P rof . dr sc. Mirza Dili ć, FESC, FACC Klinički Centar Sarajevo šef Centra

1. Nova antitrombotska terapija Prof. dr sc. MirzaDilić, FESC, FACC Klinički Centar Sarajevo šef Centra za srce direktor Internih Klinika i Odjeljenja

6. Dva tipa tromboze • Venski tromboembolizam • (dominantno preko trombina) • Aterotromboza • (dominantno preko trombocita)

7. VTE - venski tromboembolizam • DVT (duboka venska tromboza) • PE (plućna embolija) • Profilaksa • Tretman

8. VTE - venski tromboembolizam • DVT (duboka venska tromboza) • PE (plućni tromboembolizam) • AT (atrijalni trombi)

13. Centralno mjesto trombina i trombocita

14. Thrombin ~ antitrombin III Antitrombin III

15. Antiagregantni faktor Antiagregantni faktor

16. Standardna terapija • Warfarin, acenokumarol....... • Heparin • LMW Heparin • Aspirin • Dipiridamol • Tiklopidin • Klopidogrel

17. Anti vitamin K - AVK per oralni antikoagulansi • PO • Inhibira protrombinski kompleks • Warfarin, marivarin, acenokumarol • Potreban monitoring PT i INR • INR izmedju 2,0 i 3,0 • Komplikacija krvarenje • Antidot

18. Propisivanje VKA u AF No anticoagulation VKAs 64% 67% 55% N=11,409 ATRIA cohort3(managed care system,California, USA) N=23,657 Medicare cohort, USA1 N=5,333 EuroHeart survey2

19. Novel antithrombotics

20. FDA approval EMA approval Appropriate balansing between clinical benefit and risk of bleeding.

21. Safety Similarrates of bleeding and adverse events Less CVI and fatal GI bleeding FDA approval

23. Direct inhibitor Xa - Rivaroxaban • Rivaroxaban vs. warfarin • VTE, AF, ACS • Ortopedska hirurgija • Redukcija trombotskih komplikacija • Kontrolisano krvarenje

24. Direct inhibitor Xa - Rivaroxaban • Rivaroxaban vs. warfarin • VTE, AF, ACS • Ortopedska hirurgija • Redukcija trombotskih komplikacija • Kontrolisano krvarenje RECORD Trial (VTE – HR, KR) 1x10 MAGELLAN Trial (VT) 1x10 ROCKET Trial (AF)1x15, 1x20 EINSTEIN Trial (VTE) 2x15 ATLAS ACS TIMI 2 (ACS) 2 x 2,5, 2 x 5

25. Direct inhibitor Xa - Apixaban • Apixaban vs warfarin • ACS, VTE, AF, • Ortopedska hirurgija • Redukcija VTE komplikacija • Kontrolisano krvarenje ADVANCE Trial (HR) 2x2,5 AVVEROES (AF) 2x5 ARISTOTLE (AF) 2x5 APPRAISE 2 (ACS) 2x5

26. Apixaban European Medicines Agency advisory committee has "recommended approval" of anti-clotting drug apixaban for use in patients with "atrial fibrillation if it's not caused by a heart valve problem." If the EMA take the panel's advice and apixaban is approved, it would be eligible for "sales in all 27 European Union member states, as well as Iceland and Norway."

28. Direct thrombin inhibitorDabigatran • Dabigatran • VTE, AF, ACS • Ortopedska hirurgija • Redukcija trombotskih komplikacija • Kontrolisano krvarenje RE-LY Trial RE-COVER Trial

29. Dabigatran 150 mg. twice daily Dabigatran 75 mg. daily FDA approval

30. Prasugrel Ticagrelor Cangrelor (I.V) Novel antiplatelets

31. ADP inhibitor • 5-9 x jači effect od clopidogrela • 60 mg. loading dose + 10 mg dn. • Efficacy – bleeding risk Prasugrel

32. ADP direktni inhibitor - subtip P2Y12 • Reverzibilan inhibitor • Ne aktivira se preko jetre • 180 mg loading dose + 2 x 90 mg doza maintance • Efficacy – bleeding risk Ticagrelor

33. ACCPGuidelines 2012

34. CHEST 2012 9 ed.Executive Summary Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines Guyatt GH, MD, FCCP,  Aki EA, MD, PhD, MPH, Crowther M, MD, Gutterman DD, MD, FCCP, Schuemann HJ, MD, PhD, FCCP, and for theAmerican College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel*

35. For patients with AF, including those with paroxysmal AF, who are at low risk of stroke (eg, CHADS2 [congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score = 0), we suggest no therapy rather than antithrombotic therapy (Grade 2B). For patients who do choose antithrombotic therapy, we suggest aspirin (75 mg to 325 mg once daily) rather than oral anticoagulation (Grade 2B) or combination therapy with aspirin and clopidogrel (Grade 2B). Antithrombotic Therapy for Atrial Fibrillation Nonrheumatic Atrial Fibrillation (AF)

36. For patients with AF, including those with paroxysmal AF, who are at intermediate risk of stroke(eg, CHADS2 score = 1), we recommend oral anticoagulationrather than no therapy (Grade 1B). We suggest oral anticoagulation rather than aspirin (75 mg to 325 mg once daily) (Grade 2B) or combination therapy with aspirin and clopidogrel (Grade 2B). For patients who are unsuitable for or choose not to take an oral anticoagulant (for reasons other than concerns about major bleeding), we suggest combination therapy with aspirin and clopidogrel rather than aspirin (75 mg to 325 mg once daily) (Grade 2B). . AF and intermediate risk of stroke

37. For patients with AF, including those with paroxysmal AF, who are at high risk of stroke (eg, CHADS2 score = 2), we recommend oral anticoagulation rather than no therapy (Grade 1A), aspirin (75 mg to 325 mg once daily) (Grade 1B), or combination therapy with aspirin and clopidogrel (Grade 1B). For patients with AF, including those with paroxysmal AF, for recommendations in favor of oral anticoagulation we suggest dabigatran 150 mg twice daily rather than adjusted-dose VKA therapy (target INR range, 2.0-3.0) (Grade 2B). AF and high risk of stroke

38. Strictly fixed ? • Non-Responder? • Hyper-Responder ? Dosage ???

40. ACC / AHA / ESC Guidelines Update 2012 2012