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LE TRAITEMENT ANTITHROMBOTIQUE DE LA FA

LE TRAITEMENT ANTITHROMBOTIQUE DE LA FA. PROF L DE ROY UNIVERSITE DE LOUVAIN BELGIQUE. AF : STROKE AND BLEEDING EVENTS. STROKE. Rate in patients not taking warfarin, in AF 5.00 / year 1.0 - 7.0

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LE TRAITEMENT ANTITHROMBOTIQUE DE LA FA

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  1. LE TRAITEMENT ANTITHROMBOTIQUE DE LA FA PROF L DE ROY UNIVERSITE DE LOUVAIN BELGIQUE

  2. AF : STROKE AND BLEEDING EVENTS STROKE Rate in patients not taking warfarin, in AF 5.00 / year 1.0 - 7.0 Rate in patients taking warfarin, in AF 1.35 / year 0.4 - 2.3 Rate in patients not taking warfarin, in NSR 0.1 / year 0.09 - 1.0 Relative risk for patients with previous stroke 2.0* 1.0 - 3.0* Risk of death from stroke 25 8 - 35 Risk of permanent disability for survivors 50 35 - 71 MAJOR BLEEDING EVENT Rate in patients not taking warfarin, in AF 0.80 / year 0 - 1.9 Rate in patients taking warfarin, in AF 1.46 / year 0.49 - 18.0 Relative risk for patients with previous bleed 1.5* 0 - 3.0* Risk of death from major bleed 22 12.5 - 33 Risk of morbidity for survivors of major bleed 7 0 - 15 Greenberg 1998 Marcov Decision Analysis in AF * integer

  3. Patient-Years No. ofEvents Stroke Prevention in Atrial Fibrillation: Warfarin Data AFASAK 27 811 BAATAF 15 922 CAFA 14 478 SPAF 23 508 SPINAF 29 972 Combined 108 3691 100 0 50 -50 -100 Warfarin Better Warfarin Worse Atrial Fibrillation Investigators. Arch Intern Med. 1994;154:1449-1457. RR: 69% (p<.001)

  4. Stroke Prevention in Atrial Fibrillation: ASA Data Patient-Years No. ofEvents AFASAK 35 807 SPAF 65 1457 Combined 100 2264 100 0 50 -50 -100 Aspirin Better Aspirin Worse Atrial Fibrillation Investigators. Arch Intern Med. 1994;154:1449-1457. Risk Reduction, 19 %

  5. Classe I IIa IIb III A B C PREVENTION DES THROMBO-EMBOLIES CONCEPT GENERAL Antithrombotic therapy to prevent thromboembolism is recommended for ALL PATIENTS with AF, except those with lone AF or contraindications. Fuster V, Ryden LE, Cannom DS et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation. 2006 Sep;8(9):651-745.

  6. THROMBOEMBOLISM RISK FACTORS Major Risk Factors: - Valvular heart disease - Prosthetic heart valve - Prior CVA or TIA Moderate Risk Factors: - Age > 75 - HTN - Diabetes - CHF

  7. CHADS2 : évaluation du risque d’AVC chez des patients avec FA non valvulairesans anticoagulation

  8. Relation entre le score de CHADS2et le risque d’AVC * Le ratio ajusté d’AVC est dérivé d’une analyse multivariée ne comportant pas d’usage d’aspirine. Arch Intern Med 2003;163:936–43 JAMA 2001;285:2864 –70

  9. Classe I IIa IIb III A B C PREVENTION DES THROMBO-EMBOLIES ASPIRINE OU AVK ? For primary prevention of thromboembolism in patients with nonvalvular AF who have just ONEof the MODERATE validated risk factors, antithrombotic therapy with either ASPIRIN OR A VITAMIN K antagonist is reasonable,

  10. Classe I IIa IIb III A B C PREVENTION DES THROMBO-EMBOLIES INDICATION DES ANTICOAGULANTS ORAUX Anticoagulation with a vitamin K antagonist is recommended for patients with >1 MODERATE RISK FACTOR Such factors include age over 75 years or greater, hypertension, heart failure, impaired left ventricular systolic function (ejection fraction 35% or less or fractional shortening less than 25%), and diabetes mellitus.

  11. Classe I IIa IIb III A B C Prévention des thrombo-embolies FACTEURS DE RISQUE MOINS VALIDES For patients with nonvalvular AF who have one or moreof the following less well-validated risk factors, antithrombotic therapy with either ASPIRIN OR A VITAMIN K ANTAGONISTis reasonable for prevention of thromboembolism: age 65 to 74 years, female gender or coronary artery disease. The choice of agent should be based upon the risk of bleeding complications, ability to safely sustain adjusted chronic anticoagulation, and patient preferences. Fuster V, Ryden LE, Cannom DS et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation. 2006 Sep;8(9):651-745.

  12. RISQUE D’HÉMORRAGIE INTRACRANIENNE SELON L’INTENSITÉ DE L’ANTICOAGULATION 20 15 10 5 1 Odd ratio Accidents ischémiques Hémorragies intracraniennes 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 International Normalized Ratio

  13. Classe I IIa IIb III A B C PREVENTION DES THROMBO-EMBOLIES LONE AF + AVK Long-term anticoagulation with a vitamin K antagonist IS NOT RECOMMENDED for primary prevention of stroke in patients ≤ 60 years without heart disease (lone AF) or risk factors for thromboembolism. ACC/AHA/ESC Guidelines Circulation 2006

  14. Classe I IIa IIb III A B C PREVENTION DES THROMBO-EMBOLIESLONE AF + ASPIRINE In patients with AF < 60 years without heart disease or risk factors for thromboembolism (lone AF), the risk of thromboembolism is low without treatment and the effectiveness of aspirin for primary prevention of stroke relative to the risk of bleeding has not been established.

  15. STENTS + FA

  16. Classe I IIa IIb III A B C PREVENTION DES THROMBO-EMBOLIES STENTS Clopidogrelshould be given for a minimum of 1 month after implantation of a baremetal stent, at least 3 months for a sirolimus-eluting stent, at least 6 months for a paclitaxel-eluting stent and 12 months or longer in selected patients, following which warfarin may be continued as monotherapy in the absence of a subsequent coronary event. When warfarin is given in combination with clopidogrel or low-dose aspirin, the dose intensity must be carefully regulated.

  17. STENTS ANTIPLAQUETTAIRES ET AVK CONSENSUS • BMS: • AAS: à vie • CLOPIDOGREL 75 mg: 1 mois 2. DES: AAS + CLOPIDOGREL: 1 an AAS + CLOPIDOGREL: à vie (si haut risque) 3. INFARCTUS : AAS + CLOPIDOGREL: 1 an

  18. STENTS ET ANTIAGREGANTS Guidelines for PCI EurHJ 2005

  19. HEMORRAGIES MAJEURES ET TRIPLE THERAPIE Rubboli Expert consensus document Ann Med 2008

  20. QUID DES ANTIAGREGANTS?

  21. FA documentée Facteurs de risques cardio-vasculaires Facteurs influençant le choix pour ACTIVE A Eligible pour ACTIVE W : Clopidogrel (75 mg) + Aspirine (75 à 100 mg) versus Anticoagulant oral standard avec ajustement de la dose Eligible pour ACTIVE A : Clopidogrel (75 mg) + Aspirine (75 à 100 mg) versus Aspirine (75 à 100 mg) (double aveugle) ACTIVE I : Irbesartan versus Placebo (double aveugle) Follow-up : 3 ans (visites tous les 3 mois puis tous les 6 mois) ETUDE ACTIVE (BMS / Sanofi-Synthelabo)

  22. ACTIVE W Connoly Lancet 2006

  23. Hohnloser ACTIVE W JACC 2007

  24. ACTIVE + RISK FACTORS Healey ACTIVE: Risks and benefit Stroke 2008

  25. n: 6706 pts Hohnloser ACTIVE W JACC 2007

  26. The Cochrane library 2008

  27. The Cochrane library 2008

  28. Classe I IIa IIb III A B C Prévention des thrombo-embolies ASPIRINE Aspirin, 81-325 mg daily, is recommended as an alternative to vitamin K antagonists in low-risk patients or in those with contraindications to oral anticoagulation. Fuster V, Ryden LE, Cannom DS et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation. 2006 Sep;8(9):651-745.

  29. Classe I IIa IIb III A B C Prévention des thrombo-embolies VALVES MECANIQUES For patients with AF who have mechanical heart valves, the target intensity of anticoagulation should be based on the type of prosthesis maintaininga INR of at least 2.5. Fuster V, Ryden LE, Cannom DS et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation. 2006 Sep;8(9):651-745.

  30. Classe I IIa IIb III A B C Prévention des thrombo-embolies FLUTTER AURICULAIRE Antithrombotic therapy is recommended for patients with atrial flutter as for those with AF. Fuster V, Ryden LE, Cannom DS et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation. 2006 Sep;8(9):651-745.

  31. Classe I IIa IIb III A B C Prévention des thrombo-embolies AVK ET INTERVENTION A RISQUE HEMORRAGIQUE In patients with AF who do not have mechanical prosthetic heart valves, it is reasonable to interrupt anticoagulation for up to one weekwithout substituting heparin for surgical or diagnostic procedures that carry a risk of bleeding. Fuster V, Ryden LE, Cannom DS et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation. 2006 Sep;8(9):651-745.

  32. PATIENTS AGES?

  33. ELDERLY BAFTA STUDY n: 973 pts Mean age: 81.5 y

  34. Classe I IIa IIb III A B C Prévention des thrombo-embolies AVK A DOSE MODEREE? In patients 75 years of age and older at increased risk of bleeding but without frank contraindications to oral anticoagulant therapy, and in other patients with moderate risk factors for thromboembolism who are unable to safely tolerate anticoagulation at the standard intensity of INR 2.0 to 3.0, a LOWER INR TARGET OF 2.0 (range 1.6 to 2.5) may be considered for primary prevention of ischemic stroke and systemic embolism. Fuster V, Ryden LE, Cannom DS et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation. 2006 Sep;8(9):651-745.

  35. ET POUR LA CARDIOVERSION?

  36. Classe I IIa IIb III A B C Anticoagulation pour la cardioversionAVK ET FA < 48 h During the first 48 hours after onset of AF, the need for anticoagulationbefore and after cardioversion may be based on the patient’srisk of thromboembolism. Fuster V, Ryden LE, Cannom DS et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation. 2006 Sep;8(9):651-745.

  37. Classe I IIa IIb III A B C Anticoagulation pour la cardioversionCARDIOVERSION RAPIDE As an alternative to anticoagulation prior to cardioversion of AF, it is reasonable to perform transesophageal echocardiography (TEE) in search of thrombus in the left atrium or left atrial appendage. Fuster V, Ryden LE, Cannom DS et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation. 2006 Sep;8(9):651-745.

  38. Classe I IIa IIb III A B C Anticoagulation pour la cardioversionCARDIOVERSION RAPIDE For patients with no identifiable thrombus, CARDIOVERSIONis reasonableimmediatelyafter anticoagulation withUNFRACTIONATED HEPARIN (e.g., initiate by intravenous bolus injection and an infusion continued at a dose adjusted to prolong the activated partial thromboplastin time to 1.5 to 2 times the control valueuntil oral anticoagulation has been established with a vitamin K antagonist (e.g., warfarin), as evidenced by an INR ≥ 2.0.). Fuster V, Ryden LE, Cannom DS et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation. 2006 Sep;8(9):651-745.

  39. Classe I IIa IIb III A B C Anticoagulation pour la cardioversionCARDIOVERSION RAPIDE Thereafter, oral anticoagulation (INR 2.0 to 3.0)is reasonable for a total anticoagulation period of at least 4 weeks, as for patients undergoing elective cardioversion. Fuster V, Ryden LE, Cannom DS et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation. 2006 Sep;8(9):651-745.

  40. Classe I IIa IIb III A B C Anticoagulation pour la cardioversionCARDIOVERSION RAPIDE Limited data are available to support the subcutaneous administration of a low-molecular-weight heparinin this indication. Fuster V, Ryden LE, Cannom DS et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation. 2006 Sep;8(9):651-745.

  41. ACUTE II TRIAL KLEIN 2006

  42. Classe I IIa IIb III A B C Anticoagulation pour la cardioversionFLUTTER AURICULAIRE For patients with atrial flutterundergoing cardioversion, anticoagulationcan be beneficial according to the recommendations as for patients with AF. Fuster V, Ryden LE, Cannom DS et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation. 2006 Sep;8(9):651-745.

  43. Tissue factor Collagen Aspirin Plasma Clotting Cascade ADP Apixaban Rivaroxaban Clopidogrel Prasugrel AZD6140 Cangrelor Thromboxane A2 Prothrombin Conformational Activation of GPIIb/IIIa AT Idraparinux Factor Xa Thrombin Platelet Aggregation Dabigatran Ximelagatran Fibrinogen Fibrin Thrombus Targets for Antithrombotic treatment in atrial fibrillation

  44. RE-LY TRIAL 18.114 pts DABIGATRAN ETEXILATE vs WARFARINE (INR 2-3) ARISTOTLE TRIAL APIXABAN vs WARFARINE

  45. CONCLUSIONS • Un traitement antithrombotique doit toujours être envisagé chez un patient en FAP, persistante ou permanente. • Une sélection judicieuse des patients et de l’antithrombotique s’impose néanmoins . • L’abstention est parfois recommandée. • Les nouveaux anticoagulants oraux sont attendus avec impatience

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