Atrial Fibrillation (AF) overview

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Atrial fibrillation (AF): Supraventricular tachyarrhythmia characterized by disorganized atrial electrical activity and progressive deterioration of atrial electromechanical function.

Classified as:

  • Paroxysmal AF: Self-terminating episodes, usually <7 days
  • Persistent AF: Sustained arrhythmia for >7 days, do not self-terminate; requiring pharmacologic or DC cardioversion to restore sinus rhythm
  • Permanent AF: Arrhythmia which lasts for more than one year; cardioversion has failed or has led to a decision not to be attempted to restore sinus rhythm (or AF has been accepted by patient and physician and no further attempts made to restore sinus rhythm

Ref: Healey JS etal. Canadian Journal of Cardiology 2011; 27: 31-37




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  • Cardiac and Pulmonary disease
    • Hypertension
    • Coronary artey disease (CAD)/ myocardial infarction (MI)
    • Congenital/structural heart disease
    • Valvular heart diseases i.e. mitral regurgitation and aortic stenosis
    • Supraventricular tachyarrhythmia's including (Wolff-Parkinson-White syndrome, atrial flutter and tachycardia)
    • Previous heart surgery
    • Sick sinus syndrome
    • Cardiomyopathy/ myocarditis/ pericarditis
    • Chronic obstructive pulmonary disease (COPD)/ pneumonia
    • Pulmonary embolism or hypertension
  • Drug use
    • Alcohol/ cocaine/ caffeine
    • Methamphetamines
    • Digoxin toxicity
  • Endocrine disorders
    • Hyperthyroidism
    • Pheochromocytoma
  • Neurogenic
    • Subarachnoid hemorrhage
    • Large ischemic stroke
  • Familial atrial fibrillation
  • Lone (idiopathic) AF: Lone AF describes paroxysmal, persistent, or permanent atrial fibrillation in patients without underlying pathology
  • Other:
    • Obesity/ obstructive sleep apnea
    • Vagally medicated (habitual aerobic training)


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Prevalence and incidence increases with age.

Estimated Prevalence:

Approximately 1% of the general population has 1 in 4 life time risk of developing AF.

Distribution of prevalence according to the age is as follows:


  • <60 years of age          0.1%
  • 60-80 years of age       1-4%
  • >80 years of age          9%


Estimated Incidence:


  • ≤50 years of age          0.5%/1000/year
  • ≥70 years of age          9.7/1000/year


Gender predominance: Male > Female

Overall AF affects: Approximately 200,000 to 350,000 Canadians and 2.2 million Americans.

Ref: Heart and stroke foundation statistics


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Genesis of atrial fibrillation (AF):

  • Usually involves foci of cells in the left atrium in vicinity of the pulmonary vein
  • Increased adrenergic discharges stimulate these cells (rapid firing) which are followed by a vagal response
  • Subsequent generation of a multitude of atrial wavelets → nonhomogeneous conduction in the left atrium → intraatrial reentry phenomenon and continuation of atrial fibrillation (AF)

Mechanism of thromboembolism:

  • Stasis → clot formation → embolization


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Clinical Presentation:


  • Often asymptomatic; diagnosed incidentally on a routine examination
  • Palpitations/ fatigue/ anxiety
  • Shortness of breath/ chest pain
  • Hypotension/ lightheadedness/ confusion

Symptoms secondary to cardioembolism:

  • Stroke or transient ischemic attack (TIA)
  • Ischemic limb (cold pulseless limb)
  • Ischemic bowel (abdominal pain, discomfort)

Note: Risk of cardioembolism is the same whether permanent or paroxysmal atrial fibrillation (PAF).

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Differential Diagnosis:
  • Atrial flutter (AFL)
  • Atrial tachycardia
  • Atrioventricular nodal reentry tachycardia (AVNRT)
  • Paroxysmal supraventricular tachycardia (PSVT)
  • Wolff-Parkinson-White syndrome (WPW)


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Investigation and Workup:


  • Identify reversible causes (e.g. hyperthyroidism, ventricular pacing, exercise, etc.)
  • Identify risk factors (e.g. hypertension, sleep apnea)
  • History of potential triggers (e.g. alcohol, intensive aerobic training)
  • Family history of atrial fibrillation (particularly lone AF)
  • Medication history for atrial fibrillation, both for efficacy and adverse effects
  • History of lightheadedness/ presyncope


Full cardiac and pulmonary exam is valuable in reaching a definitive diagnosis and include the following:

  • Blood pressure, pulse and respiratory rate, including height and weight
  • Obesity predisposes to sleep apnea; both are associated risk factors, which should be treated with life style changes
  • Jugular venous pressure, carotid and peripheral pulses should be checked


  • Complete blood count
  • Coagulation (PTT, INR)
  • Serum electrolytes
  • Renal function tests
  • Liver function tests
  • Thyroid function tests
  • Fasting lipid profile
  • Fasting glucose
  • Toxicology screen
  • 12 lead electrocardiogram (ECG)

Imaging studies may include:

  • Transthoracic echocardiogram/Transesophageal echocardiogram (TTE/TEE)
  • Chest radiography
    • To rule out cardiopulmonary diseases and cardiomyopathies
  • Ambulatory blood pressure monitoring
    • In case of borderline hypertension
  • Electrophysiology study
    • In patients with documented regular supraventricular tachycardia for catheter ablation
  • Sleep study
    • For patients with symptoms of obstructive sleep apnea
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  • Treatment of atrial fibrillation (AF) focuses on ventricular rate and rhythm control, along with prevention of thromboembolism
  • Primary goal:
    • Amelioration of symptoms
    • Prevent recurrent arrhythmias
    • Prevent stroke and cardiomyopathy

Acute Setting Management

1. Hemodynamically unstable:

  • Electric cardioversion (defibrillation)
    • Start with 150-200 joules biphasic waveform in synchrony with the R wave
  • IV Heparin
    • 60 units/kg loading dose followed by 12 units/kg per hour to maintain an aPTT of approximately 1.5-2 times the control value
  • Low molecular weight heparin (LMWH) may also be used
  • Atropine (1 mg IV) should be readily available to treat prolonged pauses


Note: Anticoagulation may or may not be used in this setting. Patients with known AF/AFL <48 hr may undergo cardioversion without prior or subsequent anticoagulation. However, prior anticoagulation is advised for AF/AFL of unknown duration (or ≥48hr) or if patient is at high risk of stroke (mechanical or valvular heart disease, previous TIA or stroke). Such patients require ≥4 weeks of oral anticoagulation post cardioversion.


Ref: Ian G. Stiell et al. Canadian Journal of Cardiology 2011; 27: 38-46


2. Hemodynamically stable (AF or atrial flutter

duration <48 hours)


In selected patients, initial therapy with rate slowing agent is acceptable while waiting for spontaneous cardioversion, such as

  • Beta blockers
  • Calcium channel blockers (CCBs)
  • Digoxin (second line therapy)


Ref: Ian G. Stiell et al. Canadian Journal of Cardiology 2011; 27: 38-46.

Caveat: In special circumstances like Wolff-Parkinson-White syndrome (presence of an extra, abnormal electrical pathway in the heart leading to tachycardia), avoid beta blockers, CCBs, digoxin, and adenosine; consider intravenous anti-arrhythmic e.g.


  • Procainamide: 15-17 mg/kg IV over 60 min slow infusion
  • Ibutilide: 1-2 mg IV over 10-20 min; pretreat with MgSO4 1-2 mg IV


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If patient is still in AF, cardioversion without prior anticoagulation may be considered in low risk patients <48h


a) Pharmacological cardioversion:

Class Ia:

  • Procainamide: 15-17 mg/kg IV over 60 min


Class Ic:

  • Propafenone (oral): 450 mg (wt. <70 kg); 600 mg (wt. ≥70 kg)
  • Flecainide (oral): 200 mg (wt. <70 kg); 300 mg (wt. ≥70 kg)


Class III:

  • Ibutilide: 1-2 mg IV over 10-20 min; pretreat with MgSO4 1-2 mg IV


Note: Class Ic drugs (propafenone, flecainide ) should be used in combination with AV nodal blocking agents (beta-blockers or calcium-channel blockers) to avoid paradoxical increase in ventricular rate due to drug induced conversion of atrial fibrillation (AF) to atrial flutter (AFL). Class Ic should also be avoided in patients with structural heart disease.


b) Electrical cardioversion:

Recommended in case of pharmacological cardioversion failure.


  • Prophylactic anti-arrhythmic drugs before electrical cardioversion in emergency department is recommended in order to decrease early recurrence of AF or AFL and to enhance cardioversion efficacy

Ref: Ian G. Stiell et al. Canadian Journal of Cardiology 2011; 27: 38-46


c) Oral anticoagulant (OAC):


  • For high risk patients (e.g. valvular heart disease, recent stroke/TIA) OAC use for 3 weeks prior to cardioversion is recommended. In addition OAC is recommended for ≥4 weeks of post cardioversion. Antithrombotic therapy with OAC or Acetylsalicylic acid (ASA) is then based on risk of recurrent AF and CHADS2 score

CHADS<sub>2</sub> score

3. Hemodynamically stable (AF or AFL duration ≥48



  • Start with rate slowing agents (beta blockers, CCBs, and digoxin)
  • If there is no optimal response with rate slowing therapy, then consider cardioversion
  • Perform ECHO (TEE or TTE) to exclude thrombus before cardioversion
  • If no thrombus, then start cardioversion (preferably electric cardioversion) with IV heparin
  • Followed by oral anticoagulant (OAC) therapy thereafter for at least 4 weeks
  • If thrombus is present or ECHO is not available then give OAC (warfarin [INR 2-3] or dabigatran or rivaroxaban or apixaban) for 3 weeks before and at least 4 weeks post cardioversion
  • Prophylactic treatment with antiarrhythmic drugs is advisable after cardioversion in high risk patients, in view of high relapse

Ref: Ian G. Stiell et al. Canadian Journal of Cardiology 2011; 27: 38-46.


Special considerations:

Cardioversion in patients with implanted pacemakers and defibrillators


  • The electrode paddle should be at least 8 cm away from the pacemaker battery
  • Anteroposterior paddle positioning is recommended
  • Biphasic shocks are preferred
  • After cardioversion, the device should be evaluated to ensure normal function


AV junction ablation and implantation of a permanent pacemaker


  • Indicated in symptomatic patients with uncontrolled ventricular rates during atrial fibrillation despite maximally tolerated combination pharmacologic therapy

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Maintenance Therapy

  • Rate control
  • Rhythm control
  • Thromboembolic prophylaxis


1) Rate Control

Beta blockers, calcium channel blockers (CCBs):

  • Usually first line rate control agents in most patients without past history of myocardial infaction (MI) or left ventricular dysfunction (LVD)



  • IV: 0.5-1 mg; usual dose 0.1-0.4 mg IV once daily
  • Oral: 0.75-1.5 mg PO; usual dose 0.125-0.5 mg once daily
  • Not to be used for initial therapy in active patients; usually used as initial therapy in patients who are sedentary or who have left ventricular systolic dysfunction.
  • May be used as adjunct with beta blockers or CCBs in whom rate control is not achieved.



  • 400 mg PO TID over 5-7 days, then 400 mg/day over 1 month, then 200 mg/day
  • Usually reserved when other means are not feasible or are insufficient for rate control (because of adverse effects).



  • 400 mg PO BID with meals
  • Indicated for treatment of patients with non-permanent AF
  • Reduces hospitalizations due to AF
  • May be used as adjunct with beta-blockers, calcium channel blockers and used with caution with digoxin, if ventricular rate is uncontrolled despite therapy
  • Requires regular monitoring of liver function


HOWEVER, this agent is now contraindicated in:

  • Permanent AF, duration at least 6 month
  • Severe heart failure (NYHA stage IV) or unstable hemodynamic conditions
  • Left ventricular ejection fraction (LVEF) <40%
  • 2nd or 3rd degree AV block or sick sinus syndrome (SSS); unless functioning pacemaker present


Catheter ablation:

  • Atrioventricular (AV) junction ablation and permanent pacemaker implantation may be employed in those refractory to maximum combined medical therapy
  • OAC therapy be continued following AF ablation in patients with
    • i) CHADS2 score ≥1
    • ii) Mechanical heart valve


2) Rhythm Control

Anti-arrhythmic agents in maintenance therapy:

Generally reserved for patients with AF or AFL who remain symptomatic with rate control therapy or in whom rate control therapy is unlikely to control symptoms, agents used include:


Propafenone or Flecainide - Class I:

  • Used with structurally normal heart
  • Fast onset of action


Sotalol - Class III:

  • Avoid in decompensated congestive heart failure
  • Not very effective in converting recent onset AF to sinus rhythm


Dofetilide - Class III:

  • Not available in Canada


Amiodarone - Class I, II, III, and IV:

  • Effective but has extensive toxicity
  • Used in those with severely depressed LV function
  • Usually indicated in patients with recent-onset AF and structural heart disease


Dronedarone - Class III:

  • Initially considered less toxic, but also less effective than amiodarone and is used to lower side effects with acceptance of higher recurrence of AF
  • Contraindications: Permanent AF/severe heart failure/LVEF <40% / 2nd or 3rd degree AV block (as discussed in rate control above)


"Pill in the Pocket" for selected patients with atrial fibrillation


  • Self-treatment with intermittent antiarrhythmic drug therapy (propafenone or flecainide) is usually recommended; as an alternative to daily antiarrhythmic therapy, in symptomatic patients with infrequent long lasting episodes of AF

Caveat: Avoid oral antiarrthymic therapy in patients with AF/AFL or advanced sinus or AV nodal disease unless pacemaker or defibrillator has been installed.

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3) Thromboembolic Prophylaxis

(prevention of thromboembolic complications and bleeding risk)

a) Patients with AF often require prophylaxis with

anticoagulant therapy, unless contraindicated


Therapeutic choices include:


  • IV heparin/low-molecular-weight heparin (LMWH) (may be considered for short term prophylaxis)
  • Dabigatran
  • Rivaroxaban
  • Apixiban
  • Warfarin
  • Acetylsalicylic acid (ASA)


The therapy in turn is based on clinically relevant thromboembolic risk factors which are summarized as follows:


Major risk factors are considered:

  • Previous stroke, transient ischemic attack (TIA)
  • Previous systemic embolism
  • Age >65 years


Clinically relevant non-major risks:

  • Heart failure or severe to moderate LV systolic dysfunction (e.g. LVEF <40%)
  • Hypertension
  • Diabetes mellitus
  • Female sex
  • Age 65-74 years
  • Vascular disease


b) The risk/benefit ratio for patient selection has

been outlined in number of scales/tools, which

have been summarized in one table for convenience


c) Based upon the therapeutic bleeding risk

stratification scores (HAS-BLED score) in AF:


  • Patients with HAS-BLED Score ≥3 indicates increased one year bleeding risk on anticoagulation, sufficient enough to justify caution or more regular review.


d) Special considerations in patient who are on

prevention of thromboembolic complication:


Subclinical Atrial Fibrillation (SCAF):


  • Appears to have a lower risk of stroke as compared to those with clinical AF
  • Uncertainty remains regarding the duration AF above which stroke risk is increased
  • OAC therapy may be considered for patients >65 years or CHADS2 score >1 with episodes of SCAF lasting > 24 hours, or for shorter episodes in high-risk patients (such as those with a recent cryptogenic stroke)


Patients on antiplatelet therapy or OAC scheduled for surgery:


Discontinuation of antithrombotic therapy


For CHADS2 ≥3 or high risk of stroke (e.g. prosthetic valve, recent stroke, TIA, rheumatic valve disease)

  • Decision to discontinue antithrombotic agent depends on advantages and disadvantages of the patient's condition at that time with other risk factors
  • For those on OAC, discontinuation followed by bridging therapy with LMWH or IV heparin pre-procedure might be an option

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1) Electric cardioversion:

  • Safe and effective method for quick restoration of sinus rhythm:
    • If AF <48 hrs proceed with cardioversion
    • If AF ≥48 hrs or of unknown duration anticoagulant therapy is suggested (see "Hemodynamically Stable AF or AFL duration 48 hr" section above)
    • Biphasic external defibrillators are preferred
    • Start with lower possible dose in small size patient
  • Electrode placement positions:
    • Anteroposterior electrode placement (more effective)
    • Anterolateral placement
  • If initial shocks are unsuccessful:
    • Reposition electrodes and repeat cardioversion
  • Outpatient/ambulatory cardioversion can be undertaken:
    • In hemodynamically stable with no underlying severe heart disease
  • Post procedure monitoring:
    • Blood pressure, heart rate and telemetry for ≥3 hrs


2) Catheter ablation:

  • Is chosen as a first line therapy in highly selected patients with symptomatic paroxysmal AF
  • AF ablation should not be considered as an alternative to oral anticoagulation, and initiation of anticoagulation should not be delayed in patients with high thromboembolic risks


Potential sites for ablation:


a) Accessory pathway


  • Indicated in patients with evidence of ventricular pre-excitation during AF, such as rapid ventricular rates, syncope
  • Definitive therapy for patients with Wolff-Parkinson-White syndrome


b) AV node ablation and implantation of a

permanent pacemaker


  • For those with uncontrolled ventricular rates refractory to maximal pharmacologic therapy, a pacemaker and indefinite anticoagulant therapy is often required


c) Left atrial catheter ablation


  • Effective for either paroxysmal or chronic AF


d) Pulmonary vein isolation ablation (PVI ablation

or PVA)


  • Effective in patients who have "paroxysmal" AF

3) Surgical ablation:

Usually reserved for those patients who have failed a catheter ablation strategy or who have planned concomitant cardiac surgery.


Procedures usually used are:


  • Maze procedure
  • Cox Maze III procedure
  • Minimally invasive surgical ablation (e.g.)
    • Wolf Mini Maze
    • Saltman Microwave Mini Maze


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Beta-adrenergic blocking agents

  • ➢ Cardioselective
    • Atenolol
    • Esmolol
    • Metoprolol
  • ➢ Non-cardioselective
    • Propranolol
    • Sotalol



  • Block Beta receptors
  • Decrease heart rate and cardiac output
  • Decrease renin release


Dose: Cardioselective


Atrial fibrillation

  • 2.5-5 mg slow IV infusion over 2-5 minute; Max. 10 mg over 10-15 minute



SVT/Postoperative tachycardia/Hypertension (gradual control)

  • 500 mcg/kg IV over 1 minute; then 50 mcg/kg/minute infusion over 4 min; Max of 300 mcg/kg/min
  • Titration: Increased by 50 mcg/kg/minute (once in 4 mins) as needed
  • Note: If no response within 5 minute, may give 2nd loading dose of 500 mcg/kg over 1 minute, then 100 mcg/kg/minute infusion over 4 minute


Intraoperative tachycardia/Hypertension (immediate control)

  • 1.5 mg/kg IV bolus over 30 sec.; Then 0.15 mg/kg/minute infusion, if necessary; Max. 0.3 mg/kg/minute



Atrial fibrillation/Supraventricular tachycardia

  • Acute treatment: 2.5-5 mg IV every 2-5 minutes; Max. 15 mg over 10-15 minute
  • Maintenance (immediate release): 25-100 mg PO BID

Dose: Non-cardioselective



  • Intravenous: 1-3 mg slow IV push every 2-5 mg up to total of 5 mg
  • Regular Tablet: 10-30 mg PO QID or TID


Sotalol: (antiarrhythmic agent class III & II)

  • 40-160 mg PO twice daily; usual initial dose can be 80 mg PO twice daily, if required may go up to 240-320 mg PO per day

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Calcium channel blocking agents (CCBs)

  • Diltiazem
  • Verapamil



  • Blocks calcium influx by binding to the L-type calcium channels in the heart and in smooth muscle of the peripheral vasculature
  • Decreases intracellular calcium leading to a reduction in muscle contraction
  • Significant reduction in afterload, with no effect on preload


Dose: Non-Dihydropyridines



Supraventricular tachyarrhythmias

  • 0.25 mg/kg IV over 2 minute; if desired response not achieved in 15 minutes, may repeat 0.35 mg/kg IV bolus over 2 minute; then follow with continuous infusion at 10 mg/hr (range 5-15 mg/hr) for up to 24 hr, if required
  • Note: Infusions >24 hrs or >15 mg/hr are not recommended



Chronic atrial fibrillation/PSVT (prophylaxis)

  • Immediate-release: 240-480 mg/day PO divided in 3-4 doses; usual 120-360 mg/day in 3-4 divided doses


Supraventricular tachyarrhythmias

  • Dosage: 2.5-5 mg IV over 2 minute; may repeat 5-10 mg IV 15-30 minute after the initial dose if required; Max. 20-30 mg

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  • Class Ia
    • Procainamide
  • Class Ic
    • Propafenone
    • Flecainide
  • Class III
    • Ibutilide
    • Amiodarone
    • Ibutilide



  • Complete mechanism of antiarrhythmic action is not known
  • Depress Na conductance and block K+ channel → resultin in increased action potential duration (APD) and effective refractory period (ERP)
  • Ic agents block Na+ channels more potently than the Ia drugs and has some beta-blockade activity


Dose: Class Ia:



Atrial Fibrillation

  • Initial Loading dose: 15-17 mg/kg slow infusion over 60 minutes or 100 mg/dose repeated every 5 minutes (rate not to exceed 50 mg/minute) to a total dose of 1 g
  • Maintenance: 1-4 mg/minute IV continuous infusion


  • Oral: Initially 1.25 g PO; followed by 0.75 g PO after 1 hour interval. If there are no change on ECG, give additional doses of 0.5-1 g every 2 hours until arrhythmia is interrupted or until toxic effects appear
  • Maintenance (extended-release): Up to 50 mg/kg/day PO in equally divided doses every 6 hrs starting 2 to 3 hours after the last dose of conventional tablets


Hemodynamically stable monomorphic VT/Pre-excited atrial fibrillation (ACLS)

  • Loading dose as IV Infusion 20-50 mg/minute Or 100 mg every 5 minutes (rate not to exceed 50 mg/minute), until the arrhythmia is suppressed, a fall in BP of >15 mmHg occurs, excessive widening of the QRS complex (≥50%) from baseline or prolongation of the PR interval occurs, severe adverse effects appear, or a total dose of 17 mg/kg is given
  • Maintenance: Followed by continuous infusion of 1-4 mg/minute


Dose: Class Ic



Paroxysmal atrial fibrillation ("Pill-in-the-pocket")

  • Weight <70 kg: 450 mg PO
  • Weight ≥70 kg: 600 mg PO
  • Avoid repeating in ≤24 hrs


Recent onset atrial fibrillation

  • 150 mg PO given every 8 hours (total of 450 mg/day). May increase in 3-4 days interval to 300 mg PO every 12 hours (total of 600 mg/day) and if required may increase dose to 300 mg PO every 8 hours (900 mg/day)



Prevention of PSVT/Paroxysmal atrial fibrillation

  • 50 mg PO BID, may increase by 50 mg PO BID at 4 day intervals; Max. 300 mg/day


Paroxysmal atrial fibrillation - "pill-in-the-pocket" dose

  • Weight <70 kg: 200 mg PO daily; weight ≥70 kg: 300 mg PO daily

Note: Patient must be on an AV nodal-blocking agent prior to initiation of antiarrhythmic. No more than one dose during a 24-hour period.


Dose in renal impairment:

  • If CrCl <35 ml/minute, initiate 100 mg PO daily OR 50 mg PO BID: may increase dose at 4 day intervals cautiously, if needed


Dose: Class III



Atrial fibrillation/flutter

  • <60 kg: 0.01 mg/kg IV infusion over 10 minutes
  • ≥60 kg: 1 mg IV infusion over 10 minutes


Note: May repeat 2nd dose after 10 minutes


Atrial fibrillation/flutter after cardiac surgery

  • <60 kg: 0.005 mg/kg over 10 minute; ≥60 kg: 0.5 mg IV infusion over 10 minutes
  • Note: May repeat one additional time. If arrthymia terminates discontinue the infusion



Atrial fibrillation pharmacologic cardioversion

  • 5-7 mg/kg IV over 30-60 minutes; followed 1.2-1.8 g/day IV continuous infusion or PO in divided doses until total of 10 g
  • Maintenance: 200-400 mg/day in divided or single dose


  • Inpatient: 1.2-1.8 g PO daily in divided doses up to a total of 10 g
  • Maintenance: 200-400 mg/day PO in divided or single dose


  • Outpatient: 600-800 mg PO in single or divided dose; up to a total of 10 g
  • Maintenance: 200-400 mg/day in divided or single dose


Recurrent atrial fibrillation

  • 10 mg/kg/day PO in single or 2 divided doses for 14 days; then 300 mg PO daily for 4 weeks, followed by of 200 mg PO daily for maintenance OR
  • 400 mg PO TID for 5-7 days; then 400 mg /day for 1 month; followed by 200 mg/day



Atrial fibrillation/Flutter

  • 400 mg PO BID with meals


Cardiac Glycoside

  • Digoxin



Exact mechanism of action not known; however, the acceptable hypothesis is as follows:

  • Inhibition of the sodium/ potassium ATPase pump in myocardial cells results in a transient increase of intracellular sodium, which in turn promotes calcium influx via the sodium-calcium exchange pump leading to increased contractility
  • There is a direct effect on the conductivity of A-V node which is delayed; slowing the rate of origin of impulses from the S-A node. In short heart rate becomes slow. These effects are largely due to parasympathetic stimulation





AF + Heart failure

  • Acute management: Loading dose 250 mcg IV (0.25 mg) every 2 hours up to total of 1500 mcg (1.5 mg) in a day
  • Non-acute management: 500 mcg (0.5 mg) PO daily for 2 day
  • Maintenance: 125-375 mcg (0.125-0.375 mg) IV/PO daily


Supraventricular tachyarrhythmia

Total digitalizing dose (TDD)

  • 500-1000 mcg (0.5-1 mg) IV/IM; start with 50% of the TDD, then one quarter of the TDD in each of 2 subsequent doses at 6-8 hr intervals
  • 750-1500 mcg (0.75-1.5 mg) PO; start with 50% of the total digitalis dose (TDD), then one quarter of the TDD in each of 2 subsequent doses at 6-8 hr intervals
  • Note: Obtain ECG 6 hours after each dose to assess potential toxicity.


Daily maintenance dose

  • 125-500 mcg (0.125-0.5 mg) PO daily
  • 100-400 mcg (0.1-0.4 mg) PO daily

Note: Intramuscular injections are not preferred due to severe pain at the sight of injection.

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  • ➢ Heparin (unfractionated)
  • ➢ Low-molecular-weight heparin (LMWHs)
    • Enoxaparin
    • Dalteparin
  • ➢ Oral anticoagulants (OAC)
    • Warfarin
    • Dabigatran
    • Rivaroxaban
    • Apixaban



  • Inhibits thrombus formation and prevent extension of existing thrombi
  • No direct lytic effect on established thrombi
  • Prolongs aPTT, PT and INR





Typical use for IV heparin

Symptomatic AF with consideration of cardioversion or thrombus detection on ECHO


AF with concomitant TIA or minor/small ischemic stroke

  • Initial IV bolus of ~60-80 IU/kg or 5000 IU
  • Followed by an infusion of 12 IU/kg/hr; Max. 1000 IU/hr
  • Adjusted to maintain an APTT to 1.5-2 times normal (usually 50 to 70 seconds)


Caveat: For patients with moderate or large strokes, the above may be modified to a low initial exposure for avoidance of supra-therapeutic PTT and potential risk of bleeding:


  • Initial IV bolus of ~30-40 IU/kg or 2500 IU or no bolus
  • Followed by an infusion of 12 IU/kg/hr; Max. 1000 IU/hr
  • Adjusted to maintain an APTT to 1.4-1.8 times normal (suggested, but adjusted at discretion of treating physician)


Low-molecular-weight heparin (LMWH):

May sometimes be used for patients with AF/AFL

  • Enoxaparin: 1 mg/kg every 12 hrs
  • Dalteparin: 200 IU/kg/day SC every 12 hrs or once daily



Prevention/treatment of thrombosis/embolism



Dose (Canada labelling):

  • Age <80 year: 150 mg PO BID if creatinine clearance >30 ml/minute
  • Age >80 years: 110 PO BID if creatinine clearance >30 ml/minute
  • Contraindicated in creatinine clearance <30 ml/minute


Dose (USA labelling):

  • 150 mg PO BID if creatinine clearance >30ml/minute
  • 75mg PO BID if creatinine clearance 15-30 ml/minute


Conversion from dabigatran to parenteral anticoagulant

  • Wait 12 hrs. after the last dose of dabigatran before switching to a parenteral anticoagulan


Conversion from vitamin K antagonists (e.g. warfarin) to dabigatran

  • Dabigatran should only be started after vitamin K antagonists have been discontinued, and the patient's INR <2.0


Conversion from dabigatran to vitamin K antagonists (e.g. warfarin)

  • Stop dabigatran for 12 hrs then begin warfarin protocol/nomogram (see above)



  • GFR ≥50 ml/minute: 20 mg PO daily
  • GFR 30-49 ml/minute: 15 mg PO daily



  • GFR >25 ml/minute: 5 mg PO BID; alternatively 2.5 mg BID may considered in patients with at least 2 of the following features: Age ≥80 years, body weight ≤60 kg, or serum creatinine ≥133 micromole/L (1.5 mg/dL)


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Clinical Trials:
  • AFFIRM - A comparison of rate control and rhythm control in patients with atrial fibrillation
  • ATHENA - Effect of Dronedarone on Cardiovascular Events in Atrial Fibrillation
  • AF-CHF - Rhythm Control versus Rate Control for Atrial Fibrillation and Heart Failure
  • AVERROES - Apixaban in Patients with Atrial Fibrillation
  • ARISTOTLE - Apixaban versus Warfarin in Patients with Atrial Fibrillation
  • RACE- Lenient versus Strict Rate Control in Patients with Atrial Fibrillation
  • ACTIVE W - Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W)
  • CTAF - Amiodarone to Prevent Recurrence of Atrial Fibrillation
  • Re-LY - Randomized Evaluation of Long Term Anticoagulant Therapy (RE-LY) With Dabigatran Etexilate
  • ROCKET AF - Stroke Prevention in Atrial Fibrillation
  • EMBRACE - Atrial Fibrillation in Patients with Cryptogenic Stroke
  • ENGAGE AF-TIMI 48 - Edoxaban versus Warfarin in Patients with Atrial Fibrillation
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Pipeline Agents:
  • PALLAS - Dronedarone in High-Risk Permanent Atrial Fibrillation


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Physician Resources:

1. Tips for Patient Care

Risk factor management:

  • Assess and treat modifiable risk factors for atrial fibrillation (AF) such as (hypertension, diabetes mellitus, coronary artery disease, thyrotoxicosis, mitral stenosis, alcohol and drug use/abuse etc.)


  • Advise patient and family members to compliance with medication
  • Advise for periodical INR assessment for patients receiving warfarin
  • Maintain INR 2.0-3.0 for AF and >2.5-3.5 in most patients with mechanical valves with or without AF
  • Be aware of drug-drug and drug-food interactions, particularly with patients on warfarin
  • Patient and family members should be aware of bleeding complication of anticoagulant therapy
  • Make patients aware of sign and symptoms of stroke
  • Avoid use of flecainide and propafenone in patients with structural heart disease
  • Over-the-counter (OTC) medications, such as nasal sprays and cold remedies, contain substances that can aggravate AF
  • Abrupt withdrawal of beta blockers may exacerbate symptoms
  • Digoxin clearance is reduced in renal insufficiency and dose adjustment may be required to avoid toxicity
  • IV calcium may produce arrhythmias in digitalized patients

Social and Stress factors:

  • Include family or social support in lifestyle modification


2. Scales and Tables


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Core Resources:

  • Canadian Cardiovascular Society Atrial Fibrillation Guidelines 2010: Prevention of Stroke and Systemic Thromboembolism in Atrial Fibrillation and Flutter
  • Cairns JA, Connolly S, McMurtry S, Stephenson M, Talajic M. CCS Atrial Fibrillation Guidelines Committee. Canadian Cardiovascular Society Atrial Fibrillation Guidelines 2010: prevention of stroke and systemic thromboembolism in atrial fibrillation and flutter.Can J Cardiol. 2011;27:74-90
  • Compendium of Pharmaceuticals and Specialties (CPS). Canadian Pharmacist association. Toronto: Webcom Inc. 2012
  • Day RA, Paul P, Williams B, et al (eds). Brunner & Suddarth's Textbook of Canadian Medical-Surgical Nursing. 2nd ed. Philadelphia: Lippincott Williams and Wilkins; 2010
  • Furie KL, Glodstein LB, Albers GW et al. Oral Antithrombotic Agents for the Prevention f Stroke in Nonvalvular Atrial Fibrillation: A Science Advisory for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2012; 43: 1-12 (DOI: 10.1161/STR.0b013e318266722a)
  • Foster C, Mistry NF, Peddi PF, Sharma S, eds. The Washington Manual of Medical Therapeutics. 33rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010
  • Gillis AM, Verma A, Talajic M, Nattel S, Dorian P CCS Atrial Fibrillation Guidelines Committee. Canadian Cardiovascular Society Atrial Fibrillation Guidelines 2010: rate and rhythm management.Can J Cardiol. 2011;27:47-59
  • Gillis AM, Skanes AC, CCS Atrial Fibrillation Guidelines Committee. Canadian Cardiovascular Society Atrial Fibrillation Guidelines 2010: implementing GRADE and achieving consensus.Can J Cardiol. 2011;27:27-30
  • Gray J, ed. Therapeutic Choices. Canadian Pharmacists Association. 6th ed. Toronto: Webcom Inc. 2011
  • Healey JS, Parkash R, Pollak T, Tsang T, Dorian P CCS Atrial Fibrillation Guidelines Committee. Canadian Cardiovascular Society Atrial Fibrillation Guidelines 2010: etiology and initial investigations. Can J Cardiol. 2011;27:31-37
  • O'Rourke R, Walsh R, Fuster V, eds.Hurst's the Heart Manual of Cardiology, 12th Edition. New York: McGraw-Hill; 2008
  • Katzung BG, Masters SB, Trevor AJ, eds. Basic and Clinical Pharmacology. 11th ed. New York: McGraw-Hill; 2009
  • Longo D, Fauci A, Kasper D, et al (eds). Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2011
  • McPhee SJ, Papadakis MA, eds. Current Medical Diagnosis & Treatment. 49th ed. New York: McGraw-Hill; 2010
  • Mitchell LB CCS Atrial Fibrillation Guidelines Committee. Canadian Cardiovascular Society Atrial Fibrillation Guidelines 2010: prevention and treatment of atrial fibrillation following cardiac surgery. Can J Cardiol. 2011;27:91-97
  • Pagana KD, Pagana TJ eds. Mosby's Diagnostic and Laboratory Test Reference. 9th ed. St. Louis: Elsevier-Mosby; 2009
  • Skidmore-Roth L. ed. Mosby's drug guide for nurses. 9th ed. St. Louis: Elsevier-Mosby; 2011
  • Skidmore-Roth L, ed. Mosby's nursing drug reference. 24th ed. St. Louis: Elsevier-Mosby; 2011
  • Stiell IG, Macle L CCS Atrial Fibrillation Guidelines Committee. Canadian Cardiovascular Society Atrial Fibrillation Guidelines 2010: management of recent-onset atrial fibrillation and flutter in the emergency department. Can J Cardiol. 2011;27:38-46
  • Skanes AC, Healey JS, Cairns JA. Focused 2012 Update of the Canadian Cardiovascular Society Atrial Fibrillation Guidelines: Recommendations for Stroke Prevention and Rate/Rhythm Control. Can J Cardiol 2012; 28: 125-136


Journals/Clinical Trials:

  • e-Therapeutics
  • Lexicomp
  • RxList
  • Epocrates


Journals/Clinical Trials:

  • Connolly SJ, Camm A.J, Halperin JL, etal. Dronedarone in High-Risk Permanent Atrial Fibrillation (PALLAS). N Engl J Med 2011; 365:2268-76
  • Connolly SJ, Eikelboom J, Joyner C, etal. Apixaban in Patients with Atrial Fibrillation. N Engl J Med 2011; 364:806-17
  • Genest J, McPherson R, Frohlich J, et al. 2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult - 2009 recommendations. Can J Cardiol 2009; 25: 567-579
  • Gladstone DJ, Spring M, Dorian P et al. Atrial Fibrillation in Patients with Cryptogenic Stroke. N Engl J Med 2014;370:2467-77
  • Granger CB, AlexanderJH, McMurray JJV, etal. Apixaban versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2011; 365:981-92
  • Okin PM, Wachtell K, Kjeldsen SE, et al.Incidence of atrial fibrillation in relation to changing heart rate over time in hypertensive patients: the LIFE study. Circ Arrhythm Electrophysiol. 2008; 1:337-43
  • Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation. N Engl J Med. 2011; 365:883-91
  • Roy D, Talajic M, Dorian P, et al for the Canadian Trial of Atrial Fibrillation Investigators, Amiodarone to Prevent Recurrence of Atrial Fibrillation. N Engl J Med 2000; 342:913-920
  • The ACTIVE Writing Group on behalf of the ACTIVE Investigators. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W).The Lancet. 2006: 367: 1903-1912
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Milan Gupta, MD, FRCPC, Associate Clinical Professor of Medicine, McMaster University, Staff Cardiologist, William Osler Health System, Brampton, ON Canada
.......................................... PHARMACY REVIEWER:
Wendy Gordon, B.Sc.(Pharm), ACPR, Pharm.D, Clinical Pharmacy Specialist, Fraser Health Authority (Royal Columbian Hospital), New Westminster, BC Canada

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