ACC/ AHA/ ESC 2006 Guidelines for the Management of Patients

With Atrial Fibrillation

[JACC 2006; 48(4) : e 149 246] :

NEWLY DISCOVERED AF
______________________________________________
PAROXYSMAL

No therapy needed unless significant

Symptoms (e.g. hypotension, HF,
Angina pectoris)

PERSISTENT

Accept permanent AF

Rate control and

anticoaculation as needed

Anticoagulation and
rate control as needed
Anticoagulation as
Needed

Consider antiarrythmic
drug therapy
Cardioversion

Longterm antiarrythmic
Drug therapy unnecessary

Figure 1. Pharmacological management of patients with

newly discovered atrial fibrillation

Reccurent Paroxysmal AF
Minimal or no
Symptoms

Disabling
symptoms in AF

Anticoagulation
and rate control as needed

Anticoagulation
and rate control

Antiarrythmia
Drug therapy

AF ablation if
antiarrythmia
Treatment fails
Figure 2. Pharmacologic management of patients
with reccurent paroxysmal atrial fibrillation.

Reccurent Persistent AF
Minimal or no
symptoms
Anticoagulation
and rate control as
needed

Disabling
symtomps in AF

Permanent AF
Anticoagulation
control as needed

Anticoagulation
and rate control
Antiarrythmia
drug therapy
Electrical
cardioversion as
needed

Continue anticoagulation as
needed and therapy to
maintain sinus rhythm
Consider ablation for severely
symtomatic reccurent AF
after failure of greater than or
equal to 1 antiarrythmic drug
plus rate control

Figure 3. Pharmacological management of patients with reccurent persistent or permanent atrial

fibrillation. Initiate drug therapy before cardioversion to reduce the likelihood of early reccurent
of atrial fibrillation.

Table 1. Intravenous and Orally Administered Pharmacological Agents for

Heart Rate Control in Patients With AF
Drug

Class/
Evidence

Loading Dose

Onset

Maintenance Dose

Major Side Effects

ACUTE SETTING
HEART RATE CONTROL IN PATIENTS WITHOUT ACCESSORY PATHWAY
Esmolol

I/C

500 mcg/kg IV over 1 min

5 min

60-200 mcg/kg/min IV

BP,HB,HR,asthma,HF

Metoprolol

I/C

5 min

NA

BP,HB,HR,asthma,HF

Propanolol
Diltiazem
Verapamil

I/C
I/B
I/B

2,5-5 mg iv bolus over 2 min;up to

3 doses
0,15 mg/kg IV
0,25 mg/kg iv over 2 min
0,075-0,15 mg/kg IV over 2 min

2-7 min
3-5 min

NA
5-15 mg/h IV
NA

BP,HB, HR, asthma, HF

BP, HB, HF
BP, HB, HF

0,5-1 mg/min IV

BP,HB,
Pulmonary
toxicity,skin
discoloration,
hypothyroidism,
hyperthyroidism,
corneal
deposits, optic neuropathy,
warfarin interaction, sinus
bradycardia

HEART RATE CONTROL IN PATIEN WITH ACCESSORY PATHWAY

Amiodarone
IIa/C
150 mg over 10 min
Days

HEART RATE CONTROL IN PATIENTS WITH HEART FAILURE AND WITHOUT ACCESSORY PATHWAY
Digoxin
I/B
0,25 mg IV each 2 h, up to 1,5 mg
60 min or
0,125-0,375 mg daily Digitalis toxicity,HB, HR
more
IV or orally
Amiodarone IIa/C
150 mg over 10 min
Days
0,5-1 mg/min IV
BP,HB,pulmonary toxicity,
skin discoloration, hypothyroidism,hyperthyroidism,corneal deposits,opticneuropathy, warfarin interaction,
sinus bradycardia.

NON-ACUTE SETTING AND CHRONIC MAINTENANCE THERAPY 4:

HEART RATE CONTROL
Metoprolol
I/C

Same as maintenance dose

4-6 h

Propanolol

I/C

Same as maintenance dose

60-90 min

Diltiazem

I/B

Same as maintenance dose

2-4 h

Verapamil

I/B

Same as maintenance dose

1-2 h

25-100 mg twice a day,

orally
80-240 mg daily in
divided doses, orally.
120-360 mg daily in
divided soses, slow
release available, orally
120-360 mg daily in
divided doses, slow
release available, orally

BP,HB,HR,asthma, HF
BP,HB,HR,asthma,HF
BP,HB,HF
BP,HB,HF,digoxin interaction.

HEART RATE CONTROL IN PATIENTS WITH HEART FAILURE AND WITHOUT ACCESSORY PATHWAY
Digoxin
I/C
0,5 mg by mouth daily
2 days
0,125 0,375 mg daily,
Digoxin toxicity,HB,HR
orally
Amiodarone
IIb/C
800 mg daily for 1 wk, orally
1-3 wk
200 mg daily, orally
BP,HB, Pulmonary
600 mg daily for 1 wk, orally
toxicity, skin discoloration,
400 mg daily for 4-6 wk,orally
hypothyroidism, corneal
deposits, optic neuropathy,
warfarin interaction, sinus
bradycardia.

Note:
Amiodarone can be used to control the heart rate in patients with AF when other measure are unsuccessful or
contraindicated.
Conversion to sinus rhythm and catheter ablation of the accessory pathway are generally recommended, pharmacologically therapy for rate control may be appropriate in certain patients.
If rhtyhm cannot be converted or ablated and rate control is needed, intravenous amiodarone is recommended.
4 Adequacy of heart rate control should be assessed during physical activity as well as at rest.
BP hypotension; HB heart Block;HR bradycardia; HF heart Failure.

TABLE 2 RECOMMENDED DOSES OF DRUGS PROVEN EFFECTIVE FOR PHARMACOLOGICAL CARDIOVERSION OF AF

DRUG

ADMINISTRATION

DOSAGE

Amiodarone

Oral

Inpatient: 1,2 1,8 g/day in divided dose until 10 g

total, then 200-400 mg/day maintenance or 30
mg/kg as single dose
Outpatient: 600-800 mg/day divided dose until 10g
total, then 200-400 mg/day maintenance

IV/oral

5-7 mg/kg over 30-60 min, then 1,2 -1,8 g/day

continous IV or in divided oral dose until 10 g total,
then 200-400 mg/day maintenance

Dofetilide

Oral

Flecainide

Oral
IV
IV

Creatinine clearance (ml/min)

! Dose
More than 60
! 600
40-60
! 250
20-40
! 125
Less than 20
! contra indicated
200-300 mg
1,5-3 mg/kg over 10-20 min
1 mg over 10 min; repeat 1 mg when necessary

Ibutilide
Propafenone

Oral
IV
Oral

Quinidine

600 mg
1,5-2 mg/kg over 10-20 min
0,75 -1,5 g in divided doses over 6-12 hour, usually
with a rate- slowing drug

POTENTIAL ADVERSE
EFFECTS
Hypotension, bradycardia, QT
prolongation, torade de
pointes(rare), GI upset,
constipation, phlebitis (iv)

QT prolongation, torsade de
pointes, adjust dose for renal
function, body size, and age.
Hypotension, atrial flutter with
high ventricular rate
QT prolongation, torsade de
pointes
Hypotension, atrial flutter with
highventricular rate.
QT prolongation, torsade de
pointes, GI upset, hypotension.

TABLE 3. ANTITHROMBOTIC THERAPY FOR PATIENTS WITH AF :

RISK CATEGORY
No Risk factors

RECOMMENDED THERAPY
Aspirin, 81 -325 mg daily

One moderate-risk factor

Aspirin,81-325 mg daily, or
Warfarin (INR 2,0-3,0, target 2,5)

Any high-risk factor or more than 1

moderate-risk factor

Warfarin (INR 2,0-3,0, target 2,5)

Less validated or Weaker Risk Factors

Moderate-Risk factors

High-Risk Factors

Female gender
Age 66 to 74 year

Age greater than o equal to 75 year

Hypertension
Heart failure
LV ejection fraction 35% or less
Diabetes mellitus

Previous stroke, TIA or embolism

Mitral stenosis
Prosthetic heart valve

Coronary artery disease

Thyrotoxicosis

PERTIMBANGAN MEMILIH OBAT ANTI-ARITMIA untuk ATRIAL FIBRILASI :

(Dari majalah Farmacia september 2007)

Tabel 1. Klasifikasi Obat Anti-aritmia Williams :

KELAS
I
IA
IB
IC
II
III
IV
Misc.

KERJA
Penghambat kanal natrium
Memperlama repolarisasi
Memperpendek repolarisasi
Efek terhadap repolarisasi
Penghambat bet-adrenergik
Memperlama repolarisasi
Menghambat kanal kalsium
Bermacam-macam

OBAT
Quinidine, Procainamide, Disopyramide
Lidocaine, Mexiletine. Tocainide, Phenytoin
Encainide, Flecainide, Propafenone, Moricizine
Propanolol,Esmolol, Acebutolol, l-Isotalol
Ibutilide, Dofetilide, Sotalol(d,l), Amiodarone, Bretylium
Verapamil, diltiazem, bepridil
Adenosin, digitalis, magnesium

TABEL 2 EFIKASI ANTI-ARITMIA :

KELAS
IA
IB
IC

EFIKASI
Fibrilasi atrium, aritmia ventrikuler
Aritmia ventrikuler
Av nodal reentry
WPW-related arrhythmias
Aritmia ventrikuler
Fibrilasi atrium, (aritmia ventrikuler)
Fibrilasi atrium
Aritmia venrikuler
Fibrilasi atrium
Atrial automaticities
AV nodal reentry
AV nodal reentry
Orthodromic tachycardia
AV nodal reentry
Fibrilasi atrium
Trosade de pointes

II
III
IV
ADENOSINE
DIGITALIS
MAGNESIUM

TABEL 3. PERTIMBANGAN UNTUK MEMULAI ANTI-ARITMIA :

Referensi

Risiko
proaritmia
1-8%

Faktor penting Penyakit

Jantung yang mendasari

Periode optimal
monitor

Anti-aritmia yang
digunakan

Kesimpulan

Pernah mengalami infark

miokard

24-48 jam

Procainamide, Quinidine,
Disopyramide,
Propafenone,Flecainide,
Soralol, Amiodarone

Myeburg
et al.
(1998)

1-8%

24-72 jam

Class IA dan III agents

Thibault
et al
(1999)

1-3%

Disfungsi ventrikel kiri

parah, perpanjangan QT,
rswpon prosritmia
sebelumnya, kecenderungan
bradikardiasimtomatik
Pria dengan riwayat gagal
ventrikuler, CHF

Observasi ketat dengan monitoring

electrocardiographic monitoring perlu
dilakukan, terutama untuk pasien yang
pernah mengalami infark miokard, pasien
tua, dan pasien yang menjalani konversi
elektrik.
Terapi antiaritmia sebaiknya dimulai di
rumah sakit

72 jam

Quinidine,
Propafenone,Flecainide,
Sotalol, Amiodarone

Chung et
al (1998)

2-8%

48-72 jam

Sotalol

Simons et
al (1997)

1,9%

CAD, penyakit jantung

valvuler, pernah menderita
artimia ventrikuler,
pemakaian pacemaker
permanen.
CAD, hipertensi,
kardiomiopati, perikarditis,
pernah menjalani operasi
jantung

72 jam

Quinidine, Disopyramide,
Propafenone, Flecainide,
Sotalol

Singh et
al. (2000)

1,2%

Pernah mengalami penyakit

jantung structural atau
interval QT/QTc panjang

72 jam

Dofetilide

Meisel et
al (1997)

Pada sebagian besar kasus, pemilihan dan

penggunaan antiaritmia secara hati hati akan
menghasilkan efek proaritmia yang cukup
rendah sehingga inisiasi antiaritmia tidak
harus di rumah sakit.
Pasien yang dilindungi dari bradikardia
dengan pacemaker sebaiknya di monitor di
rumah sakit selama inisiasi sotalol.
Hasil studi menunjukkan perawatan di rumah
sakit selama 72 jam untuk memulai terapi
antiaritmia dari takikardia supraventrikuler
lebih cost effective dibandingkan dengan
terapi obat dan bedah lainnya.
Pernah dilakukan inisiasi dan pwngaturan
dosis berdasarkan QTc dan ClCr ubtuk
meminimalisasi risiko tak
diinginkan(proaritmia)

TABEL 4. EFEK JANGKA PANJANG ANTI-ARITMIA terhadap MORTALITAS :

EFEK

TERAPI

Meningkatkan kematian

Encainide, Flecainide, Moricizine (uji klinis jangka pendek)

Mengurangi kematian

Penghambat beta-adrenergik (Propanolol, timolol, metoprolol), Sotalol.

Mungkin mengurangi
kematian

Amiodarone (uji klinis skala kecil)

Mungkin meningkatkan
kematian (data kurang

Disopyramide, Mexiteline, Procainamide, Quinidine, Tocainide

adekwat)
TABEL 5. EFEK SAMPING OBAT ANTI-ARITMIA :
OBAT (KELAS)

EFEK SAMPING dan TOKSISITAS

Gangguan gastrointestinal 30-50% pasien: diare, mual, muntah

Cinchonism

Hipotensi(terkait dengan penghambatan adrenergik-alfa)

Meningkatkan kadar serum digoksin, hingga bisa timbul toksisitas digitalis
Reaksi hipersensitif: ruam, emam, edema angioneurotik, heatitis
Trombositopenia yang reversibel

Hipotensi(terkait dengan penghambatan aktivitas ganglionik)

Gejala gangguan saluran cerna pada 10% pasien
Efek pada SSP: psikosis, depresi, halusinasi, pusing
Reaksi hipersensitif: demam, agranulositosis, Raynauds syndrome, mialgia, ruam
kulit, digital vaskulitis.

Penekanan SSP: pusing, disorientasi, bicara ngawur, tekanan pernafasan, nausea

Stimulasi SSP: kejang, psikosis, peregangan otot, tinnitus.
Penggunaan berbarengan dengan tocainide atau mexiletine bisa menyebabkan
toksisitas SSP tambahan, termasuk kejang.

Mexiletine (IB)

Efek pada saluran cerna: mual, muntah

Efek pada SSP: pusing, disorientasi, tremor.
Efek hematologik (0,2%) dengan tocainide: agranulositosis, penekanan sumsum
tulang , tromositopenia, yang bisa mengarah pada kematian.

Flecainide (IC)

Efek SSP pada 10-15% pasien : pusing, tremor, agitasi, sakit kepala, gangguan
penglihatan.

Meskipun obat-obat ini sangat efektif mengobati berbagai jenis aritmia, namun efek
sampingnya membatasi penggunaan klinis.
Toksisitas pulmonary dan fibrosis (10-15%, bisa menyebabkan kematian pada 10%
yang mengalami toksisitas).
Konstipasin pada 20% pasien.
Disfungsi hepatic; bisa irreversibel.
Efek SSP (ataksia, pusing, depresi, mimpi buruk, halusinasi)
Hipotiroid atau hipertiroid (5% dari pasien)
Cutaneous photosebsitivity (25% dari pasien)
Neuropati perifer
Peningkatan substansial dari LDL-kolesterol
Meningkatkan efek warfarin dan kadar serum digoksin, kinidin, prokainamid,
flecainide, teofilin, dan obat lain.
Waktu paruh 25-110 hari bisa memperlama toksisitas.

Anoreksia, mual, muntah, diare, nyeri abdomen, sakit kepala, pusing.

Efek samping bisa mengindikasikan toksisitas digitalis.

Waktu paruh yang singkat(kurang dari 10 menit) meminimalisir masalah efek

samping
Hipotensi, dan flushing pada 20% pasien
Dyspnea sementara, dada tidak nyaman pada lebih dari 10% pasien

KINIDIN ( IA)

Procainamide
(IA)

Lidocaine (IB)

Tocainide (IB)

Amiodarone (III)

Digitalis (Misc)

Adenosine (Misc)

Rasa logam
Sakit kepala, hipotensi, nausea.