1. Welcome
Ask The Experts
March 24-27, 2007
New Orleans, LA

2. Is It Safe To Switch Between Antithrombins?
C. Michael Gibson, M.S., M.D.

3. Switching: A change in antithrombins before randomization
Definitions
Switching: A change in antithrombins before randomization
Cross-Over: A change in antithrombins after randomization
Gibson CM, Am J Cardiol 2007 in press

4. Pre-randomization
Randomization
Crossover
No prior
UFH
Enox
Both

5. Lesson From SYNERGY
Switching: A change in antithrombins before randomization was not associated with excess bleeding
Cross-Over: A change in antithrombins after randomization was associated with excess bleeding
Gibson CM, Am J Cardiol 2007 in press

6. Confusion Surrounding “Crossover”
In the analysis of post-randomization “crossover”, it not clear in studies whether bleeding or ischemia caused the patient to “crossover”, or alternatively whether the “crossover” caused the patient to have a bleeding or ischemic event.

7. Association of Pre-Randomization Anticoagulant Switching with Bleeding in the Setting of Percutaneous Coronary Intervention: A REPLACE-2 Analysis
C. Michael Gibson, Yuli Ten, Sabina A. Murphy, Lauren N. Ciaglo, Matthew C. Southard, A. Michael Lincoff, and Ron Waksman
The goal of this analysis was to evaluate whether a hazard existed when either unfractionated heparin or low molecular weight heparin were administered prior to study medication in the REPLACE-2 trial.
Gibson CM, Am J Cardiol 2007 in press

8. Pre-Randomization Anticoagulant Switching and Bleeding
The present study compared bleeding among patients treated with either preceding anti-thrombin therapy or no preceding anti-thrombin therapy in the prior 48 hours.
Gibson CM, Am J Cardiol 2007 in press

9. Bleeding and Switching in REPLACE-2
Variable
Naive→BIV*
(n=2,345)
UFH→
BIV
(n=287)
LMWH→
(n=258)
Naive→
GP IIbIIIa
/UFH
(n=2,325)
GP IIbIIIa/UFH
(n=349)
(n=313)
Protocol Major Bleed
2.3%*
1.7%
2.7%
3.6%
4.9%
5.8%
Protocol Minor Bleed
13.4%*
13.6%
14.0%
25.0%
28.9%
29.1%
Protocol Major/Minor Bleed
15.6%*
15.3%
16.7%
28.6%**
33.8%
34.8%
TIMI Major/Minor Bleed
1.9%*
1.4%
1.9%
3.5%
4.3%
5.4%
≥2 Non-CABG Transfusions
0.8%*
1.1%
1.2%
1.0%**
2.3%
2.9%
* p=NS for all 3-way comparisons vs BIV alone
** p<0.05 for 3-way comparison vs glycoprotein IIbIIIa (GP IIbIIIa), unfractionated heparin (UFH) naïve as well as 2-way comparisons of unfractionated heparin (UFH) naïve vs either preceding unfractionated heparin (UFH) or preceding low molecular weight heparin (LMWH)
Gibson CM, Am J Cardiol 2007 in press

10. Pre-Randomization Anticoagulant Switching and Bleeding
The method of switching or transition involved administration of bivalirudin > 8 hours after last low molecular weight heparin dose or > 6 hours after unfractionated heparin, unless in the case of unfractionated heparin therapy the activated partial thromboplastin time was ≤ 50 seconds or the activated clotting time was ≤ 175 seconds.
Gibson CM, Am J Cardiol 2007 in press

11. How to Switch

12. Switching and 1 Year Mortality

13. Pre-Randomization Anticoagulant Switching and Bleeding
When switching was undertaken in this fashion, preceding therapy with either low molecular weight heparin or unfractionated heparin was not associated with an excess of bleeding or transfusions compared with bivalirudin therapy alone in the cardiac catheterization laboratory.

14. Pre-Randomization Anticoagulant Switching and Bleeding
This analysis was confined to the phenomenon of pre-randomization “switching” rather than post-randomization “crossover”.
Gibson CM, Am J Cardiol 2007 in press

15. Question
&
Answer

16. Thank You!
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