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

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. 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 • 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. C. Michael Gibson, Yuli Ten, Sabina A. Murphy, Lauren N. Ciaglo, Matthew C. Southard, A. Michael Lincoff, and Ron Waksman 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 * 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! Please make sure to hand in your evaluation and pick up a ClinicalTrialResults.org flash drive