Author Affiliations: Duke Clinical Research Institute, Durham, NC (Drs Petersen, Mahaffey, Hasselblad, Blazing, Harrington, and Califf); Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, Mass (Drs Antman and Braunwald); Division of Cardiology, Newark Beth Israel Medical Center, Newark, NJ (Dr Cohen); Canadian Heart Research Centre and Terrence Donnelly Heart Centre, Division of Cardiology, St Michael's Hospital, University of Toronto, Toronto, Ontario (Drs Goodman and Langer); Division of Cardiology, University of Texas, Southwestern, Dallas (Dr de Lemos); Aventis Inc, Bridgewater, NJ (Dr Nessel, Ms Le-Moigne-Amrani); and St Luke's-Episcopal Hospital, Texas Heart Institute, Houston (Dr Ferguson).
Context Antithrombin therapy has become a guidelines-recommended standard of
care in the treatment of acute coronary syndromes (ACS), but recent trials
comparing use of enoxaparin and unfractionated heparin in ACS have yielded
less robust efficacy and safety results than have earlier trials of these
Objective To systematically evaluate the end points of all-cause death and nonfatal
myocardial infarction (MI), transfusion, and major bleeding observed in the
6 randomized controlled trials comparing enoxaparin and unfractionated heparin
in treatment of ACS.
Data Sources The primary data sets for ESSENCE, A to Z, and SYNERGY were available
at the Duke Clinical Research Institute. Baseline characteristics and event
frequencies for TIMI 11B, ACUTE II, and INTERACT were provided by the principal
investigator of each study.
Study Selection All 6 randomized controlled trials comparing enoxaparin and unfractionated
heparin in non–ST-segment elevation ACS were selected for analysis.
Data Extraction Efficacy and safety end points were extracted from the overall trial
populations and the subpopulation receiving no antithrombin therapy prior
Data Synthesis Systematic evaluation of the outcomes for 21 946 patients was performed
using a random-effects empirical Bayes model. No significant difference was
found in death at 30 days for enoxaparin vs unfractionated heparin (3.0% vs
3.0%; odds ratio [OR], 1.00; 95% confidence interval [CI], 0.85-1.17). A statistically
significant reduction in the combined end point of death or nonfatal MI at
30 days was observed for enoxaparin vs unfractionated heparin in the overall
trial populations (10.1% vs 11.0%; OR, 0.91; 95% CI, 0.83-0.99; number needed
to treat, 107). A statistically significant reduction in the combined end
point of death or MI at 30 days was also observed for enoxaparin in the populations
receiving no prerandomization antithrombin therapy (8.0% vs 9.4%; OR, 0.81;
95% CI, 0.70-0.94; number needed to treat, 72). No significant difference
was found in blood transfusion (OR, 1.01; 95% CI, 0.89-1.14) or major bleeding
(OR, 1.04; 95% CI, 0.83-1.30) at 7 days after randomization in the overall
safety population or in the population of patients receiving no prerandomization
Conclusion In a systematic overview of approximately 22 000 patients across
the spectrum of ACS, enoxaparin is more effective than unfractionated heparin
in preventing the combined end point of death or MI.
Petersen JL, Mahaffey KW, Hasselblad V, Antman EM, Cohen M, Goodman SG, Langer A, Blazing MA, Le-Moigne-Amrani A, de Lemos JA, Nessel CC, Harrington RA, Ferguson JJ, Braunwald E, Califf RM. Efficacy and Bleeding Complications Among Patients Randomized to Enoxaparin
or Unfractionated Heparin for Antithrombin Therapy in Non–ST-Segment
Elevation Acute Coronary SyndromesA Systematic Overview. JAMA. 2004;292(1):89-96. doi:10.1001/jama.292.1.89