1. www. Clinical trial results.org Heparin Increases Platelet Activation Heparin (yellow strands) makes platelets more reactive to activation by other agonists such as adenosine diphosphate (ADP). Heparin binds to the platelet GP IIb/IIIa receptor. Given the various ways heparin increases platelet activation, its use may actually increase the need for antiplatelet agents. Becker R et al. J Invasive Cardiol. 2003;(suppl):1-15. Sobel M et al. J Vasc Surg. 2001;33:587-594. Xiao Z et al. Circulation. 1998;97:251-256. CM Gibson 2006

2. www. Clinical trial results.org SEM=scanning electron micrograph. *All SEMs were acquired at a magnification of 4000X with the investigator blinded to treatment. Control platelets Platelets treated with Angiomax Platelets treated with UFH Heparin Activates Platelets But Angiomax ® (bivalirudin) Does Not Direct platelet activation by UFH but not by Angiomax* Direct platelet activation by UFH but not by Angiomax* Data on file, The Medicines Company. CM Gibson 2006

3. www. Clinical trial results.org Heparin Increases Platelet Activation in Unstable Angina Patients Reproduced with permission of Xiao Z et al. Circulation. 1998;97:253. P<0.001 Maximum aggregation (%) ADP (0.3125 µM) TRAP (0.625 µM) 0 0 5 5 10 15 20 Pre-heparin Heparin

4. www. Clinical trial results.org34% 38% 34% 42% 25 30 35 40 45 UFHAngiomax Percentage Angiomax ® (bivalirudin) Significantly Decreases Platelet Reactivity Platelet reactivity in response to 1 μM ADP Fibrin binding P-selectin expression P<0.0001 P=0.01 Aggarwal A et al. J Thromb Thrombolysis. 2002;13:161-165.