LA GESTIONE DEL PAZIENTE LA GESTIONE DEL PAZIENTE CON FIBRILLAZIONE ATRIALE

Convegno Associazione G. Dossetti g“Le Malattie Cardiovascolari : dalla Fase Acuta alla

Prevenzione, l’Accesso alle Terapie nell’Era pdel Risanamento Economico”

Roma, 4 Ottobre 2011

Giuseppe Di Pasquale Unità Operativa di CardiologiaOspedale Maggiore, Bologna

www.escardio.org/guidelines

www.escardio.org/guidelines

1

CHADS2 ScoreCHADS2 Score

Risk Factor SCORE

CHF / LV dysfunction 1CHF / LV dysfunction 1

Hypertension 1Hypertension 1

Age > 75 years 1g y

Diabetes mellitus 1

Stroke / TIA 2

Gage BF et al. JAMA 2001; 285: 2864-70

CHADSCHADS22 Score: Validation for Predicting StrokeScore: Validation for Predicting Stroke

US National Registry of AFUS National Registry of AF - AFI schemeCHADS index

18.21820

%

N= 1733 pts (65-95 yrs)- SPAF scheme

CHADS2 index

12.512141618

ke R

ate

5 9

8.58

1012

ed S

trok

1.9 2.84.0

5.9

246

Adjus

te

02

0 1 2 3 4 5 6(n= 120) (n= 463) (n= 523) (n= 337) (n= 220) (n= 65) (n= 5) CHADS2 Score(n= 120) (n= 463) (n= 523) (n= 337) (n= 220) (n= 65) (n= 5) CHADS2 Score

1 point: recent CHF, hypertension, age > 75 years, diabetes mellitus2 points: prior stroke or TIA Gage BF et al. JAMA 2001; 285: 2864-70

CHADSCHADS22 Score: Validation for Predicting StrokeScore: Validation for Predicting Stroke

US National Registry of AFUS National Registry of AF - AFI schemeCHADS index

18.21820

%

N= 1733 pts (65-95 yrs)- SPAF scheme

CHADS2 index

12.512141618

ke R

ate

5 9

8.58

1012

ed S

trok

1.9 2.84.0

5.9

246

Adjus

te

02

0 1 2 3 4 5 6(n= 120) (n= 463) (n= 523) (n= 337) (n= 220) (n= 65) (n= 5) CHADS2 Score(n= 120) (n= 463) (n= 523) (n= 337) (n= 220) (n= 65) (n= 5) CHADS2 Score

1 point: recent CHF, hypertension, age > 75 years, diabetes mellitus2 points: prior stroke or TIA

Gage BF et al,. JAMA 2001; 285: 2864-70

CHA2DS2 - VASc Score2 2

Risk Factor ScoreRisk Factor ScoreCongestive heart failure / LV dysfunction 1Hypertension 1Hypertension 1Age ≥ 75 y 2Diabetes mellitus 1Diabetes mellitus 1Stroke / TIA / systemic embolism 2Vascular disease Vascular disease (prior myocardial infarction, peripheral artery disease or aortic plaque) 1Age 65 74 y 1Age 65 - 74 y 1Sex category (ie female gender) 1

Lip GYH et al. Chest 2010;137(2): 263-72

CHA2DS2 - VASc Score: Validation for Predicting Stroke

The Euro Heart Survey on AF

Adjusted StrokeRate %

11,112 N = 1.084 pts (age 66±15 years)Rate %

88

10

3,93 2 3,64

6

0 0,61,6 1,9

3,2 3,6

2

4

00

0N=103

1N=162

2N=184

3N=203

4N=208

5N=95

6N=57

7N=25

8N=9

• 1 point: CHF/LV dysfunction, Hypertension, Diabetes , Vascular disease, Age 65-74 y, Sex category

• 2 points: Age ≥ 75 y, Stroke/TIA/TE Lip G et al. Chest 2010;137:263-72

www.escardio.org/guidelines

Bleeding RiskBleeding RiskBleeding RiskBleeding Risk

an assessment of bleeding risk should be … an assessment of bleeding risk should be part of the patient assessment before starting

anticoagulation…

ESC AF GUIDELINES 2010ESC AF GUIDELINES 2010

HAS-BLED Bleeding Risk Score

H 1 point HypertensionA 1 or 2 points Abnormal renal and liver functionA 1 or 2 points Abnormal renal and liver functionS 1 StrokeB 1 BleedingB 1 BleedingL 1 Labile INRsE 1 Eldery (e.g. age > 65 years)D 1 or 2 points Drugs or alcoholp g

Maximum 9 pointsPisters R et al. Chest 2010

a u 9 po ts

NET CLINICAL BENEFIT OF ORAL ANTICOAGULANT TREATMENT IN ATRIAL FIBRILLATION

Bleeding Thromboembolism

Antithrombotic Therapy for AFibStroke Risk ReductionStroke Risk Reduction

Treatment TreatmentBetter Worse

Warfarin vs.Placebo/Control 6 Trials

n = 2,900-64%

Antiplatelet drugs 8 Trials19%vs. Placebo n = 4,876-19%

100%100% 50%50% 00 -- 50%50%Hart RG et al. Ann Intern Med 2007; 146: 857

Limiti della terapia con antagonisti della Vitamina K

Risposta non prevedibile Frequentiprevedibile

La terapia con antagonisti

qaggiustamenti della

doseFinestra di

t tt t t tt antagonisti della vitamina

K presenta Numerose interazioni

alimentari

trattamento stretta(INR range 2-3)

Monitoraggioroutinario dei fattoridella coagulazione

diversi limiti che ne

rendono

Numerose interazionicon altri farmaci

Lente insorgenza/termine

Resistenza al Warfarin

rendono difficoltoso l’impiego

d’azionep g

nella pratica clinica

1. Ansell J, et al. Chest 2008;133;160S-198S; 2. Umer Ushman MH, et al. J Interv Card Electrophysiol 2008; 22:129-137; Nutescu EA, et al. Cardiol Clin 2008; 26:169-187.

Limiti della Terapia Anticoagulante Orale

Conseguenze nella FA

U i ifi ti di i ti FA i hi diU i ifi ti di i ti FA i hi di

Conseguenze nella FA

Un significativo numero di pazienti con FA a rischio distroke non riceve la TAOUn significativo numero di pazienti con FA a rischio distroke non riceve la TAO

• Underuse of OAC for high risk AF patients was found in most of the 54 studies (1998-2008) was found in most of the 54 studies (1998 2008)

• Over two third of studies of AF patients with prior stroke/TIAreported treatment levels of under 60% of eligible patients

Most studies based on CHADS score • Most studies based on CHADS2 score reported OAC treatment levels of high risk subjects below 70%

Patients with AF and prior stroke/TIA: OAC treatment levels as a proportion of patients eligible for OAC

Ogilvie IM et al. Am J Med 2010;123:638-45

Steering Committee

Giuseppe Di Pasquale (Chairman ANMCO), Giovanni Mathieu (Chairman pp q ( ), (FADOI), Francesco Chiarella, Fabrizio Colombo, Michele Gulizia,

Gualberto Gussoni, Carlo Nozzoli, Domenico Panuccio, Salvatore Pirelli, M i S h ill Gi i V M i Z i B iMarino Scherillo, Giorgio Vescovo, Massimo Zoni Berisso

Setting of the Study

360 Participating Centers360 Participating Centers7148 enrolled patients

164C di l

196Cardiology

DepartmentsCardiology ward

Internal Medicine Dept.Hospital without cardiologyHospital with cardiology wardCardiology ward

Cardiology ward and Cath LabCardiology ward with Cath Lab

Hospital with cardiology wardHospital with cardiology ward and Cath Lab (with or without CCH)and CCH CCH)

From each Center:Duration of the enrollment 4 weeks

A T AF Baseline Characteristics

Clinical SettingClinical SettingTotal

(n. 7148)Cardiology

(n. 3862)Internal Medicine

(n. 3286) p

Females, % 47.0 43.4 51.3 <.0001Age >75 years, % 56.8 44.6 71.3 <.0001Age (years) median 77 74 80Age (years), median[IQR]

77[70-83]

74[66-80]

80[74-86] <.0001

BMI >25, % 61.9 67.1 55.9 <.0001SBP (mmHg), mean±SD 130±18 130±17 130±19 0.16

A T AF Antithrombotic Treatments in

non valvular AF (4.845 pts)

OACNone Other ATT

A T AF Risk of non prescription of OAC by age

A T AF Prescription of OAC by CHADS2

p=0.024(non valvular AF, 4845 pts)

CHADSCHADS2

A T AF Prescription of OAC by CHA2DS2-VASc

p=0.012

(non valvular AF, 4845 pts)

CHA2DS2-VASc

Limiti della Terapia Anticoagulante Orale

Conseguenze nella FA

U i ifi ti di i ti FA i hi diU i ifi ti di i ti FA i hi di

Conseguenze nella FA

Un significativo numero di pazienti con FA a rischio distroke non riceve la TAOUn significativo numero di pazienti con FA a rischio distroke non riceve la TAO

L’intensità della scoagulazione è spesso al di fuori delrange terapeutico (INR 2 0 3 0)L’intensità della scoagulazione è spesso al di fuori delrange terapeutico (INR 2 0 3 0)range terapeutico (INR 2.0 – 3.0)range terapeutico (INR 2.0 – 3.0)

Anticoagulation with Anticoagulation with WarfarinWarfarinI t it Oft O t id th T t RIntensity Often Outside the Target Range

International Study of Anticoagulation Management

100

International Study of Anticoagulation Management

Ran

ge

80

100

INR<2 INR 2–3 INR >3

n Ta

rget

40

60

% T

ime

in

20

40

%

0

U S Canada France Italy Spain

Ansell J, et al. J Thromb Thrombolysis 2007; 23: 83.

U.S. Canada France Italy Spain

% di permanenza in range INR in real life in Italiain Italia

Descrizione della distribuzione delle percentuali di controllo dell’INRDescrizione della distribuzione delle percentuali di controllo dell’INR

Range INR VKAPrecedente media mediana (p25 - p75)

% INR < 2 No 33.4% 28.8% (15.4% - 47.9%)

% INR < 2 Si 25.3% 20.0% (7.7% - 36.4%)

% INR in [2,3] No 49.7% 50.0% (33.3% - 66.7%)

% INR in [2,3] Si 56.8% 58.3% (42.5% - 73.1%)% INR in [2,3] Si 56.8% 58.3% (42.5% 73.1%)

% INR> 3 No 16.9% 13.3% (0.0% - 25.0%)

% INR> 3 Si 17.9% 14.3% (4.0% - 26.7%)

31Anticoagulation control and treatment coverage in vitamin K antagonists-treated patients: in vitamin K antagonists-treated patients:

An administrative databases analysis in a large Italian population

60%

70%

,3]

30%

40%

50%

NR

in r

ange

[2,

0%

10%

20%

30%

% I

0%0-9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 80-89 >90

% Adherence with VKA treatment

Degli Esposti L et al 2011

Naive patients Established patients

Anticoagulation control and treatment coverage in vitamin K antagonists-treated patients: an administrative databases analysis in a large Italian population (L Degli Esposti et al, 20110411)

Degli Esposti L et al. 2011

The Promise of New Anticoagulants

New Anticoagulants•Coagulation • Drug

g

cascade

•Initiation •TF/VIIaTissue factor Tissue factor pathway inhibitors:pathway inhibitors:

•IXa

•IX•X NAPc2NAPc2

•Propagation

•VIIa•IXa

•Xa

Indirect: fondaparinux, Indirect: fondaparinux, idraparinuxidraparinux

•Va

•II

Direct Oral: rivaroxaban, Direct Oral: rivaroxaban, apixaban, edoxabanapixaban, edoxaban

•Thrombin activity•IIa

Direct Parenteral: Direct Parenteral: bivalirudinbivalirudinDirect Oral: ximelagatran, Direct Oral: ximelagatran,

•Fibrinogen •Fibrin dabigatran, AZD0837dabigatran, AZD0837

Atrial Fibrillation Phase 3 Study TimelinesPhase 3 Study Timelines

Rivaroxaban Edoxaban

ROCKET AFPublished

August 2011

ROCKET AFPublished

August 2011 RE-LY

P bli h d 2009RE-LY

P bli h d 2009

Dabigatran ENGAGE AF TIMI 48

Study ongoingExpected 2012

ENGAGE AF TIMI 48Study ongoingExpected 2012August 2011 August 2011 Published 2009Published 2009 Expected 2012Expected 2012

2009 2010 2011 2012

AVERROESPublished

AVERROESPublished

ARISTOTLEPublished

ARISTOTLEPublishedPublished

February 2011Published

February 2011Published

August 2011Published

August 2011

Apixaban

1

2

ESC Guidelines 2010

SCELTA DI STRATEGIE NELLA FA

CARDIOVERSIONE+

PROFILASSI AA

CARDIOVERSIONE+

PROFILASSI AA

CONTROLLO FC+

TAO

CONTROLLO FC+

TAOPROFILASSI AAPROFILASSI AA TAOTAO

Efficacia ?Efficacia ?Sicurezza ?Sicurezza ?

Q lità di it ?Q lità di it ?Qualità di vita ?Qualità di vita ?Preferenze del paziente ?Preferenze del paziente ?

A T AF Therapeutic Strategies

Total (7148 pts) Cardiology (3862 pts)

27.4%21.2%39 8%

16.6%

51 4%

39.8%

43.6%

p<.0001

51.4%

12.9%12.9%26.6%

Rh th t l

60.5%

Rhythm control

UnknownRate control Internal Medicine (3286 pts)

Decision on Rate and Rhythm Control in Patients With Persistent AFin Patients With Persistent AF

Rhythm control strategy

60

70

80

67%

Pts with AF symptomsPts without

40

50

60

53% 48%

67%

44%

AF symptoms

20

3044%

0

10

E H t S AF G AFNET Euro Heart Survey AF Eur Heart J 2006;27:3018-26

German AFNET Europace 2009;11:423-34

Rhythm control Rhythm control Left atrial catheter ablation

Catheter Ablation for AFibCatheter Ablation for AFib

LassoLassoLassoLasso

AblatAblat AblatAblat

LAO RAO

Catheter Ablation for AF

1999, 1999, Left COMPARTIMENTALIZATIONLeft COMPARTIMENTALIZATIONLeft COMPARTIMENTALIZATIONLeft COMPARTIMENTALIZATION

2000, 2000, CPVA CPVA –– OSTIAL AblationOSTIAL Ablation

2003, 2003, CPVA CPVA –– ModifiedModified

2001, 2001, CPVA CPVA –– JUNCTION Ablation JUNCTION Ablation

Underuse of Non-Pharmacological Treatment

Adherence to Guidelines for AF ManagementThe SITAF StudyThe SITAF Study

Bottoni N et al. Europace 2010;12:1070-77

1

2

3

ESC Guidelines 2010

To evaluate whether in patients withTo evaluate whether in patients with previous AF episodes treated with

the best recommended therapies the addition of valsartan can prevent AFaddition of valsartan can prevent AF

recurrence

Time to first recurrence of AF(n 1442)(n. 1442)

Valsartan: 371/722 (51.4%)Placebo: 375/720 (52.1%)

Adjusted* HR 0.9996%CI 0.85-1.15P value 0 84P value 0.84

* The 96%CI was calculated by Cox proportional hazards model adjusted for ACE-I, amiodarone use, cardioversion, PAD, CAD

27 Settembre 2011, Ore 11.00Sala Caduti di Nassirya

Senato della RepubblicaPiazza Madama 11 RomaPiazza Madama, 11 Roma