Revisión de las nuevas guías de FA

www.escardio.org/guidelines

Gonzalo Barón Esquivias Servicio de Cardiología Hospital Universitario Virgen del Rocío Sevilla

R Thomson et al. Guidelines on anticoagulant treatment for atrial fibrillation in Great Britain: variation in content and implications for treatment.

La tasa de respuesta global fue del 66% (350/534), remitiendo 48 documentos de los que 20 cumplían los requisitos para definirlos como una guía.

La longitud oscilaban entre una única página y 28, y estaban orientadas fundamentalmente a médicos generales y a poblaciones de 12,000 a 500,000.

Cuando se aplicaron a 100 pacientes consecutivos, el número a los que se recomendaba anticoagulación en las distintas guías oscilaba entre 13 y 100 (Figura 1). A sólo un paciente todas las guías le hubieran recomendado tratamiento anticoagulante, pero a todos los pacientes se les habría recomendado anticoagulación según al menos 2 guías (no siempre las mismas).

Los valores diana del INR variaban entre 1.2 a 1.5 y 2.5 a 3.0.

BMJ 1998; 316: 509-513 www.escardio.org/guidelines

Pรกginas: 15 Referencias: 155 (Circulation. 1996;93:1262-1277.) www.escardio.org/guidelines

Pรกginas: 26 Referencias: 213

www.escardio.org/guidelines

Pรกginas: 71 Referencias: 580

www.escardio.org/guidelines

Pรกginas: 51 Referencias: 371 www.escardio.org/guidelines

www.escardio.org/guidelines

www.escardio.org/guidelines

Contributions to the Guideline

25

17

26

www.escardio.org/guidelines

www.escardio.org/guidelines

61 pages/200 references/12 figures 18 tables/210 recomendations

Recommendations Total = 210 Class of Recommendation 18%

7% 40% C las s I

35%

C las s IIa C las s IIb C las s III

Should be done Should be recomended May be recomended Level of Evidence Should be avoided 16% 51%

L oE A

33%

L oE B L oE C

www.escardio.org/guidelines

Clasification of Atrial Fibrillation First diagnosed episode of atrial fibrillation Paroxysmal (usually ≤ 48 h) Persistent (> 7 days or requires CV) Long-standing Persistent (> 1 year) Permanent (accepted)

www.escardio.org/guidelines

Importants elements in the history Does the heart rhythm during the episode feel regular or irregular?

Is there any precipitating factor such as exercise, emotion or alcohol intake?

Are symptoms during the episodes moderate or severa--the severity may be expressed using the EHRA score3, wich is similar to the CCS-SAF score41.

Are the episodes frequent or infrequent, and are they long or short lasting?

Is there a history of concomitant disease such as hypertension, coronary heart disease, heart failure, peripheral vascular disease, cerebrovascular disease, stroke, diabetes, or chronic pulmonary disease?

Is there an alcohol abuse habit?

Is there a family history of AF?

www.escardio.org/guidelines

Symptoms score Classification of AF-related symptoms (EHRA score) EHRA class

Explanation

EHRA I

‘No symptoms’

EHRA II

‘Mild symptoms’; normal daily activity not affected

EHRA III

‘Severe symptoms’; normal daily activity affected

EHRA IV

‘Disabling symptoms’; normal daily activity discontinued

www.escardio.org/guidelines

Diagnosis / Follow-up Class I recomendations Recommendations

Class

Level

Ref-

The diagnosis of AF requires documentation by ECG,

I

B

3,31

In patients with suspected AF, an attempt to record an ECG should be made when symptoms suggestive of AF occur

I

B

3,43

A simple symptom score (EHRA score) is recommended to quantify AF-related symptoms.

I

B

3,41

All patients with AF should undergo a thorough physical examination, and a cardiac-and arrhythmia-related history should be taken.

I

C

In patients with severe symptoms, docunmented or suspected heart disease, or risk factors, an echocardiogram is recommended.

I

B

In patients treated with antiarrhythmic drugs, a 12-lead ECG should be recorded at regular intervals during follow-up.

I

C

www.escardio.org/guidelines

3.23.44

Critical Questions on Follow-up ● Has the risk profile changed ( e.g. new diabetes or hypertension) especially with regards to the indication for anticoagulation? ● Has the need for anticoagulation passed, e.g. postcardioversion in a patient with low thrombo-embolic risk? ● Have the patient’s symptoms improved on therapy. If not, should other therapy be considered? ● Are there signs of proarrhythmia or risk of proarrhythmia. If so, should the dose of an anthiarrhytmic drug be reduced or a change made to another therapy? ● Has paroxysmal AF pregressed to a persistent / permanent form, in spite of antiarrhythmic drugs; in such a case, should another therapy be considered?

www.escardio.org/guidelines

The management cascade for patients with AF Atrial fibrillation

Record 12-lead ECG

Anticoagulation issues

Assess TE Risk

Rate and Rhythm control

Treatment of underlying disease ‘Upstream’ therapy

www.escardio.org/guidelines

Presentation EHRA score Associated disease Initial assessment Oral anticoagulant Aspirin None

AF type Symptoms

Consider referral

Rate control ± Rhythm control Antiarrythmic drugs Ablation ACEIs/ARBs Statins/PUFAs Others

CHA2DS2-VASc Risk factor

Risk factors for stroke and thrombo-embolism In non-valvular AF

Congestive heart failure/LV dysfunction Hypertension ‘Major’ Risk factors AGE ≥ 75 Diabetes Mellitus Previous stroke, TIA, Or systematic embolism

Stroke/TIA/thrombo-embolism Age≥75 years Vascular disease Age 65-74

Score 1

1 ‘Clinically revelant non-major’ Risk factors 2 1

Heart failure or moderate to Severe LV systolic dysfunction 2 (e.g. LV EF ≤ 40%) Hypertension – Diabetes Mellitus 1 Female sex – Age 65-74 years Vascular disease

1

Sex category (i.e. female sex)

1

Maximum score

9

www.escardio.org/guidelines

ADJUSTED STROKE RATE CHADS2 score

Patients (n= 1733)

Adjusted stroke rate (%/year) 95% confidence interval

0 1 2 3

120 463 523 337

0

1

0%

1

422

1.3%

2

1230

2.2%

3

1730

3.2%

4

1718

4.0%

5

1159

6.7%

6

679

9.8%

7

294

9.6%

8

82

6.7%

9

14

15.2%

score

4.0 (3.1 – 5.1) 5.9 (4.6 – 7.3) 8.5 (6.3 – 11.1)

5

65

12.5 (8.2 – 17.5)

www.escardio.org/guidelines

Adjusted stroke rate (%/year)

2.8 (2.0 – 3.8)

220

5

Patients (n= 7239)

1.9 (1.2 - -3.0)

4

6

CHA2DS2-VASc

18.2 (10.5 – 27.4)

CHA2DS2-VASc Thromboembolic Risk Score CHADS2 score ≥ 2†

Consider other risk factors*

No

Yes

Age ≥ 75 years No

Yes

≥ 2 other risk factors* No

Yes

† Congestive heart failure, Hypertension, Age ≥ 75 years Diabetes Stroke/TIA/thrombo-embolism (doubled) *Other clinically relevant Non-major risk factors: Age 65-74, female sex, Vascular disease

OAC

1 other risk factor* Yes

OAC (or aspirin) Nothing (or aspirin)

No www.escardio.org/guidelines

Selected OAC recommendations Recommendations

Class

Level

Ref-

Antithrombotic therapy to prevent thrombo-embolism is recommended for all patients with AF, except in those at low risk (lone AF, aged < 65 years, or with contraindications).

I

A

47,48,63

It is recommended that the selection of the antithrombotic therapy should be based upon the absolute risk of stroke/thrombo-embolism and bleeding, and the relative risk and benefit for a given patient.

I

A

47,48,50

The CHADS2 [cardiac failure, hypertension, age, diabetes, stroke (doubled)] score is recommended as a simple initial (easily remembered) means of assessing stroke in non-valvular AF.

I

A

50

I

A

47,48,54

I

A

52

* For the patients with a CHADS score of ≥2, chronic OAC therapy with a VKA is recommended in a doseadjusted regimen to achieve an INR range of 2,0-3,0 (target 2,5), unless contraindicated.

For a more detailed or comprehensive stroke assessment in AF (e.g. With CHADS score 0-1), a risk factor-based approach is recommended, considering ‘major? And ‘clinically non-major’ risk factors.

In patients with no risk factors who are at low risk (essentially patients < 65 years wich lone AF, with none of the risk factors), no antithrombotic therapy should be considered, rather than aspirin.

Combination therapy with aspirin 75-100 mg plus clopidogrel 75 mg daily, should be considered for stroke prevention in patients for whom there is patient refusal to take OAC therapy or a clear contraindication to OAC therapy (e.g. inability to cope or continue with anticoagulation monitoring), where there is a low risk of bleeding.

www.escardio.org/guidelines

IIa

IIa

B

47,48

B

58

Bleeding Risk -- HAS-BLED Score Letter

Clinical characteristic

Points awarded

H

Hypertension

A

Abnormal renal and liver function (1 point each)

S

Stroke

1

B

Bleeding

1

L

Labile INRs

1

E

Elderly (e.g. age >65 years)

1

D

Drugs or alcohol (1 point each)

1 1 or 2

1 or 2 Maximun 9 points

www.escardio.org/guidelines

Phase III trials comparing new anticoagulants in AF 1. Versus Warfarin Direct Thrombin inhibition: Ximelagatran (Sportif III & V) - 2003, 2005 Dabigatran (RELY) 2009 Direct factor Xa inhibition: Ribaroxaban (ROCKET) – Nov 2010 Apixaban (ARISTOTELE) – Aug 2011 Edoxaban (ENGAGE AF – TIMI48) – 2012?

Betrixaban (start phase III2011?) – 2014?

2. Versus Aspirin: Apixaban (AVERROES) Aug 2010

www.escardio.org/guidelines

Rate and Rhythm Control Appropriate antithrombotic therapy Clinical evaluation

Paroxysmal

Permanent

Persistent Long-standing persistent

Rhythm control

Remains symptomatic

Failure of rhythm control

www.escardio.org/guidelines

Rate control

Optimal Rate Control RATE CONTROL No or tolerable symptoms

Symptoms

Accept lenient rate control

More strict rate control

It is reasonable to initiate treatment with a lenient rate control protocol aimed at a resting heart rate < 110 bpm.

It is reasonable to adopt a stricter rate control strategy when symptoms persist or tachycardiomyopathy occurs, despite lenient rate control resting heart rate < 80 bpm and heart rate during moderate exercise < 110 bpm. After achieving the strict heart rate target, a 24 h Holter monitor is recommended to assess safety.

IIa

IIa

www.escardio.org/guidelines

B

B

98

98

Exercise test if excessive Heart rate is anticipated During exerciseNo

24 h ECG for safety

In patients who experience symptoms related to AF during activity, the adequacy of rate control should be assessed during exercise, and therapy should be adjusted to achieve a physiological chronotropic response and to avoid bradycardia

I

C

Optimal Rate Control It is reasonable to initiate treatment with a lenient rate control protocol aimed at a resting heart rate < 110 bpm.

IIa

B

98

It is reasonable to adopt a stricter rate control strategy when symptoms persist or tachycardiomyopathy occurs, despite lenient rate control resting heart rate < 80 bpm and heart rate during moderate exercise < 110 bpm. After achieving the strict heart rate target, a 24 h Holter monitor is recommended to assess safety.

IIa

B

98

www.escardio.org/guidelines

Atrial fibrillation Inactive lifestyle

Choice of Rate Control Medication

Active lifestyle Associated disease

None or hypertension

Digitalis

www.escardio.org/guidelines

β-blocker Diltiazem Verapamil Digitalis

Heart failure

β-blocker Digitalis

COPD

Diltiazem Verapamil Digitalis β1-selective blockers

Principles of Antiarrhythmic Drug Therapy to Mantain Sinus Rhythm 1. Treatment is motivated by attempts to reduce AF-related symptoms.

2. Efficacy of antiarrhythmic drugs to mantain sinus rhythm is modest.

3. Clinically successful antiarrhythmic drug therapy may reduce rather than eliminate recurrence of AF. 4. If one antiarrhythmic drug â&#x20AC;&#x2DC;failsâ&#x20AC;&#x2122; a clinically acceptable response may be to achieved with another agent.

5. Drug-induced proarrhythmia or extra-cardiac side-effects are frequent 6. Safety rather than efficacy considerations should primarily guide the choice of antiarrhythmic agent

www.escardio.org/guidelines

Antiarrhythmic medication for Rhythm Control

The following antiarrhythmic drugs are recomended for rhythm control in patients with AF, depending on underlying heart disease:

www.escardio.org/guidelines

* amiodarone

I

A

46,111,125

* dronedarone

I

A

95.99

* flecainide

I

A

111, 127

* propafenone

I

A

111, 125

* d, l-sotalol

I

A

46, 83, 111

Drugs and doses for pharmacolgical conversion of (recent onset) AF Drug

Dose

Follow-up dose

Amiodarone

5 mg/kg i.v. over 1 h.

30 mg/h

Flecainide

2 mg/kg over 10 min or 200-300 mg p.o.

N/A

Ibutilide

1 mg i.v. over 10 min

1 mg i.v. over 10 min after waiting for 10 min

Propafenone

2 mg/kg i.v. over 10 min or 450-600 mg p.o.

Vernakalant

3 mg/kg i.v. over 10 min

Second infusion of 2 mg/kg i.v. over 10 min after 15 min rest.

The CHMP (Committee for Medicine Products for Human Use) under EMA has recommended approval of Vernakalant

www.escardio.org/guidelines

Antiarrhythmic medication for Rhythm Control

Amiodarone is more effective in maintaining sinus rhythm than sotalol, propafenone, flecainide (by analogy), or dronedarone (loE A), but because of its toxicity profile should generally be used when other agents have failed or are contraindicated (LoE C)

I

In patients with severe heart failure, NYHA class III and IV or recently unstable (decompensation within the prior month) NYHA class II, amiodarone should be of choice

I

www.escardio.org/guidelines

A

C

46, 111 121, 125

B 126

Antiarrhythmic medication for Rhythm Control Dronedarone should be considered in order to reduce cardiovascular hospitalizations in patients with non-permanent AF and cardiovascular risk factors.

Dronedarone is not recommended for treatment of AF in patients with NYHA class III an IV, or with recently unstable (decompensation within the prior month) NYHA class II heart failure.

www.escardio.org/guidelines

IIa

B

95,99

III

B

117,122

Choice of AAD – Underlying pathology Minimal or no heart disease

Significant underlying heart disease

? Prevention of remodeling ACEIs/ARB/statin β blockade where appropriate

Treatment of underlying condition and ? Prevention/reversal Of remodeling – ACEI/ARB/statin. β blockade where appropriate HT

No LVH

LVH

Dronedarone / Flecainide / Propafenone / Sotalol

Dronedarone

Amiodarone

Amiodarone

www.escardio.org/guidelines

CHF

CAD

Stable NYHA I/II

Dronedarone Sotalol

Dronedarone

Amiodarone

NYHA III/IV or ‘unstable’ NYHA II

New indications for AAD in AF 1. Previous anti-arrhythmic drugs did not demonstrate an impact on serious cardiovascular outcomes in AF patients.

2. Dronedarone alter this concept as it reduces cardiovascular outcomes.

- CV hospitalization or all-causes death (24% reduction) - CV mortality (28% reduction) - Arrhythmic death (45% reduction) - Stroke (34% reduction) 3. Dronedarone has low-risk of pro-arrhythmia or extra-cardiac toxicity and a favourable tolerability.

www.escardio.org/guidelines

(%)

CV Morbidity-Mortality Outcome Studies

40 35 30 25

25

Morbidity-mortality Relative Risk Reduction

20 15

11

8

10

37

13,2

16

20

20

EUROPA

CURE

22

24

5 0 ATHENA

(%) 8

ACCLAIM

FIELD HELSINKI

Val-HeFT

CHARM

HOPE

LIPID

CARDS

7,5

7

Morbidity-mortality Absolute Risk Reduction

6 5 4 3 2

1,9

1,9

2,1

EUROPA

LIPID

CURE

3

3,2

3,3

ACCLAIM

CARDS

Val-HeFT

3,8

4,3

1

1 0 ATHENA

FIELD HELSINKI

www.escardio.org/guidelines

HOPE

CHARM

Catheter Ablation for Atrial Fibrillation

Ablation of common atrial flutter is recommended as a part of an AF ablation procedure if documented prior to the ablation procedure or occurring during the AF ablation

www.escardio.org/guidelines

I

B

126

Indication for LA Catheter Ablation Catheter ablation for paroxysmal AF should be considered in symptomatic patients who have previously failed a trial of antiarrhythmic medication Ablation of persistent symptomatic AF that is refractory to antiarrhythmic therapy should be considered a treatment option

Catheter ablation of AF may be considered prior to antiarrhythmic drug therapy in symptomatic patients despite adequate rate control with paroxysmal symptomatic AF and no significant underlying heart disease

IIa

A

96, 131, 132,133, 135,137, 138

No or minimal heart disease (including HT without LVH) Paroxysmal AF

IIa

IIb

B

B

Persistent AF

33

131

Catheter Ablation for AF

Dronedarone Flecainide Propafenone Sotalol

Amiodarone www.escardio.org/guidelines

Ablation when SCD is present

Relevant underlying heart disease

CHF Catheter ablation of AF in patients with heart failure may be considered when antiarrhythmic medication, incluiding amiodarone, fails to control symptoms

Catheter ablation of AF may be considered in patients with symptomatic long-standing persistent AF refractory to antiarrhythmiuc drugs.

IIb

IIb

B

C

131

NYHA III/IV or â&#x20AC;&#x2DC;unstableâ&#x20AC;&#x2122; NYHA II

Hypertension with LVH

Stable NYHA I/II

Dronedarone

Amiodarone

www.escardio.org/guidelines

CAD

Dronedarone Sotalol

Dronedarone

Catheter Ablation for AF

When should AF ablation be considered?

As early as possible Emerging indication: AF ablation as first-line treatmentâ&#x20AC;Ś www.escardio.org/guidelines

â&#x20AC;&#x153;Upstreamâ&#x20AC;? Therapy Primary Prevention ACE Inhibitors, Angiotensin receptors blockers, Aldosterone Antagonists, Statins, PUFAs.

Agents considered:

ACEIs and ARBs should be considered for prevention of new- onset AF in patients with heart failure and reduced ejection fraction ACEIs and ARBs should be consi- dered for prevemntion of new-onset AF in patients with hypertension, particularly with left ventricular hypertrophy Statins should be considered for prevention of new-onset AF after coronary artery bypass grafting, isolated or in combination with valvular interventions

www.escardio.org/guidelines

IIa

IIa

A

B

145-149

Statins may be considered for pre- vention of new-onset AF in patients with underlying heart disease, particularly heart failure

147,150

Ablation of persistent symptomatic AF that is refractory to antiarrhytmic therapy should be considered a treatment option

151

IIa

B

161,162

IIa

B

III

C

164,165

â&#x20AC;&#x153;Upstreamâ&#x20AC;? Therapy Secondary Prevention Pre-treatment with ACEIs and ARBs may be considered in patients with recurrent AF and receiving antiarrhythmic drug therapy ARBs or ACEIs may be useful for prevention of recurrent paroxysmal AF or in patients with persistent AF undergoing electrical cardioversion in the absence of significant structural heart disease if these agents are indicated for other reasons (e.g. Hypertension)

www.escardio.org/guidelines

IIb

B

145-147 152-153

IIa

B

161,162

Atrial Fibrillation in Athletes

When a â&#x20AC;&#x2DC;pill-in-pocketâ&#x20AC;&#x2122; approach with sodium channel blockers is used, sport cessation should be considered for as long as the arrhythmia persists, and until 12 half-lives of the antiarrhythmic drug used have elapsed.

IIa

Isthmus ablation should be considered in competitive or leisure- time athletes with documented atrial flutter, especially when therapy with flecainide or propafenone is intended

IIa

Where appropiate AF ablation should be considered to prevent recurrent AF in athletes

IIa

www.escardio.org/guidelines

C

C

C

When a specific cause for AF is identified in an athelete (such as hyperthyroidism), it is not recommended to continue participation in competitive or leisure time sports until correction of the cause.

It is not recomended to allow physical sports activity when symtomps due to haemodynamic impairment (such as dizziness) are present

III

C

III

C

You can please all the people some of the time, and some of the people all the time, but you cannot please all the people all the time > 2000 emails from Chairman and > 3000 emails to Chairman www.escardio.org/guidelines

Muchas gracias www.escardio.org/guidelines