Σεμινάπιο Ομάδων Δπγαζίαρ ΟΜΑΓΑ ΔΡΓΑΣΙΑΣ ΗΛΔΚΤΡΟΦΥΣΙΟΛΟΓΙΑΣ ΚΑΙ ΒΗΜΑΤΟΓΟΤΗΣΗΣ Κολπική μαπμαπςγή

Transcription

1 Σεμινάπιο Ομάδων Δπγαζίαρ ΟΜΑΓΑ ΔΡΓΑΣΙΑΣ ΗΛΔΚΤΡΟΦΥΣΙΟΛΟΓΙΑΣ ΚΑΙ ΒΗΜΑΤΟΓΟΤΗΣΗΣ Κολπική μαπμαπςγή Δξελίξειρ ζηην ανηιπηκηική αγωγή ζε αζθενείρ με κολπική μαπμαπςγή Ξςδώναρ Σωηήπιορ Μονάδα Δμθπαγμάηων και Καπδιακήρ Ανεπάπκειαρ Β Καπδιολογικό Τμήμα, Γ.Ν.Α. «Ο Δςαγγελιζμόρ»

2 Atrial Fibrillation Projected burden of diagnosed AF in individuals 20 to 99 years of age in Iceland Page 2 Stefansdottir H., et al. Europace. 2011;13:

3 Lifetime risk for development of AF 1 in 4 men and women 40years of age and older Page 3

4 GRACE ACS: Baseline Characteristics Page 4 Fox KAA, et al. JAMA. 2007;

5 AF increases Cardiovascular Risk Page 5 Circulation. 1998;98: Am J Med 2002;113: Heart Rhythm 2004;1: Stroke 1991;22: Neuroepidimiology 2003;22: Circulation 2003;107:

6 Stroke Risk Stratification of AF pts Page 6 Gage BF, et al. JAMA 2001;285:

7 Bleeding and Stroke Risk Shared risk factors Page 7 Pisters R, et al. Chest 2010:138;

8 Page 8 Vitamin K Antagonist Therapy

9 Narrow therapeutic window of Warfarin Page 9 Hylek EM, et al. Ann Intern Med 1994;120: Hylek EM, et al. N Engl J Med 1996;335:

10 Targets of Anticoagulation Page 10 J Thromb Haemost 2005;3:

11 Page 11 Novel Oral Agents

12 RE-LY: a non-inferiority trial PROBE design, prospective, randomized, open, blinded-endpoint evaluation Page 13 Connolly SJ, et al. N Engl J Med 2009;361:

13 RE-LY: Baseline Characteristics Page 14 Connolly SJ, et al. N Engl J Med 2009;361:

14 RE-LY: Primary Outcome Time to first Stroke or Systemic Embolism Page 15 Connolly SJ, et al. N Engl J Med 2009;361: Connolly SJ, et al. N Engl J Med 2010;363:

15 RE-LY: Ischaemic / Unspecified Stroke Page 16 Connolly SJ, et al. N Engl J Med 2009;361:

16 RE-LY: Hemorrhagic Stroke Page 17 Connolly SJ, et al. N Engl J Med 2009;361:

17 RE-LY: Bleeding Page 18 Connolly SJ, et al. N Engl J Med 2009;361: Connolly SJ, et al. N Engl J Med 2010;363:

18 ROCKET AF: Study Design Page 19 Am Heart J 2010;159:

19 Page 20 ROCKET AF

20 ITT Population ROCKET AF: Baseline CHADS2 Score Page 21 Patel MR, et al. N Engl J Med 2011;365:

21 ROCKET AF: Primary Efficacy End-point Page 22 Patel MR, et al. N Engl J Med 2011;365:

22 ROCKET AF: Secondary Cohort Primary Efficacy Endpoint Page 23 Eurostroke 2011

23 ROCKET AF: Bleeding events Page 24 Patel MR, et al. N Engl J Med 2011;365:

24 AVERROES: Apixaban in pts with AF Page 25 Connolly SJ, et al. N Engl J Med 2011;364:

25 AVERROES: Risk of Major Bleeding Page 26 Connolly SJ, et al. N Engl J Med 2011;364:

26 AVERROES: Results Page 27 Connolly SJ, et al. N Engl J Med 2011;364:

27 ARISTOTLE: Design Page 28 Granger CB, et al. N Engl J Med. 2011;365:

28 ARISTOTLE: Baseline Characteristics Page 29 Connolly SJ, et al. N Engl J Med 2011;364: Lopes RD, et al. Am Heart J 2010;159:

29 ARISTOTLE: Primary Outcome Stroke (Ischemic or Hemorrhagic) or Systemic Embolism Page 30 Granger CB, et al. N Engl J Med. 2011;365:

30 ARISTOTLE: Efficacy Outcomes Page 31 Granger CB, et al. N Engl J Med. 2011;365:

31 ARISTOTLE: Major Bleeding Page 32 Granger CB, et al. N Engl J Med. 2011;365:

32 Unresolved issues No established methods of monitoring No known therapeutic ranges Lack of antidotes Management of bleeding - Urgent surgery Long term safety No head to head to comparisons Patient adherence Lack of monitoring Lack of follow-up Page 33

33 Dabigatran Dyspepsia (up to 10%) Mild concentration increase in low BMI pts Numerical MI increase (NS) Warfarin protective effect: ACTIVE (W vs clopidogrel + aspirin) SPORTIF III (W vs ximelagatran) AMADEUS (W vs idraparinoux) Cautiously in pts with advanced ischemic heart disease Dabigatran etexilate appears to deteriorate when exposed to enviroment (hydrolysis) Monitoring: TT, ECT No specific antagonist Inability for Stroke t-pa thrombolysis Cautiously in pts with renal failure Page 34 J Cardiovasc Electrophysiol 2011;22:

34 Safety Updates Black box warning (Japan 8/2011) Safety Advisory (Australia 8/2011) Label Revision (FDA 9/11/2011) New Report (Boehringer 17/11/2011) EMA update on safety (10/11/2011) QuarterWatch (First Quarter 2011) Signals for dabigatran and metoclopramide From the January 12, 2012 Page 35

35 Page 36 Safety Updates

36 Acutely Injured pts on Dabigatran Prothrombin complex concentrates (PCCs) (II, VII, IX, X) (poor results) Fluids and diuresis Hemodialysis (poor results) Recombinant activated factor VII (high cost, uncertain efficacy) Page 37 Circulation. 2011;124: Time N Engl J Med 2011: 365;21.

37 Rivaroxaban Low TTR: 55% more difficult to achieve target INR in high risk patients artifact in design or trial conduction In centers with TTR 67% : Stroke and Systematic Embolism were higher 5% of pts withdrew their consent Monitoring: measuring antifactor Xa levels, PT, ETP (endogenous prothrombin potential) Antidotes: Prothrombin complex concentrates (PCCs) (II, VII, IX, X) Circulation. 2011;124: Recombinant actiavated factor VII (high cost, uncertain efficacy) Time N Engl J Med 2011: 365;21. Page 39

38 Apixaban Low TTR: 62% Swedish National Quality Registry TTR: 76% Major bleeding rate: Thromboembolism rate: 1.6%/year 3.1%/year (SNQR 2.6%/year) (SNQR1.4%/year) Antidotes: Prothrombin complex concentrates (PCCs) (II, VII, IX, X) As extrapolation by study for rivaroxaban and suggested by authors Recombinant actiavated factor VII (high cost, uncertain efficacy) Time Page 40 N Engl J Med 2012;1:366. Circulation. 2011;124:00-00.

39 ESC AF Antithrombotic Guidelines 2010 Page 41 Camm AJ, et al. Eur Heart J 2010;31:

40 Cost 6,75 / day 4,83 / day 1650 / day Page 42