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

Welcome Welcome Ask The ExpertsAsk The Experts

March 24-27, 2007March 24-27, 2007

New Orleans, LANew Orleans, LA

Is It Safe To Switch Between Antithrombins?Is It Safe To Switch Between Antithrombins?

C. Michael Gibson, M.S., M.D.C. Michael Gibson, M.S., M.D.C. Michael Gibson, M.S., M.D.C. Michael Gibson, M.S., M.D.

DefinitionsDefinitions

• Switching: A change in antithrombins Switching: A change in antithrombins before randomizationbefore randomization

• Cross-Over: A change in antithrombins Cross-Over: A change in antithrombins after randomizationafter randomization

Gibson CM, Am J Cardiol 2007 in pressGibson CM, Am J Cardiol 2007 in press

No prior

UFH

Enox

Both

Pre-randomization Randomization Crossover

Lesson From SYNERGYLesson From SYNERGY

• Switching: A change in antithrombins Switching: A change in antithrombins before randomization was not before randomization was not associated with excess bleedingassociated with excess bleeding

• Cross-Over: A change in antithrombins Cross-Over: A change in antithrombins after randomization was associated with after randomization was associated with excess bleedingexcess bleeding


Confusion Surrounding “Crossover”Confusion Surrounding “Crossover”

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

Association of Pre-Randomization Anticoagulant Switching with Bleeding in the

Setting of Percutaneous Coronary Intervention: A REPLACE-2 Analysis

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 The goal of this analysis was to evaluate whether a hazard existed evaluate whether a hazard existed when either unfractionated heparin or when either unfractionated heparin or low molecular weight heparin were low molecular weight heparin were administered prior to study medication administered prior to study medication in the REPLACE-2 trial. 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


Pre-Randomization Anticoagulant Switching and Bleeding


• The present study compared bleeding The present study compared bleeding among patients treated with either among patients treated with either preceding anti-thrombin therapy or no preceding anti-thrombin therapy or no preceding anti-thrombin therapy in the preceding anti-thrombin therapy in the prior 48 hours. prior 48 hours.


VariableNaive→BIV*

(n=2,345)

UFH→BIV

(n=287)

LMWH→BIV

(n=258)

Naive→GP IIbIIIa

/UFH(n=2,325)

UFH→GP IIbIIIa/U

FH(n=349)

LMWH→GP IIbIIIa/UFH

(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%

Bleeding and Switching in REPLACE-2Bleeding 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)


• The method of switching or The method of switching or transition involved administration of transition involved administration of bivalirudin > 8 hours after last low bivalirudin > 8 hours after last low molecular weight heparin dose or > 6 molecular weight heparin dose or > 6 hours after unfractionated heparin, hours after unfractionated heparin, unless in the case of unfractionated unless in the case of unfractionated heparin therapy the activated partial heparin therapy the activated partial thromboplastin time was ≤ 50 thromboplastin time was ≤ 50 seconds or the activated clotting seconds or the activated clotting time was ≤ 175 seconds.time was ≤ 175 seconds.




How to SwitchHow to Switch

Switching and 1 Year MortalitySwitching and 1 Year Mortality



• When switching was undertaken in When switching was undertaken in this fashion, preceding therapy with this fashion, preceding therapy with either low molecular weight heparin either low molecular weight heparin or unfractionated heparin was not or unfractionated heparin was not associated with an excess of associated with an excess of bleeding or transfusions compared bleeding or transfusions compared with bivalirudin therapy alone in the with bivalirudin therapy alone in the cardiac catheterization laboratory.cardiac catheterization laboratory.

• This analysis was confined to the This analysis was confined to the phenomenon of pre-randomization phenomenon of pre-randomization “switching” rather than post-“switching” rather than post-randomization “crossover”. randomization “crossover”.




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

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