AF :pharmacologicalagents updates

ByM.Wafaie Aboleineen ,MD ,FACC

Atrial Arrhythmia-RelatedHospitalizations in the U.S.

Atrial Fibrillation – 21%Atrial Fibrillation – 21%

VentricularFibrillation - 2%VentricularFibrillation - 2%

Ventricular Tachycardia - 10%Ventricular Tachycardia - 10%Miscellaneous - 21%Miscellaneous - 21%

ConductionAbnormailites- 8%

ConductionAbnormailites- 8%

Sick SinusSyndrome - 9%Sick SinusSyndrome - 9%

Premature beats- 6%Premature beats- 6%

ParoxysmalSupraventricularTachycardia - 6%

ParoxysmalSupraventricularTachycardia - 6%

Atrial Flutter- 4%Atrial Flutter- 4%

Adapted from Bialy et al.Stroke rate 1-3% withoutanticoagulation

20 –

15 –

10 –

5 –

0 –

Years

CumulativeFrequencyof AF (%)

OSA

Gami, et al. JACC 2007;49:565-71

Cumulative frequency curves for incident atrial fibrillation (AF) for subjects < 65 years of age with and without obstructive sleep apnea (OSA)during an average 4.7 years of follow-up. p = 0.002

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Number at RiskOSANo OSA

8442,209

7091,902

5691,616

4781,317

3971,037

333848

273641

214502

173393

134296

110217

94195

70130

4694

2969

828

Incidence of AF Based on Presence or Absence of OSA

No OSA

D-Dimer Prediction of Risk

Patients with elevated D-dimer levels experiencedhigher thromboembolic andcombined CV. events.

Sadanaga T, et. AL; J Am Coll Cardiol. 2010 May 18;55(20):2225-3.

The management cascade forpatients with AF

ACEI = angiotensin-converting enzyme inhibitor; AF = atrial fibrillation; ARB = angiotensin receptor blocker;PUFA = polyunsaturated fatty acid; TE = thrombo-embolism.

VALHeFT

Primary prevention of AFwith “upstream” therapy

aClass of recommendation.bLevel of evidence.ACEI = angiotensin-converting enzyme inhibitor; AF = atrial fibrillation; ARB = angiotensin receptor blocker.

Secondary prevention of AFwith “upstream” therapy

aClass of recommendation.bLevel of evidence.ACEI = angiotensin-converting enzyme inhibitor; AF = atrial fibrillation; ARB = angiotensin receptor blocker.

Risk factor-based point-basedscoring system - CHA2DS2-VASc

*Prior myocardial infarction, peripheral artery disease, aortic plaque. Actual rates of stroke incontemporary cohorts may vary from these estimates.

Adjusted stroke rate accordingto CHA2DS2-VASc score

The HAS-BLED bleeding risk score

*Hypertension is defined as systolic blood pressure > 160 mmHg. INR = international normalized ratio.

Approach to thromboprophylaxis in AF

AF = atrial fibrillation; CHA2DS2-VASc = cardiac failure, hypertension, age ≥ 75 (doubled), diabetes, stroke (doubled)-vasculardisease, age 65–74 and sex category (female); INR = international normalized ratio; OAC = oral anticoagulation, such as a vitaminK antagonist (VKA) adjusted to an intensity range of INR 2.0–3.0 (target 2.5).

Cardioversion, TOE andanticoagulation

AF = atrial fibrillation; DCC = direct current cardioversion; LA = left atrium; LAA = left atrial appendage; OAC = oral anticoagulant;SR= sinus rhythm; TOE= transoesophageal echocardiography.AF = atrial fibrillation; DCC = direct current cardioversion; LA = left atrium; LAA = left atrial appendage; OAC = oral anticoagulant;SR= sinus rhythm; TOE= transoesophageal echocardiography.

Date of download:1/28/2013

Copyright © The American College of Cardiology.All rights reserved.

From: New Oral Anticoagulants in Atrial Fibrillation and Acute Coronary Syndromes: Title and subTitleBreakESC Working Group on Thrombosis—Task Force on Anticoagulants in Heart Disease Position Paper

J AmCollCardiol.2012;59(16):1413-1425. doi:10.1016/j.jacc.2012.02.008Figure Legend:

Date of download:1/28/2013

Copyright © The American College of Cardiology.All rights reserved.

From: New Oral Anticoagulants in Atrial Fibrillation and Acute Coronary Syndromes: Title and subTitleBreakESC Working Group on Thrombosis—Task Force on Anticoagulants in Heart Disease Position Paper

J Am Coll Cardiol. 2012;59(16):1413-1425. doi:10.1016/j.jacc.2012.02.008Comparable Primary Efficacy Endpoints of Stroke or Systemic Embolism.

Figure Legend:

Date of download:1/28/2013

Copyright © The American College of Cardiology.All rights reserved.

From: New Oral Anticoagulants in Atrial Fibrillation and Acute Coronary Syndromes: Title and subTitleBreakESC Working Group on Thrombosis—Task Force on Anticoagulants in Heart Disease Position Paper

J Am Coll Cardiol. 2012;59(16):1413-1425. doi:10.1016/j.jacc.2012.02.008Comparable Primary Safety Endpoints of Major Bleeding

Figure Legend:

Rate and rhythm control of AF

aClass of recommendation. bLevel of evidence. AF = atrial fibrillation; EHRA = European Heart Rhythm Association.

Vernakalant hydrochlorideis a new atrial-selective, early-

activating K+ (IKur) and frequency-dependent Na+ channel blocker, andmay be a novel alternative to currentlyused agents for acute conversion of AFto sinus rhythm, especially if it is ofrelatively short duration

Camm AJ, JACC,2011

AVRO

• Primary endpoint (acute conversion to sinusrhythm [SR] within 90 minutes) for vernakalantvs. amiodarone: 51.7% vs. 5.2%, p < 0.0001

• Vernakalant median time to conversion, 11minutes

• Treatment-related adverse events: 27.6% vs. 8.6%at 2 hours; most common dysgeusia. Atrialflutter ↑ with vernakalant vs. amiodarone: 8.6%vs. 0.9%

Trial design: Patients with symptomatic recent onset atrial fibrillation (AF) wererandomized to receive either intravenous vernakalant or amiodarone. Patients werefollowed for 7 days.

Results

Conclusions

Camm AJ, et al. J Am Coll Cardiol 2011;57:313-21

(p < 0.0001)

Vernakalant(n = 116)

Primary endpoint

0

50

100

%51.7

5.2

(p < 0.0001)

37.0

9.5

50

Ready for dischargeat 2 hours

Amiodarone(n = 116)

0

100

%

• Vernakalant was superior to amiodaronefor acute conversion of AF to SR, althoughincidence of short-term adverse events washigher with vernakalant

• Proarrhythmic events were rare withvernakalant, except for atrial flutter

Pharmacological conversion of (recent-onset) AF

ACS = acute coronary syndrome; AF = atrial fibrillation; DCC = direct current cardioversion; i.v. = intravenous;N/A = not applicable; NYHA, New York Heart Association; p.o. = per os; QRS = QRS duration; QT = QT interval;T-U = abnormal repolarization (T-U) waves.

AF Efficacy: Maintaining NSR > 6 Months

0

10

20

30

40

50

60

70

NSR

, %

Nodrug

Quin Diso Prop Flec Sot Dof Azim Amio

ORGAN TOXICITY

• Negligible:– Dofetilide, flecainide, propafenone, sotalol,

dronedarone

• Acceptable:– Azimilide, disopyramide

• High:– Amiodarone, procainamide, quinidine

Choice of antiarrhythmic for the patientwith no or minimal structural heart disease

Choice of an antiarrhythmic drugfor AF control

aClass of recommendation.bLevel of evidence.AF = atrial fibrillation; AV = atrioventricular; LoE = level of evidence; NYHA = New York Heart Association.

Optimal level of heart rate control

Rate control of atrial fibrillationThe choice of drugs depends on life style and underlying disease

Drugs for rate control

ER = extended release formulations; N/A = not applicable. ‡Only in patients with non-permanent atrial fibrillation.

Acute rate control in AF

aClass of recommendation. bLevel of evidence.AF = atrial fibrillation; i.v. = intravenous.

Long-term rate control in AF

aClass of recommendation. bLevel of evidence.AF = atrial fibrillation; bmp = beats per minute; LV = left ventricular; NYHA = New York Heart Association.

Long-term rate control in AF

aClass of recommendation. bLevel of evidence.AF = atrial fibrillation; bmp = beats per minute; LV = left ventricular; NYHA = New York Heart Association.

Rate control during AF with heart failure

aClass of recommendation.bLevel of evidence.AF = atrial fibrillation; AP = accessory pathway; LVEF = left ventricular ejection fraction.

Rate control during AF with CHF

aClass of recommendation.bLevel of evidence.AF = atrial fibrillation; AV = atrioventricular; CRT = cardiac resynchronization therapy;LVEF = left ventricular ejection fraction; NYHA = New York Heart Association.

Choice between ablation and antiarrhythmic drug therapyfor patients with and without structural heart disease

†More extensive LA ablation may be needed; *usually PVI is appropriate.AF = atrial fibrillation; CAD = coronary artery disease; CHF = congestive heart failure; HT = hypertension; LVH = left ventricular hypertrophy;NYHA = New York Heart Association; PVI = pulmonary vein isolation. Antiarrhythmic agents are listed in alphabetical order within each treatment box.

Suggested doses and main caveats forcommonly used antiarrhythmic drugs

AF = atrial fibrillation; AV = atrioventricular; bpm = beats per minute; CYP = cytochrome P; ECG = electrocardiogram;LV = left ventricular; NYHA = New York Heart Association.

Suggested doses and main caveats forcommonly used antiarrhythmic drugs (Contd)

AF = atrial fibrillation; AV = atrioventricular; bpm = beats per minute; CYP = cytochrome P; ECG = electrocardiogram;LV = left ventricular; NYHA = New York Heart Association.

Suggested doses and main caveats forcommonly used antiarrhythmic drugs (Contd)

AF = atrial fibrillation; AV = atrioventricular; bpm = beats per minute; CYP = cytochrome P; ECG = electrocardiogram;LV = left ventricular; NYHA = New York Heart Association.