Transcript Traitement antithrombotique de la FA - CCN

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
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
* integer
Greenberg 1998
Marcov Decision Analysis in AF
Stroke Prevention
in Atrial Fibrillation:
Warfarin Data
No. of
Events
PatientYears
AFASAK
27
811
BAATAF
15
922
CAFA
14
478
SPAF
23
508
SPINAF
29
972
Combined 108
3691
100
50
Warfarin Better
0
-50
-100
Warfarin Worse
Atrial Fibrillation Investigators.
Arch Intern Med. 1994;154:1449-1457.
RR: 69% (p<.001)
Stroke Prevention
in Atrial Fibrillation:
ASA Data
No. of
Events
PatientYears
AFASAK
35
807
SPAF
65
1457
Combined 100
2264
100
Atrial Fibrillation Investigators.
Arch Intern Med. 1994;154:1449-1457.
50
Aspirin Better
0
-50
Aspirin Worse
Risk Reduction, 19 %
-100
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.
I
Classe
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
THROMBOEMBOLISM RISK FACTORS
Major Risk Factors:
- Valvular heart disease
- Prosthetic heart valve
- Prior CVA or TIA
Moderate Risk Factors:
- Age > 75
- HTN
- Diabetes
- CHF
CHADS2 : évaluation du risque d’AVC
chez des patients avec FA non valvulaire
sans anticoagulation
Critères de risque CHADS2
Score
AVC ou AIT
2
Age > 75 ans
1
Hypertension
1
Diabète
1
Insuffisance cardiaque
1
Relation entre le score de CHADS2
et le risque d’AVC
Patients
(N=1733)
Risque ajusté d’AVC
Ratio (% / an)* (IC 95%)
Score
CHADS2
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.
JAMA 2001;285:2864 –70
Arch Intern Med 2003;163:936–43
PREVENTION DES THROMBO-EMBOLIES
ASPIRINE OU AVK ?
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,
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A
B
C
Classe
IIa IIb III
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.
Classe
I
A
B
C
IIa IIb III
Prévention des thrombo-embolies
FACTEURS DE RISQUE MOINS VALIDES
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.
I
Classe
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.
RISQUE D’HÉMORRAGIE INTRACRANIENNE SELON
L’INTENSITÉ DE L’ANTICOAGULATION
Odd ratio
20
Accidents ischémiques
15
Hémorragies intracraniennes
10
5
1
1.0
2.0
3.0
4.0
5.0
International Normalized Ratio
6.0
7.0
8.0
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.
Classe
I
IIa IIb III
A
B
C
ACC/AHA/ESC Guidelines Circulation 2006
PREVENTION DES THROMBO-EMBOLIES
LONE 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.
Classe
I
A
B
C
IIa IIb III
STENTS + FA
PREVENTION DES THROMBO-EMBOLIES
STENTS
Clopidogrel should be given for a minimum of 1 month after
implantation of a bare metal stent, at least 3 months for a sirolimuseluting 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.
I
A
B
C
Classe
IIa IIb III
STENTS ANTIPLAQUETTAIRES ET AVK
CONSENSUS
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
HEMORRAGIES MAJEURES ET TRIPLE THERAPIE
Rubboli Expert consensus document Ann Med 2008
QUID DES ANTIAGREGANTS?
ETUDE ACTIVE
(BMS / Sanofi-Synthelabo)
FA documentée
Facteurs de risques cardio-vasculaires
Facteurs influençant le choix
pour ACTIVE A
Eligible pour ACTIVE W :
Eligible pour ACTIVE A :
Clopidogrel (75 mg) + Aspirine (75 à 100 mg)
versus
Anticoagulant oral standard
avec ajustement de la dose
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)
ACTIVE W
Connoly Lancet 2006
Hohnloser ACTIVE W JACC 2007
ACTIVE + RISK FACTORS
Healey ACTIVE: Risks and benefit
Stroke 2008
n: 6706 pts
Hohnloser ACTIVE W JACC 2007
The Cochrane library 2008
The Cochrane library 2008
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.
I
Classe
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
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.
I
A
B
C
Classe
IIa IIb III
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
Antithrombotic therapy is recommended for patients with
atrial flutter as for those with AF.
I
Classe
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
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.
I
Classe
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.
PATIENTS AGES?
ELDERLY
BAFTA STUDY
n: 973 pts
Mean age: 81.5 y
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.
I
Classe
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.
ET POUR LA CARDIOVERSION?
Anticoagulation pour la cardioversion
AVK ET FA < 48 h
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.
I
Classe
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 cardioversion
CARDIOVERSION 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.
I
Classe
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 cardioversion
CARDIOVERSION 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.).
I
Classe
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 cardioversion
CARDIOVERSION 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.
I
Classe
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 cardioversion
CARDIOVERSION RAPIDE
Limited data are available to support the subcutaneous
administration of a low-molecular-weight heparin
in this indication.
I
Classe
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.
ACUTE II TRIAL KLEIN 2006
Anticoagulation pour la cardioversion
FLUTTER AURICULAIRE
For patients with atrial flutter undergoing cardioversion,
anticoagulation can be beneficial according to the
recommendations as for patients with AF.
I
Classe
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.
Targets for Antithrombotic treatment in atrial fibrillation
Tissue factor
Collagen
Aspirin
Plasma Clotting
Cascade
Apixaban
Rivaroxaban
ADP
Thromboxane A2
Prothrombin
Idraparinux
AT
Clopidogrel
Prasugrel
AZD6140
Cangrelor
Conformational
Activation of GPIIb/IIIa
Factor Xa
Thrombin
Platelet Aggregation
Dabigatran
Ximelagatran
Fibrinogen
Fibrin
Thrombus
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