http://www.theheart.org/web_slides/1143997.do A study on Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors (SYNERGY)

1. SYNERGY (Superior Yield of the New
Strategy of Enoxaparin, Revascularization
and Glycoprotein IIb/IIIa Inhibitors)

2. SYNERGY (Superior Yield of the New Strategy of Enoxaparin,
Revascularization and Glycoprotein IIb/IIIa Inhibitors)
K Mahaffey (Duke University, Durham, NC), J Ferguson (Texas Heart Institute, Houston, TX)
American College of Cardiology 2004 Scientific Sessions
• Population and treatment:
10000 high-risk ACS patients (median age of 68)
Randomized to enoxaparin (1mg/kg sc every 12 hours) or UFH (60 U/kg
bolus then 12 U/kg per hr adjusted to an aPTT of 50 to 70 seconds)
• Outcomes:
Primary end point: death/MI at 30 days
Secondary end points: incidence of death or nonfatal MI at 14 days; the
combined incidence of all-cause mortality, nonfatal MI, stroke, or recurrent
ischemia requiring revascularization; and individual components of this
composite at 14 and 30 days after enrollment
Primary safety end point: incidence of major bleeding or stroke
UFH=unfractionated heparin

3. SYNERGY: Results (efficacy)
• Enoxaparin is as effective as UFH in the prevention of the primary end point
Major clinical end points at 30 days
End point Enoxaparin UFH p
(n=4993), % (n=4985), %
Death/MI 14 14.5 NS
Death 3.2 3.1 NS
MI 11.7 12.7 NS
Stroke 1.0 0.9 NS
Hemorrhagic stroke <0.1 <0.1 NS

4. SYNERGY: Results (safety)
• GUSTOa severe bleeding was not significantly different between the two groups
• There was an increase in TIMI major bleeding and in hemoglobin and hematocrit
dropb with enoxaparin
Bleeding outcomes
Bleeding definition Enoxaparin UFH p
(n=4993), % (n=4985), %
GUSTO severe bleeding 2.9 2.4 0.107
Hemoglobin and hematocrit drop/ICH 15.2 12.5 0.001
TIMI major bleeding (all) 9.1 7.6 0.008
TIMI major bleeding (CABG) 6.8 5.9 0.081
TIMI major bleeding (non-CABG) 2.4 1.7 0.025
Transfusions 17.0 16.0 0.155
a. Severe bleeding leading to hemodynamic compromise or intracranial hemorrhage (ICH)
b. Hemoglobin drop more than 5 g/dL or hematocrit drop of 15% or greater

5. SYNERGY: Commentary*
"TIMI major bleeding is not a mickey-mouse end point. I would like to see the data
in detail before deciding whether the bleeding is a serious worry or not. But at the
end of the day, if you have two drugs that give the same benefit but one increases
bleeding, I would think very carefully before using that one."
- Dr Salim Yusuf
"If you look at SYNERGY in isolation, you probably wouldn't use enoxaparin. You
have to look at the totality of the evidence and best way of doing this is without any
crossover."
- Dr Robert Califf (principal investigator)
*All comments from SYNERGY: Enoxaparin as effective as heparin but bleeding may be an issue
(http://www.theheart.org/article/221047.do)

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