Chidiebere Eze, PharmD; Aug 20, 2017

Atrial Fibrillation
A supraventricular tachycardia characterized by uncoordinated atrial activation with consequent
deterioration of atrial mechanical function. May occur in isolation or in association with other arrhythmias
(e.g. atrial flutter or atrial tachycardia).

Incidence and Prevalence:

 1/3 of hospital admissions for cardiac
rhythm disturbances (most common)
 Increases in prevalence with age and
heart disease.
 Increased incidence of 66% in the past 20
years for AFib hospital admissions

Pathophysiology:
 Enhanced automaticity
 Reentry

Diagnosis:
 ECG: Irregularly irregular rhythm, erratic
waves between heartbeats. No P waves.

Clinical presentations:
 Palpitations, chest pain, dyspnea, fatigue, light-headedness, syncope, stroke, HF

Classification:
Management requires knowledge of presentation (paroxysmal, persistent or permanent).
 Valvular AFib: caused by structural changes in the mitral valve or congenital heart disease.
 Non-valvular AFib: Not caused by valvular disease.
 First episode
 Recurrent (≥2 episodes)
o Paroxysmal – terminates spontaneously ≤7 days (~24 hrs)
o Persistent – continues >7 days
o Permanent /Chronic – Ongoing long-term episode, failed cardioversion
 Secondary – AFib caused by underlying condition, e.g. MI, cardiac surgery, pulmonary disease,
hyperthyroidism, etc.

Treatment options: (Rate control preferred to rhythm control)

 Rate control: control ventricular rate. Allows adequate time for ventricular filling, avoids rate-
related ischemia, may improve hemodynamics. Goal of ~60-80 bpm at rest and 90 – 115 with
exercise.
 Rhythm control: restore/maintain sinus rhythm. ALSO requires attention to rate control.
 Anticoagulation: Regardless of either above, prevent thromboembolism by using antithrombotic
therapy before and after cardioversion.
 Chidiebere Eze, PharmD; Aug 20, 2017
Treatment Plan:

Monitor Follow-up

Healthy
lifestyle
Treat rate Medication

Calculate
How can I Aspirin (low Treat rhythm OR
CHADS2 VASc
prevent stroke? risk pts only) rate?
score Medication

FDA approved
anticoagulants Catheter
ablation
Treat rhythm

Cardioversion
Rate Control:
If rapid ventricular response, before antiarrhythmic
medication, give to prevent AV conduction. Surgery
 Medications:
o Class II: Beta-blockers (1st line)
 Slows HR
 Cardio selective: metoprolol, esmolol (Brevibloc)
 Co-morbid conditions: can use non-selective in HTN
o Class IV: Ca channel blockers
 Slows HR in AFib pts and reduces the strength of the muscle cell’s contraction
 nonDHP - diltiazem, verapamil
 Co-morbid conditions: can use in asthma/COPD, avoid in CHF
 Use when: MI without LV dysfunction, COPD, pregnancy, can’t tolerate BB
o Digoxin:
 Slows the ventricular rate mostly via enhancing vagal tone
 Use in conjunction with beta blockers or calcium channel blockers
 Co-morbid conditions: Can be an add-on in CHF
 Watch for toxicity (HF  0.5 – 0.8; Afib  0.8 – 1.5)

IV drug therapy Loading dose Maintenance dose

Esmolol 500 mCg/kg  1 min 50 – 300 mCg/kg/min
Metoprolol 2.5 – 5 mg  2mins X up to 3 doses
Propranolol 1 mg  1 min X up to 3 doses (2 min interval)
Diltiazem 0.25 mg/kg  2mins 5 – 15 mg/hr
Verapamil 0.075 – 0.15 mg/kg  2 mins 10 mg  30 min
If unresolved then…
0.005mg/kg/min
Digoxin 0.25 mg Repeat until max of 1.5 mg
Amiodarone 300mg  1 hr
10 – 50 mg/hr  24 hrs

Rhythm Control
For some who still have symptoms despite adequate rate control, restoration of NSR may be desired.
 Use TEE or Initiate anticoagulation ~3wks prior to & ~4wks post cardioversion to confirm absence
of atrial thrombi.
 Medications:
o Class I: Na+ channel blockers
 Contraindicated in heart failure
 Third line therapy
 Chidiebere Eze, PharmD; Aug 20, 2017
 Types:
 Ia – disopyramide, quinidine, procainamide
o Widens QT interval
 Ic – flecainide, propafenone
o Class III: K+ channel blockers
 Amiodarone: Long half-life, AV nodal blocking properties, used for
cardioversion AND maintaining NSR, hepatically metabolized, minimal
incidence of ventricular arrhythmias, extensive drug interactions and AE (liver,
thyroid, pulmonary, ophthalmic)
 Dronaderone: noniodinated derivative of amiodarone, decrease
hospitalizations from AFib, C/I with Class IV HF or recent decompensation,
caution in low EF, Major AE  Bradycardia, QT prolongation
 Ibutilide: Used only for conversion to NSR, eletrolyte replacement
 Dofetilide: Dosed based on renal function. Prefered in HF pts.
 Sotalol: Has both K+ and beta-blockade. C/I in HF. Excreted unchanged in urine.
Medications Cardioversion dose Oral MDD for Adverse effects Pearls
NSR
Amiodarone Oral/IV PO: LD: Bradycardia, hypotension, QT Preferred in pts with HF
(Cordarone) Inpt: 1.2-1.8g/day 600mg/day prolongation, torsades de pointes
Outpt: 600- x1month OR (rare), GI upset, constipation,
Class III 800mg/div. day until 1000mg/day phlebitis (IV)
10g, then MD of 200- x1week
400mg/day or Photosensitivity, pulmonary
30mg/kg as single MD: toxicity, polyneuropathy, hepatic
dose (inpt) 100-400mg toxicity, thyroid dysfunction, eye
complications
IV:
5-7mg/kg over 30-
60min, then inpt
dose as continuous IV
Dofetilide* Oral CrCl >60: 500mcg BID 500-1000mcg QT prolongation, Torsades de Preferred in pts with HF;
(Tikosyn) 40-60: 250mcg BID pointes; adjust dose for renal In-hospital EKG required
20-40: 125mcg BID function, body size and age for at least three days
Class III <20: Contraindicated
Flecainide Oral/IV PO: 200-300mg 200-300mg Hypotension, atrial flutter with Preferred in pts with little
(Tambocor) IV: 1.5-3mg/kg over (weight high ventricular rate, VT, HF, to no heart disease and
10-20min based) proarrythmias, torsades de preserved left ventricular
Class Ic Trough: 0.2-1 pointes systolic function;
mcg/mL Not recommended in pts
with chronic AFib
Ibutilide IV 1mg over 10 min; x QT prolongation, Torsades de Caution needed in pts
(Corvert) may repeat x 1 pointes, polymorphic ventricular with QT prolongation,
tachycardia, hypotension, hypokalemia, bradycardia
Class III headache hypomagnesemia
Propafenone Oral/IV PO: 600mg 450-900mg Hypotension, atrial flutter with Preferred in pts with little
(Rythmol) IV: IV: 1.5-2mg/kg (weight high ventricular rate, VT, HF, to no heart disease and
over 10-20min based) granulocytosis, angina, chest pain, preserved left ventricular
Class Ic atrioventricular block, systolic function
bradyarrhythmias, palpitations, C/I in structural heart
sinus arrest, drug-induced lupus, disease
bronchospasm
Quinidine Oral 0.75 to 1.5 g in 600-1500mg QT prolongation, Torsades de Dose adjust in CrCl <10
divided doses over 6- pointes, GI upset, hypotension
Class Ia 12h, usually with a proarrhythmias, hepatoxicity,
rate-lowering drug kidney disease, myelosuppression,
drug-induced lupus, Anti-SLUD
 Chidiebere Eze, PharmD; Aug 20, 2017
Disopyramide Oral Don’t start outside 400-750mg Torsades de pointes, HF, AntiSLUD Dose adjust in CrCl <50
(Norpace) hospital for - glaucoma, urinary retention, dry Can worsen HF
Class Ia cardioversion mouth Take on empty stomach
Procainamide Oral Don’t start outside 1000-4000mg Torsades de pointes, Lupus-like Dose adjust in CrCl <50
hospital for syndrome, GI symptoms, Hepatic (Child-Pugh score
Class Ia cardioversion agranulocytosis, aplastic anemia, <8)
coagulation disorder, arrhythmia,
hepatotoxicity, Anti-SLUD
Sotalol* Oral x 160-320mg Torsades de pointes, HF, Continuous EKG required
(Betapace) bradycardia, exacerbation for three days after
of chronic obstructive or initiation of therapy;
Class III bronchospastic lung disease, Avoid in HF, AV block,
proarrhythmias, heart block, HR<50, asthma, CrCl<40
asthma
* Adjust for renal function and QT interval response

Non-pharmacologic therapies

 Cardioversion: Low-energy, sedation usually needed. Can be used in emergency if

hemodynamically unstable
 AV nodal ablation: ablate the AV node and chronically pace the ventricles; Often used when rate
control ineffective
 Pulmonary Vein ablation  ablates the origin of the abnormal atrial foci. Key component of Wolf
Mini Maze

Non-pharmacological control
 Restore normal sinus rhythm:
o Cardioversion
 Rate/rhythm control:
o Radiofrequency ablation “catheter ablation”
 Chidiebere Eze, PharmD; Aug 20, 2017
 Permanent rate control:
o AV node ablation  need ICD
 Permanent rhythm control:
o Maze procedure  surgical ablation
o Pulmonary vein ablation

Anticoagulation:
 Warfarin, aspirin, and clopidogrel (Plavix): most commonly used oral agents for anticoagulation.
 Warfarin reduces risk of stroke by ~68%, ASA reduces risk of stroke by ~21%.
 Contraindications to warfarin therapy include hypersensitivity to warfarin, severe liver disease,
recent trauma or surgery, and active bleeding

CHADS2 VASc Scoring system:

Condition Score
C CHF 1
H HTN 1
A2 Age ≥ 75 2
D Diabetes 1
S2 Prior stoke, TIA, thromboembolism 2
V Vascular disease (e.g. PAD, MI, aortic plaque) 1
A Age 65–74 years 1
Sc Sex category (i.e. female sex) 1

Score Risk Recommended therapy

Male (0) Female (1) Low No anticoagulation
Male (1) - Moderate No anticoagulation or oral anticoagulation or ASA may be considered
Male and Female (≥ 2) High Oral anticoagulation is recommended.
Warfarin, dabigratran, rivaroxaban, apixaban
*If unable to take oral anticoagulants, use ASA + Plavix

Medications Dose Adverse effects Reversal agent Pearls

Dabigatran* Oral CrCl>30: 150mg BID Indigestion, upset Idarucizumab *Not for pts with artificial heart valves*
(Pradaxa) CrCl 15-30: 75mg BID stomach/ burning (Praxbind), 4- Swallow whole, do not crush, chew or
CrCl <15: Avoid and/or pain factor PCC empty pellets
After opening, use within 4 months
Take with full glass of Keep in original package
water, with/without Superior to warfarin, same bleeding risk
food
Rivaroxaban* Oral CrCl >50: 20mg QD Take with evening 4-factor PCC *Not for pts with artificial heart valves*
(Xarelto) CrCl 15-50: 15mg QD meal Can be crushed
Inferior to warfarin, same bleeding risk
Apixaban Oral 5mg BID Bleeding Superior to warfarin, decreased
(Eliquis) 2.5 mg BID if has any bleeding risk
2: Age ≥80, Scr ≥2.5,
or weight ≤60kg
Edoxaban Oral 60mg QD Rash, abnormal LFTs, Non-inferior to warfarin, decreased
(Savaysa) Avoid if CrCl <15/ >95 bleeding bleeding risk
CrCl 15-50: 30mg QD
Warfarin Oral INR 2-3 goal (except Multiple DDI, food, Vit K, FFP, PCC May need to bridge therapy
mech. valve) disease states Inhibits the clotting factors 2,7,9,10,
protein C & S
* If mechanical valve,
target INR greater
than 2.5
* Cleared renally
 Chidiebere Eze, PharmD; Aug 20, 2017

References:
1. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: Executive
Summary. Craig T. January, L. Samuel Wann, Joseph S. Alpert, et al. Journal of the American
College of Cardiology Dec 2014, 64 (21) 2246-2280; DOI: 10.1016/j.jacc.2014.03.021
2. Lexi-Drugs. Lexi-Comp Online. Lexi-Comp, Inc. Hudson, OH. Available at:
http://online.lexi.com/crlonline. Accessed Mar 20, 2017.