Anti-Thrombotic Review Mid-Year Sales Meeting Bloomington, IN July 13th – 17th

Objectives Review of Hexabrix Anti-thrombotic & Anti-platelet Properties Overview of Other Anti-Thrombotic Therapies used in the Cath Lab Why is this important??

Anti-Thrombotic Review So what happens?

Anti-Thrombotic Review Blood Vessel Endothelium Subendothelium INJURY Collagen VWF Tissue Factor Vaso- constriction Platelet Adhesion & Secretion Coagulation Cascade Thrombin Platelet aggregation Fibrin Haemostatic plug Dr Isobel Ford

Anti-Thrombotic Review So what role does Hexabrix play? 2 3 1 4

Anti-Thrombotic Review So what role does Hexabrix play? 1 Hexabrix, does not activate resting platelets, unlike nonionic monomers. Doesn’t direct platelets to change shape, release pro-coagulant mediators or to adhere to anything. This prevents/delays formation of the platelet clot. 2 Hexabrix binds w/ Thrombin, preventing it from activating platelets; therefore preventing/delaying the formation of the platelet plug. 3 Hexabrix inhibits the generation of thrombin, reducing the amount of thrombin in the system; therefore Hexabrix inhibits the formation of fibrin. 4 These two together prevents/delays the formation of the fibrin mesh.

Anti-Thrombotic Review So, which studies support these properties? (in vitro & animal) 1 Resting Platelet Activation S Heptinstall et al. British Journal of Heamtology. 1998 N Chronos et al. Circulation. 1993 L Melton et al. Acad Rad.1995 JM Idee & C Corot. Fundam Clin Pharmacol. 1999 2 Inhibition of Thrombin and Fibrin Li and Gabriel. Acad Rad. 1997 JJ Ing et al. Radiology. 1989. PM Kopko et al. Radiology. 1990 J Fareed et al. Radiology. 1990 C Corot et al. Blood Coag and Fibrinolysis. 1996 R Al Dieri et al. Journal of Thrombosis and Hemostasis. 2003 CP Markou et al. Thrombo and Heamost. 2001. 3 4

Anti-Thrombotic Review So, the anti-platelet properties support the better clinical profile of Hx. (Clinical) Le Feuvre et al. Cathet Cardiovasc Interv. 2006 CL Grines et al. JACC. 1996.

Anti-Thrombotic Review What about all of the other therapies used in the Cath Lab?

Anti-Thrombotic Review Four types of Anti-Thrombotics Anti-Platelet Anti-coagulant Thrombolytic Non-Medicinal

Anti-Thrombotic Review Anti-Thrombotics Anti-Platelet Decrease Platelet Aggregation & Inhibit Thrombus Formation Effective in arterial circulation Gp IIb/IIIa Inhibitors Abciximab (ReoPro), Eptifibatide (Integrilin) ADP Receptor Inhibitors Clopidigrel (Plavix), Prasugrel (Effient) Prostglandin Receptor Inhibitors Prostacyclin, Treprostinil (Remodulin) COX Inhibitors Acetylsalicyclic Acid/Aspirin No Platelet Activation Ioxaglate (Hexabrix)

Anti-Thrombotic Review Anti-Thrombotics Anti-Coagulant Prevent the growth of a clot 42-78 hours for the effect to fully develop (Heaprin immediate) Vitamin K Antagonists (factor II, VII, IX, X) Warfarin (Coumadin), Acenocoumarol (Sintrom) Direct Thrombin Inhibitors Bivalarudin (Angiomax), Ioxaglate (Hexabrix) Factor Xa Inhibitors Direct Fondaparinox (Arixtra) Heparin LMWH, Enoxaparin (Lovenox)

Anti-Thrombotic Review Anti-Thrombotics Thrombolytics Reduce the size of the clot (dissolve) Administered together with Heparin for 24-48 hours Activates the enzyme plasminogen, clearing the fibrin mesh, making the clot soluble and subject to further degradation Streptokinase, Reteplase (Retavase)

Anti-Thrombotic Review Anti-Thrombotics Anti-Platelet Anti-coagulant Thrombolytic Gp IIb/IIIa Inhibitors Vitamin K Antagonists (factor II, VII, IX, X) Activates the enzyme plasminogen, clearing the fibrin mesh, making the clot soluble and subject to further degradation ADP Receptor Inhibitors Direct Thrombin Inhibitors Direct Thrombin Inhibitors Prostglandin Receptor Inhibitors Factor Xa Inhibitors Factor Xa Inhibitors COX Inhibitors No Platelet Activation No Platelet Activation Heparin Direct

Anti-Thrombotic & Anti-Coagulant Properties If Hexabrix provides the same benefit as these other therapies…. What is the benefit of using Hexabrix too??

Anti-Thrombotic Review Situations where these therapies don’t have time to take effect (ACS Patients) Additive, synergistic effects with Reopro & Plavix If you are already doing everything you can to prevent thrombotic complications, why not use a CM that provides & enhances protection? Simple Choice Significant Clinical Impact

Anti-Thrombotic Review Can you go too far & increase bleeding risk? Localized effect, not systemic No lingering coagulation interference once CM clears the system Marginal impact on activated clotting time