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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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slide1

LE TRAITEMENT ANTITHROMBOTIQUE DE LA FA

PROF L DE ROY

UNIVERSITE DE LOUVAIN

BELGIQUE

slide2

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

stroke prevention in atrial fibrillation warfarin data

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)

stroke prevention in atrial fibrillation asa data
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 %

slide5

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.

slide6

THROMBOEMBOLISM RISK FACTORS

Major Risk Factors:

- Valvular heart disease

- Prosthetic heart valve

- Prior CVA or TIA

Moderate Risk Factors:

- Age > 75

- HTN

- Diabetes

- CHF

slide7

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

slide8

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

slide9

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,

slide10

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.

slide11

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.

slide12

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

prevention des thrombo embolies lone af avk

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

prevention des thrombo embolies lone af aspirine

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.

slide16

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.

slide17

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

slide18

STENTS ET ANTIAGREGANTS

Guidelines for PCI EurHJ 2005

slide19

HEMORRAGIES MAJEURES ET TRIPLE THERAPIE

Rubboli Expert consensus document Ann Med 2008

slide21

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)

slide22

ACTIVE W

Connoly Lancet 2006

slide24

ACTIVE + RISK FACTORS

Healey ACTIVE: Risks and benefit Stroke 2008

slide25

n: 6706 pts

Hohnloser ACTIVE W JACC 2007

slide28

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.

slide29

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.

slide30

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.

slide31

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.

slide33

ELDERLY

BAFTA STUDY

n: 973 pts

Mean age: 81.5 y

slide34

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.

slide36

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.

slide37

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.

slide38

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.

slide39

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.

slide40

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.

slide42

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.

slide43

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

slide44

RE-LY TRIAL

18.114 pts

DABIGATRAN ETEXILATE vs WARFARINE (INR 2-3)

ARISTOTLE TRIAL

APIXABAN vs WARFARINE

slide45

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