1. 1 Update on antiplatelet and anticoagulant drugs: sticky stuff KFJ Ng May 2011

2. 2 Direct thrombin inhibition

3. 3 Indirect thrombin inhibition Heparin/antithrombin/thrombin complex Heparin Antithrombin Thrombin

4. 4 Direct thrombin inhibition Direct thrombin inhibitor Thrombin

5. 5 Direct thrombin inhibitors hirudin, bivalirudin argatroban dabigatran

6. 6 Dabigatran (Pradaxa) Annu Rev Med 2011;62:41

7. 7 fXa inhibition (anti-Xa)

8. 8 Anti-Xa and thrombus formation?

9. 9 Factor Xa inhibitors Indirect –Fondaparinux (Arixtra) Direct –Rivaroxaban (Xarelto)

10. 10 Fondaparinux (N=1098)LMWH (N=1107) Matisse DVT Fatal PE 5 (0.5 %) 5 (0.5 %) Non-fatal PE or DVT 38 (3.5 %) 40 (3.6 %) Total symptomatic recurrent VTE 43 (3.9 %) 45 (4.1 %) -0.15 %  = 3.5% 0 1.5%-1.8% Fondaparinux - LMWH (95 % CI ) Primary Efficacy Outcome (non-fatal or fatal recurrent VTE to 3 months) Fondaparinux (N=1103)UFH (N=1110) Fondaparinux - UFH (95 % CI ) Matisse PE -1.2%  = 3.5% 0 0.5%-3.0% Fatal PE 16 (1.5 %) 15 (1.4 %) Non-fatal PE or DVT 26 (2.4 %) 41 (3.6 %) Total symptomatic recurrent VTE 42 (3.8 %) 56 (5.0 %) A T I S S E M....... NEJM 2003;349:1695 Ann Intern Med 2004;140:867

11. 11 Matisse DVT Fondaparinux sc LMWH 1.2% 1.1% 3.0% 2.6% 0%2%4%6%8% Major bleedClinically relevant non-major bleed 1.1% 1.3% 5.2% 3.2% 0%2%4%6%8% 3.7 % 4.2 % Principal Safety Outcome Major bleeding during initial treatment Fondaparinux iv UFH Matisse PE A T I S S E M....... 4.5 % 6.3 % NEJM 2003;349:1695 Ann Intern Med 2004;140:867

12. 12 Rivaroxaban (Xarelto) J Clin Pharm Ther 2011;36:111

13. 13 Rivaroxaban (Xarelto) J Clin Pharm Ther 2011;36:111

14. 14 Copyright ©2010 American Heart Association Mackman, N. et al. Arterioscler Thromb Vasc Biol 2010;30:369-371 Targets of new anticoagulant drugs

15. 15 Discontinuation

16. 16 Anti-platelet agents

17. 17 Gp IIb/IIIa (integrin αIIbβ3) antagonists Abciximab (Reopro) Eptifibatide (Integrilin) Tirofiban (Aggrastat)

18. 18 Gp IIb/IIIa antagonists FDA approval PCI –Abciximab –Eptifibatide ACS –Eptifibatide –Tirofiban

19. 19 Circulation 2010;121:171. JCI 2004;113:340. P2Y 12

20. 20 P2Y 12 inhibitors Irreversible –Clopidogrel (Plavix) –Prasugrel (Effient) Reversible –Ticagrelor (Brilinta) –Cangrelor

21. 21 Prasugrel vs Clopidogrel NEJM 2007;357:2001 (TRITON-TIMI 38)

22. 22 Ticagrelor vs Clopidogrel NEJM 2009;361:1045 (PLATO)

23. 23 Cangrelor NEJM 2009;361:2330 (CHAMPION-PLATFORM)

24. 24 Figure 1 The CHAMPION trials reaffirm that pretreatment with a P2Y 12 antagonist is superior to delaying treatment until after the PCI procedure David P. Faxon (2010) Cangrelor for ACS—lessons from the CHAMPION trials Nat. Rev. Cardiol. doi:10.1038/nrcardio.2009.247

25. 25 BRIDGE trial http://www.clinicaltrials.gov/ct2/show/NCT 00767507

26. 26 Nat Rev Drug Discovery 2010;9:154

27. 27 Discontinuation (Gp IIbIIIa)

28. 28 Discontinuation (P2Y 12 )

29. 29 A&A 2011;112:292

30. 30 Monitoring Coagulation –TEG –PT/aPTT Platelet –PFA-100 –Thrombelastography (TEG) Platelet Mapping –VerifyNow

31. 31 EPICT = 188 sec Sensitivity = 88% Specificity = 52%

32. 32 http://www.asra.com/publications- anticoagulation-3rd-edition- 2010.php

33. 33 Thank You