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.