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.

Trials and tribulations of thrombin inhibition.

Abstract: Trials and tribulations of thrombin inhibition Thrombin is a central component in the molecular and cellular response to plaque rupture and therefore pertinent to the entire spectrum of acute coronary syndromes. This serine protease not only promotes the deposition of fibrin strands and further activation of the coagulation cascade, but is also a potent stimulus for platelet activation, induction of adhesion molecules by neutrophils and monocytes, and proliferation of vascular smooth muscle cells. The current regimen of combined antithrombin and antiplatelet therapy with heparin and aspirin, respectively, across the spectrum of acute coronary syndromes is based on the pivotal role played by thrombin as well as activated platelets (to whose activation thrombin also contributes). However, this is not an ideal regimen. Aspirin is a relatively weak antiplatelet agent and the promise of more potent agents is being fulfilled by the platelet glycoprotein Ilbllla receptor inhibitors. Heparin also leaves much to be desired. It is an indirectly acting drug that catalyzes the inactivation of fluid phase thrombin by antithrombin III, but is unable to inhibit clot-bound thrombin, which therefore remains enzymatically active. In addition to this deficiency, heparin has several other theoretical disadvantages including inhibition by platelet factor IV and marked heterogeneity of its pharmaco-kinetic and pharmacodynamic properties. Considerable effort has been expended in identifying a safe and effective antithrombin that can inhibit both fluid phase and clot-bound thrombin. The medicinal leech, hirudo medicinalis, is the source of hirudin, a 65 amino acid compound that binds directly in a 1:1 fashion via its carboxy terminus to the substrate recognition site of thrombin and via its amino terminus to the catalytic centre of thrombin. Nonsulfated forms of hirudin have been produced by recombinant technology by Ciba-Geigy (CGP 39393 also referred to as REVASC® or desi-rudin) and Hocchst Behringwerke (HBW 023) that are nearly identical in structure and activity to the naturally occurring compound 1 ' 1. In experimental studies of coronary thrombosis, hirudin was superior to heparin in facilitating thrombolysis with both tPA and streptokinase' 2 ' 31. Additionally, hirudin was more effective than heparin in preventing thrombus deposition in animal models of deep arterial injury 141. Pilot studies of patients with stable angina, unstable angina, and acute MI consistently observed that hirudin was more likely than heparin to maintain a stable aPTT in the target range, thus potentially avoiding the periods of inadequate and excessive anticoagulation frequently seen with heparin. Angio-graphic …

Beneficial effects of intravenous glyceryl trinitrate in a case of Prinzmetal angina.

Abstract: A case is described of the successful use of intravenous glyceryl trinitrate in controlling ischaemia-induced high-grade ventricular ectopic activity occurring in a patient during a Prinzmetal angina attack. The intravenous form of glyceryl trinitrate is probably more effective than the sublingual form in controlling arrhythmias arising during acute ischaemic episodes because of prompt delivery of the drug to the coronary circulation where vasodilation occurs. In addition,the ability to control the quantity and rate of drug delivery with an intravenous infusion offers distinct advantages in cases of coronary spasm occurring during situations such as coronary arteriography where it can be administered with careful electrocardiographic and haemodynamic monitoring.

Individual Patient-Level Data Sharing for Continuous Learning: A Strategy for Trial Data Sharing.

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

Documented symptomatic bradycardia and symptom relief in patients receiving permanent pacemakers: an evaluation of the joint ACC/AHA pacing guidelines.

Abstract: Recently, emphasis has been placed on documenting symptomatic bradycardia (DSB) before pacemaker placement can be justified in some patients. This study was designed to judge whether DSB improved the likelihood of symptom relief after pacing in 93 patients who had symptoms prior to pacing. Patients with complete heart block (Group A) had excellent symptomatic relief with or without pre-pacemaker DSB (100% vs 94%, P = NS). Patients with other diagnoses (Group B) also had a high incidence of symptomatic relief after pacing, regardless of whether or not DSB was present pre-implant (28/30 (93%) vs 23/28 (82%) P = NS). When evaluated as a test to predict the response to pacing for Group B patients, spontaneously occurring symptomatic bradycardia was neither highly sensitive (55%) nor highly specific (71%). Moreover, while the ability of a positive test to predict resolution of symptoms after pacing was high (93%), the ability of a negative test to predict a poor outcome after pacing was low (18%). The absence of DSB should not rule out permanent pacing for symptomatic patients in any diagnostic group. Future pacing guidelines should be revised to offer additional detail regarding the influence of symptoms, extent of asymptomatic bradycardia, and results of provocative tests in determining which implants should be classified as definitely indicated.

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.