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(Circulation. 1999;100:1602-1608.)
© 1999 American Heart Association, Inc.


Clinical Investigation and Reports

Assessment of the Treatment Effect of Enoxaparin for Unstable Angina/Non–Q-Wave Myocardial Infarction

TIMI 11B–ESSENCE Meta-Analysis

Elliott M. Antman, MD; Marc Cohen, MD; David Radley, MS; Carolyn McCabe, BS; Janet Rush, MD; Jerome Premmereur, MD; Eugene Braunwald, MD; for the TIMI 11B (Thrombolysis In Myocardial Infarction) and ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q-wave Coronary Events) Investigators

From the Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital (E.M.A., C.H.M., E.B.), Boston, Mass; Hahnemann University Hospital (M.C.), Philadelphia, Pa; and Rhône-Poulenc Rorer (D.R., J.R., J.P.), Collegeville, Pa. Rhône-Poulenc Rorer manufactures Lovenox (enoxaparin).

Correspondence to Elliott M. Antman, MD, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115. E-mail eantman{at}rics.bwh.harvard.edu

Background—Two phase III trials of enoxaparin for unstable angina/non–Q-wave myocardial infarction have shown it to be superior to unfractionated heparin for preventing a composite of death and cardiac ischemic events. A prospectively planned meta-analysis was performed to provide a more precise estimate of the effects of enoxaparin on multiple end points.

Methods and Results—Event rates for death, the composite end points of death/nonfatal myocardial infarction and death/nonfatal myocardial infarction/urgent revascularization, and major hemorrhage were extracted from the TIMI 11B and ESSENCE databases. Treatment effects at days 2, 8, 14, and 43 were expressed as the OR (and 95% CI) for enoxaparin versus unfractionated heparin. All heterogeneity tests for efficacy end points were negative, which suggests comparability of the findings in TIMI 11B and ESSENCE. Enoxaparin was associated with a 20% reduction in death and serious cardiac ischemic events that appeared within the first few days of treatment, and this benefit was sustained through 43 days. Enoxaparin's treatment benefit was not associated with an increase in major hemorrhage during the acute phase of therapy, but there was an increase in the rate of minor hemorrhage.

Conclusions—The accumulated evidence, coupled with the simplicity of subcutaneous administration and elimination of the need for anticoagulation monitoring, indicates that enoxaparin should be considered as a replacement for unfractionated heparin as the antithrombin for the acute phase of management of patients with high-risk unstable angina/non–Q-wave myocardial infarction.


Key Words: enoxaparin • heparin • meta-analysis • anticoagulants




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Current Role of Platelet Glycoprotein IIb/IIIa Inhibitors in Acute Coronary Syndromes
JAMA, September 27, 2000; 284(12): 1549 - 1558.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
S. G. Goodman, M. Cohen, F. Bigonzi, E. P. Gurfinkel, D. R. Radley, V. Le Iouer, G. J. Fromell, C. Demers, A. G. G. Turpie, R. M. Califf, et al.
Randomized trial of low molecular weight heparin (enoxaparin) versus unfractionated heparin for unstable coronary artery disease: One-year results of the essence study
J. Am. Coll. Cardiol., September 1, 2000; 36(3): 693 - 698.
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J Am Coll CardiolHome page
E. Braunwald, E. M. Antman, J. W. Beasley, R. M. Califf, M. D. Cheitlin, J. S. Hochman, R. H. Jones, D. Kereiakes, J. Kupersmith, T. N. Levin, et al.
ACC/AHA guidelines for the management of patients with unstable angina and non-st-segment elevation myocardial infarction: A report of the american college of cardiology/ american heart association task force on practice guidelines (committee on the management of patients with unstable angina)
J. Am. Coll. Cardiol., September 1, 2000; 36(3): 970 - 1062.
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Eur Heart JHome page
M.E Bertrand, M.L Simoons, K.A.A Fox, L.C Wallentin, C.W Hamm, E McFadden, P.J de Feyter, G Specchia, and W Ruzyllo
Management of acute coronary syndromes: acute coronary syndromes without persistent ST segment elevation. Recommendations of the Task Force of the European Society of Cardiology: Recommendations of the Task Force of the European Society of Cardiology
Eur. Heart J., September 1, 2000; 21(17): 1406 - 1432.
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E. M. Antman, M. Cohen, P. J. L. M. Bernink, C. H. McCabe, T. Horacek, G. Papuchis, B. Mautner, R. Corbalan, D. Radley, and E. Braunwald
The TIMI Risk Score for Unstable Angina/Non-ST Elevation MI: A Method for Prognostication and Therapeutic Decision Making
JAMA, August 16, 2000; 284(7): 835 - 842.
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E. M. Ohman, C. B. Granger, R. A. Harrington, and K. L. Lee
Risk Stratification and Therapeutic Decision Making in Acute Coronary Syndromes
JAMA, August 16, 2000; 284(7): 876 - 878.
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J Am Coll CardiolHome page
S. Kaul and P. K. Shah
Low molecular weight heparin in acute coronary syndrome: evidence for superior or equivalent efficacy compared with unfractionated heparin?
J. Am. Coll. Cardiol., June 1, 2000; 35(7): 1699 - 1712.
[Abstract] [Full Text] [PDF]


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JWatch Emergency Med.Home page
Meta-Analysis Confirms Benefit of Enoxaparin in Unstable Angina
Journal Watch Emergency Medicine, December 1, 1999; 1999(1201): 4 - 4.
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JWatch GeneralHome page
Low-Molecular-Weight Heparin Improves Outcomes in Unstable Coronary Syndromes
Journal Watch (General), October 22, 1999; 1999(1022): 4 - 4.
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CirculationHome page
E. M. Antman, C. H. McCabe, E. P. Gurfinkel, A. G. G. Turpie, P. J. L. M. Bernink, D. Salein, A. Bayes de Luna, K. Fox, J.-M. Lablanche, D. Radley, et al.
Enoxaparin Prevents Death and Cardiac Ischemic Events in Unstable Angina/Non-Q-Wave Myocardial Infarction : Results of the Thrombolysis In Myocardial Infarction (TIMI) 11B Trial
Circulation, October 12, 1999; 100(15): 1593 - 1601.
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