and why is assessment of heterogeneity so important to clinical practice? Systematic reviews and meta-analyses can provide convincing and reliable evidence relevant to many aspects of medicine and health care.1 Their value is especially clear when the results of the studies they include show clinically important effects of similar magnitude. However, the conclusions are less clear when the included studies have differing results. In an attempt to establish whether studies are consistent, reports of meta-analyses commonly present a statistical test of heterogeneity. The test seeks to determine whether there are genuine differences underlying the results of the studies (heterogeneity), or whether the variation in findings is compatible with chance alone (homogeneity). However, the test is susceptible to the number of trials included in the meta-analysis. We have developed a new quantity, I 2, which we believe gives a better measure of the consistency between trials in a meta-analysis. Assessment of the consistency of effects across studies is an essential part of meta-analysis. Unless we know how consistent the results of studies are, we cannot determine the generalisability of the findings of the meta-analysis. Indeed, several hierarchical systems for grading evidence state that the results of studies must be consistent or homogeneous to obtain the highest grading.2–4 Tests for heterogeneity are commonly used to decide on methods for combining studies and for concluding consistency or inconsistency of findings.5 6 But what does the test achieve in practice, and how should the resulting P values be interpreted? A test for heterogeneity examines the null hypothesis that all studies are evaluating the same effect. The usual test statistic …

The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration

Abstract: Systematic reviews and meta-analyses are essential to summarize evidence relating to efficacy and safety of health care interventions accurately and reliably. The clarity and transparency of these reports, however, is not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (QUality Of Reporting Of Meta-analysis) Statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realizing these issues, an international group that included experienced authors and methodologists developed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA Statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this Explanation and Elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA Statement, this document, and the associated Web site (http://www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.

Abstract: "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount.

Cochrane Handbook for Systematic Reviews of Interventions

Abstract: The Cochrane Handbook for Systematic Reviews of Interventions is the official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions.