Harvard Schering-Plough Workshop

Elliott Antman, M.D.

Cardiovascular Division, Brigham and Women's Hospital;
Professor of Medicine, Harvard Medical School, Boston, MA;
Director, Harvard Postgraduate Education Program in Clinical and Translational Science

Global Trials: Experience in Cardiovascular Medicine 

Abstract

Unfractionated heparin is often used as adjunctive therapy with fibrinolysis in patients with ST-elevation myocardial infarction. We compared a low-molecular-weight heparin, enoxaparin, with unfractionated heparin for this purpose. We randomly assigned 20,506 patients (674 sites, 48 countries) with ST-elevation myocardial infarction who were scheduled to undergo fibrinolysis to receive enoxaparin throughout the index hospitalization or weight-based unfractionated heparin for at least 48 hours. The primary efficacy end point was death or nonfatal recurrent myocardial infarction through 30 days. The primary end point occurred in 12.0 percent of patients in the unfractionated heparin group and 9.9 percent of those in the enoxaparin group (17 percent reduction in relative risk, P<0.001). Major bleeding occurred in 1.4 percent and 2.1 percent, respectively (P<0.001).

Outcomes in patients with ST-elevation myocardial infarction (STEMI) differ between those in clinical trials and those in routine practice, as well as across different regions. We hypothesized that adjustment for baseline risk would minimize such variations. A total of 3726 patients were registered from 109 sites in 25 countries.  Patients in the registry had a higher baseline risk than those in the trial; they had more extensive prior cardiac histories and more comorbidities. Unadjusted in-hospital mortality was higher in the registry (8.3%) than in the trial (6.6%) (hazard ratio, 1.30; P <0.001); however, after adjusting for TIMI Risk Index, mortality was similar (hazard ratio adj, 1.00; P = 0.97). The GNI was not significantly predictive of in-hospital mortality in the multivariable model of the registry.

Biosketch

Dr. Elliott M. Antman is a senior faculty member in the Cardiovascular Division of the Brigham and Women's Hospital in Boston, Massachusetts. Having devoted his career to academic medicine, he is Professor of Medicine at Harvard Medical School. During his tenure at the Brigham and Women’s Hospital,  Dr. Antman has been recognized for his active role and interest in education and training. He is the recipient of many awards from the housestaff, regularly participates in Professor’s Rounds at the Brigham and Women’s Hospital, and has been honored for his contributions by the Harvard Medical School when it awarded him the A. Clifford Barger Excellence in Mentoring Award in 2001. As of 2009 he was named the Director of the Harvard Catalyst Postgraduate Program in Clinical and Translational Science. Dr. Antman is a Senior Investigator in the Thrombolysis in Myocardial Infarction (TIMI) Study Group. He has published on the use of serum cardiac markers for diagnosis and prognosis of patients with unstable angina and acute myocardial infarction, cyclooxygenase and cardiovascular risk, and antithrombotic therapy for acute coronary syndromes. Dr. Antman is a Senior Associate Editor of Circulation. He was selected to be the Series Editor for the AHA Clinical Series, a guideline-based monograph series. Dr. Antman has been an active participant in AHA and ACC activities, locally and nationally. He was the Chairman of the joint ACC/AHA Task Force on Practice Guidelines from January 2003 through December 2005.