LE TRAITEMENT ANTITHROMBOTIQUE DE LA FA

PROF L DE ROY UNIVERSITE DE LOUVAIN

BELGIQUE

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

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

MAJOR BLEEDING EVENT

* integerGreenberg 1998Marcov Decision Analysis in AF

AF : STROKE AND BLEEDING EVENTS

Stroke Prevention in Atrial Fibrillation: Warfarin Data

Warfarin BetterWarfarin Worse

Combined 108 3691

SPINAF 29 972

SPAF 23 508

CAFA 14 478

BAATAF 15 922

AFASAK 27 811

No. ofEvents

Patient-Years

100 50 0 -50 -100

Atrial Fibrillation Investigators. Arch Intern Med. 1994;154:1449-1457. RR: 69% (p<.001)

Stroke Prevention in Atrial Fibrillation: ASA Data

Atrial Fibrillation Investigators. Arch Intern Med. 1994;154:1449-1457.

Aspirin Better Aspirin Worse

Risk Reduction, 19 %

Combined 100 2264

SPAF 65 1457

AFASAK 35 807

No. ofEvents

Patient-Years

100 50 0 -50 -100

Antithrombotic therapy to prevent thromboembolism is recommended for ALL PATIENTS with AF,

except those with lone AF or contraindications.

Classe

I IIa IIb III

A

B

C

PREVENTION DES THROMBO-EMBOLIES CONCEPT GENERAL

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.

THROMBOEMBOLISM RISK FACTORSTHROMBOEMBOLISM RISK FACTORS

Major Risk Factors: - Valvular heart disease- Prosthetic heart valve- Prior CVA or TIA

Moderate Risk Factors:- Age > 75- HTN- Diabetes- CHF

Critères de risque CHADS2 Score

AVC ou AIT 2

Age > 75 ans 1

Hypertension 1

Diabète 1

Insuffisance cardiaque 1

CHADS2 : évaluation du risque d’AVC chez des patients avec FA non valvulaire

sans anticoagulation

Patients(N=1733)

Risque ajusté d’AVCRatio (% / an)* (IC 95%)

ScoreCHADS2

120 1,9 (1,2 à 3,0) 0

463 2,8 (2,0 à 3,8) 1

523 4,0 (3,1 à 5,1) 2

337 5,9 (4,6 à 7,3) 3

220 8,5 (6,3 à 17,5) 4

65 12,5 (8,2 à 17,5) 5

5 18,2 (10,5 à 27,4) 6

* Le ratio ajusté d’AVC est dérivé d’une analyse multivariée ne comportant pas d’usage d’aspirine.

Relation entre le score de CHADS2et le risque d’AVC

Arch Intern Med 2003;163:936–43JAMA 2001;285:2864 –70

For primary prevention of thromboembolism in patients with nonvalvular AF who have just

ONE of the MODERATE validated risk factors,

antithrombotic therapy with either ASPIRIN OR A VITAMIN K antagonist is reasonable,

Classe

I IIa IIb III

A

B

C

PREVENTION DES THROMBO-EMBOLIES ASPIRINE OU AVK ?

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.

Classe

I IIa IIb III

A

B

C

PREVENTION DES THROMBO-EMBOLIES INDICATION DES ANTICOAGULANTS ORAUX

For patients with nonvalvular AF who have one or more of the following less well-validated risk factors, antithrombotic therapy with either ASPIRIN OR A VITAMIN K ANTAGONIST is 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.

Classe

I IIa IIb III

A

B

C 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.

Prévention des thrombo-embolies FACTEURS DE RISQUE MOINS VALIDES

1.0

Odd ratio

Accidents ischémiques

Hémorragies intracraniennes

20

15

10

5

1

2.0 3.0 4.0 5.0 6.0 7.0 8.0

International Normalized Ratio

RISQUE D’HÉMORRAGIE INTRACRANIENNE SELON L’INTENSITÉ DE L’ANTICOAGULATION

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.

Classe

I IIa IIb III

A

B

C

PREVENTION DES THROMBO-EMBOLIES LONE AF + AVK

ACC/AHA/ESC Guidelines Circulation 2006

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.

Classe

I IIa IIb III

A

B

C

PREVENTION DES THROMBO-EMBOLIES LONE AF + ASPIRINE

STENTS + FA

Clopidogrel should be given for a minimum of 1 month after implantation of a bare metal 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.

Classe

I IIa IIb III

A

B

C

PREVENTION DES THROMBO-EMBOLIES STENTS

STENTS ANTIPLAQUETTAIRES ET AVKCONSENSUS

1.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

STENTS ET ANTIAGREGANTS

Guidelines for PCI EurHJ 2005

Rubboli Expert consensus document Ann Med 2008

HEMORRAGIES MAJEURES ET TRIPLE THERAPIE

QUID DES ANTIAGREGANTS?

ETUDE ACTIVE(BMS / Sanofi-Synthelabo)

FA documentéeFacteurs de risques cardio-vasculaires

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)

Facteurs influençant le choix pour ACTIVE A

Connoly Lancet 2006

ACTIVE W

Hohnloser ACTIVE W JACC 2007

Healey ACTIVE: Risks and benefit Stroke 2008

ACTIVE + RISK FACTORS

Hohnloser ACTIVE W JACC 2007

n: 6706 pts

The Cochrane library 2008

The Cochrane library 2008

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.

Classe

I IIa IIb III

A

B

C

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.

Prévention des thrombo-embolies ASPIRINE

For patients with AF who have mechanical heart valves, the target intensity of anticoagulation should be based on the type of prosthesis maintaining a INR of at least 2.5.

Classe

I IIa IIb III

A

B

C

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.

Prévention des thrombo-embolies VALVES MECANIQUES

Antithrombotic therapy is recommended for patients with atrial flutter as for those with AF.

Classe

I IIa IIb III

A

B

C 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.

Prévention des thrombo-embolies FLUTTER AURICULAIRE

In patients with AF who do not have mechanical prosthetic heart valves, it is reasonable to interrupt anticoagulation for up to one week without substituting heparin for surgical or diagnostic procedures that carry a risk of bleeding.

Classe

I IIa IIb III

A

B

C 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.

Prévention des thrombo-embolies AVK ET INTERVENTION A RISQUE HEMORRAGIQUE

PATIENTS AGES?

n: 973 ptsMean age: 81.5 y

BAFTA STUDY

ELDERLY

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.

Classe

I IIa IIb III

A

B

C 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.

Prévention des thrombo-embolies AVK A DOSE MODEREE?

ET POUR LA CARDIOVERSION?

During the first 48 hours after onset of AF, the need for anticoagulation before and after cardioversion may be based on the patient’s risk of thromboembolism.

Classe

I IIa IIb III

A

B

C 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.

Anticoagulation pour la cardioversionAVK ET FA < 48 h

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.

Classe

I IIa IIb III

A

B

C 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.

Anticoagulation pour la cardioversionCARDIOVERSION RAPIDE

For patients with no identifiable thrombus, CARDIOVERSION is reasonable immediately after anticoagulation with UNFRACTIONATED 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 value until oral anticoagulation has been established with a vitamin K antagonist (e.g., warfarin), as evidenced by an INR ≥ 2.0.).

Classe

I IIa IIb III

A

B

C 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.

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.

Classe

I IIa IIb III

A

B

C 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.

Anticoagulation pour la cardioversionCARDIOVERSION RAPIDE

Limited data are available to support the subcutaneous administration of a low-molecular-weight heparin in this indication.

Classe

I IIa IIb III

A

B

C 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.

Anticoagulation pour la cardioversionCARDIOVERSION RAPIDE

ACUTE II TRIAL KLEIN 2006

For patients with atrial flutter undergoing cardioversion, anticoagulation can be beneficial according to the recommendations as for patients with AF.

Classe

I IIa IIb III

A

B

C 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.

Anticoagulation pour la cardioversionFLUTTER AURICULAIRE

Targets for Antithrombotic treatment in atrial fibrillation

Tissue factor

Plasma Clotting Cascade

Prothrombin

Factor Xa

Thrombin

Fibrinogen

Collagen

ADP

Thromboxane A2

Conformational Activation of GPIIb/IIIa

Platelet Aggregation

Thrombus

Fibrin

ApixabanApixabanRivaroxabanRivaroxaban

IdraparinuxIdraparinuxAT

DabigatranDabigatranXimelagatranXimelagatran

AspirinAspirin

ClopidogrelClopidogrelPrasugrelPrasugrelAZD6140AZD6140CangrelorCangrelor

RE-LY TRIAL

18.114 pts

DABIGATRAN ETEXILATE vs WARFARINE (INR 2-3)

ARISTOTLE TRIAL

APIXABAN vs WARFARINE

CONCLUSIONS

1. Un traitement antithrombotique doit toujours être envisagé chez un patient en FAP, persistante ou permanente.

2. Une sélection judicieuse des patients et de l’antithrombotique s’impose néanmoins .

3. L’abstention est parfois recommandée.

4. Les nouveaux anticoagulants oraux sont attendus avec impatience