A subgroup analysis of the impact of prerandomization antithrombin therapy on outcomes in the SYNERGY trial: enoxaparin versus unfractionated heparin in non-ST-segment elevation acute coronary syndromes.
OBJECTIVE
The purpose of this study was to compare the effect of receiving pretreatment with antithrombin before randomization as well as overall efficacy and safety of enoxaparin versus unfractionated heparin (UFH) in the SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors) trial.


BACKGROUND
The SYNERGY trial results demonstrated noninferiority in outcomes with enoxaparin compared with UFH. Randomized treatment was independent of prerandomization treatment.


METHODS
Analyses were first performed on the 4 prerandomization subgroups: patients who received no antithrombin therapy and those who were treated with enoxaparin or UFH or both. Then, we focused on the subgroup of patients who received no pretreatment or were pretreated with and randomized to the same drug. Of the 9,978 patients, 2,440 did not receive prerandomization therapy and 6,138 received consistent therapy through randomization. The primary end point was the composite of death and nonfatal myocardial infarction (MI) at 30 days.


RESULTS
After adjustment for differences among the subgroups, no significant difference in the association between the 4 pretreatment groups and death or MI remained (p = 0.171). The randomized treatment effect on 30-day death or MI tended to vary with pretreatment (p = 0.055 for interaction test after adjustment). Patients who received consistent therapy with enoxaparin had significantly less death or MI than patients randomized to UFH (adjusted p = 0.041) with a trend toward increased bleeding.


CONCLUSIONS
Treatment with antithrombin therapy before randomization had potential impact on comparison of study drug effects. After adjustment for differences in baseline characteristics between subgroups, consistent therapy with enoxaparin might be superior to UFH in reducing death or nonfatal MI, with a modest excess in bleeding.
Cohen
Marc
M
HEART Hospital of New Jersey, Newark Beth Israel Medical Center, Newark, New Jersey 07112, USA. marcohen@SBHCS.com
Mahaffey
Kenneth W
KW
Pieper
Karen
K
Pollack
Charles V
CV
Antman
Elliott M
EM
Hoekstra
James
J
Goodman
Shaun G
SG
Langer
Anatoly
A
Col
Jacques J
JJ
White
Harvey D
HD
Califf
Robert M
RM
Ferguson
James J
JJ
D000368:Aged; D003324:Coronary Artery Disease / Q000150:complications* / Q000601:surgery; D017984:Enoxaparin / Q000627:therapeutic use*; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality / Q000517:prevention & control*; D009204:Myocardial Revascularization; D016896:Treatment Outcome
D017984:Enoxaparin; D005343:Fibrinolytic Agents; D006493:Heparin