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Atrial Fibrillation

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Andrew Miesner

on 7 September 2017

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Transcript of Atrial Fibrillation

• Recognize medications and other factors that may contribute to the development or exacerbation of atrial fibrillation.

• Recognize the medications that should and shouldn’t be used for conversion, for maintenance, etc

• Protect patients from drug/drug or drug/disease state interactions (CHF, WPW, concomitant QTc prolongers)

• Dosing of antiarrhythmics and anticoagulants

• Advocate for anticoagulation when appropriate (more on this next week...)

PHAR110 - Topics in Internal Medicine
Atrial Fibrillation
Andrew Miesner, PharmD, BCPS
Associate Professor of Pharmacy Practice
Drake University College of Pharmacy & Health Sciences


Atrial fibrillation (AF) is the most common arrhythmia

o One of the most common chronic diseases among Medicare beneficiaries

o Increases in prevalence with age

Direct Current Cardioversion (DCC)

o Generally only used acutely if the patient is hemodynamically unstable
- Also considered if unresponsive to medications and ongoing myocardial ischemia or acute heart failure
- Usually emergent cardioversion is not necessary if symptoms are >48hrs in duration

Supraventricular tachyarrhythmia with uncoordinated atrial activation

o Results in ineffective atrial contraction and subsequent variability in ventricular rate and filling

o >300 atrial beats per minute  120-180 ventricular beats per minute

• EKG is “irregularly irregular”

o rapid waves varying in amplitude, shape, and timing

o absence of consistent P waves

o irregular ventricular response

o Palpitations, SOB, dizziness, and possibly stroke symptoms

o Severity of disease based on effects on quality of life

o Occasionally asymptomatic

recurrent atrial fibrillation that terminates spontaneously (lasts up to 7 days, usually < 48 hours)

sustained > 7 days or requires termination by cardioversion
 -“Longstanding" persistent: lasting > 1 year with decision to adopt rhythm control strategy

persistent > 1 year or arrhythmia accepted by patient and physician and rhythm control interventions not pursued


≥ 2 episodes of atrial fibrillation

• Causes and Risks

o Structural issues (valvular heart disease, stenosis)

o Electrical conduction problems (especially Wolff-Parkinson-White)

o Pulmonary embolism

o Hypertension

o MI/Coronary artery disease

o Electrolyte abnormalities (Hypokalemia, hypomagnesemia, hypercalcemia)

o Hyperthyroidism

o Anemia

o Obesity

o Diabetes

o Obstructive sleep apnea

o Infection

o Volume depletion

o Drugs
 -Theophylline, Beta agonists, NSAIDs, sympathomimetics
 -Alcohol abuse or withdrawal, nicotine

o Etc…
• Complications

o Heart failure

o Myocardial infarction (rarely)

o Stroke and systemic embolism

Stroke is a leading cause of death in AF, but events are rare in patients with few comorbidities

Day-to-day risk <1%

Risk stratification tools: CHADS2 vs , R2CHADS2, CHA2DS2-VASc

CHA2DS2-VASc is recommended by 2014 AHA guidelines and 2010 ESC guidelines

CHA2DS2-VASc is a better predictor of stroke in lower risk individuals than previous tools

ongestive heart failure
1 point
ypertension (or if treated)
1 point
ge 75+ 2
1 point
troke or TIA 2
ascular disease (MI, PAD, aortic plaque)
1 point
ge 65-74
1 point
ategory (female)
1 point

Initial goals

o Primary: Decrease the ventricular rate to maintain hemodynamic stability
 -NOT necessarily to restore NSR

o Secondary: Prevent stroke

• General treatment approach

o Slow down the ventricular rate

o Direct current cardioversion in hemodynamically unstable patients

o Remove/treat underlying cause

• Agents – use IV route initially, switch to PO options when clinically stable

IV Beta-blockers
 -Metoprolol (most common), propranolol, esmolol (uncommon)
 -May switch to other orals
 -Use catiously if acute decompensated heart failure with reduced EF (HF-REF),

mortality benefit chronically in HF-REF (carvedilol, bisoprolol, metoprolol succinate)

IV Non-dihydropyridine calcium channel blockers
 -Diltiazem (most common), verapamil
 -Avoid in HF-REF due to increased risk of exacerbation

 -Use “total digitalizing dose” (TDD) as a load in first 24hrs for total of 1-1.5mg
(example: 0.5mg x1, then 0.25mg x2 doses… each 6 hours apart)
 -Good choice for patients with acute heart failure, good adjunct in HF-REF chronically
 -Poor monotherapy rate control agent chronically
• Adverse effects: acute digoxin toxicity, drug interactions, nausea, subtle anorexia
• Possible increase in mortality as monotherapy control agent

o If presenting with WPW… use NONE OF THESE!

 -May trigger ventricular fibrillation

 -Use Class I antiarrhythmics instead (flecanide or procainamide)


 -Loading doses for AFib or SVT are complex, may take up to a week due to long T ½

 -Good choice for patients with acute heart failure or when other agents have failed

 -Generally reserved due to ADRs

• May want to avoid chronic use if underlying lung dysfunction
o Should be proceeded by a transesophageal echocardiogram (TEE) if >48hrs in duration (if not anticoagulated)

-May show left ventricular thrombus (as well as some underlying causes)

Acute Anticoagulation

o Should be started prior to DCC if possible
 -Most important for AFib >48 hours in duration (or if unknown duration)

o LMWH or heparin initially with transition to oral anticoagulant
 -May also consider initial choice of a novel oral anticoagulant (NOAC), but less evidence to support this

o Anticoagulation should continue for at least 4 weeks after cardioversion
 -Some experts recommend long term if the patient is high risk for stroke
-May omit if <48 hours in duration
low risk for stroke

o Reduce symptoms and prevent stroke

-No benefit of strict over lenient control of heart rate

-Resting heart rate <110 bpm as long as patients remain asymptomatic

-More strict control (<80 bpm) for continued symptoms and reasonable for patients with heart failure

Favors Rate Control
Favors Rhythm Control
Older patients

History of heart failure


Coronary Artery Disease

Failure of rhythm control
Younger patients

Wolff-Parkonson-White / preexcitation

“Lone” atrial fibrillation

Severe symptoms chronically

Failure of rate control
o Bottom line:
rate control with beta-blockers and non-dihydropyridine CCBs will be used first line for a majority of patients with AFib

Agents to Maintain Sinus Rhythm

o Most agents are only modestly successful for maintaining NSR (20-70% success rate)

o All antiarrhythmics are potentially proarrythmic!
 -In general, if initiating these agents, one should first measure the QTc and be certain K+ and Mg++ are corrected

o Based on ADRs, increased hospitalization in AFib, and mortality risks (in some populations), this is less popular…
 -Often added when rate control fails to control symptoms
Class Ia
Increases mortality and arrhythmias post-MI
Increases CHF exacerbations (negative ionotrope)
Increased risk of AV block and QTc prolongation – Must be initiated inpatient
Anticholinergic effects
May increase mortality and other arrhythmias in AFib
QTc prolongation
CYP2D6, P-glycoprotein inhibition
Diarrhea is common
Class Ic
Beneficial for “pill-in-the-pocket” – PRN use for lone AFib
Increases mortality and arrhythmias post-MI
Increases CHF exacerbations
Should not be used for Aflutter
Prolongs QTc
Renally eliminated
Up to 10% of population under-metabolizes (CYP2D6)
Beneficial for “pill-in-the-pocket” – PRN use for lone AFib
Increases mortality and arrhythmias post-MI
Increases CHF exacerbations
Should not be used for Aflutter
Prolongs QTc
Up to 10% of population under-metabolizes (CYP2D6)
Inhibits p-glycoprotein and CYP2C9
Class III
Inhibits most CYP450 and p-glycoprotein
Prolongs QTc
Drug induced hepatitis, thyroid dysfunction, skin discoloration
Pulmonary fibrosis
Safe to use in CHF
Prolongs QTc
Renal elimination
Strict dosing based on CrCL and QTc - Must be initiated inpatient over 3 days with close QTc monitoring
REMS program
Safe in CHF
Increases CHF mortality, hospitalizations, and exacerbations
Increases risks for death and CHF in permanent AFib
REMS program
Increases QTc
Prolongs QTc
Renal elimination
Strict dosing based on CrCL and QTc - Must be initiated inpatient over 3 days with close QTc monitoring
May precipitate CHF exacerbations
• Strategies for continued symptoms

o Cardioversion
 -Pharmacologic generally less successful than DCC (particularly with long standing AFib)
 -Must be fully anticoagulated at least 3 weeks prior and continued at least 4 weeks after

o Catheter/AV node ablation with ventricular pacing
 -May improve quality of life if patients have failed antiarrhythmic therapy
-Significantly more effective at maintaining NSR versus antiarrhythmics over the long term

o Goal of these therapies is NOT to remove need for anticoagulation
 -Stroke risks persist… paroxysms may be asymptomatic
• Antithrombotic therapy

o One study suggests only about 51% of patients get adequate antithrombotic therapy after new-onset AFib

o Antithrombotic therapy should be considered regardless of SUBTYPE OF AFIB or RATE/RHYTHM STRATEGY

o Choice of therapy is based on stroke risk and individual patient factors

CHEST Guidelines (2012)
CHADS2 = 0  Nothing, aspirin, or aspirin + clopidogrel
CHADS = 1 and unwilling to take oral anticoagulants (other than for bleeding)  aspirin + clopidogrel
CHADS2 of 1 or greater  Oral anticoagulant
Oral anticoagulants recommended: dabigatran or warfarin

AHA Guidelines (2014)
CHA2DS2-VASc = 0  Nothing
CHA2DS2-VASc = 1  Nothing, aspirin, or oral anticoagulant
CHA2DS2-VASc = 2  Oral anticoagulant
Oral anticoagulants recommended: apixaban, dabigatran, rivaroxaban, or warfarin

Acute AFib/AFlutter
<48 hours
>48 hours or unknown
Consider acute anticoagulation prior
to cardioversion if high stroke risk
Acute anticoagulation
to cadioversion
Echocardogram (TEE)
Oral anticoagulants for 4 weeks

(unless no LV Thrombus,
CHA2DS2-VASc 0-1,
AND <48 hours)
No LV Thrombus
LV Thrombus Present
Postpone DCC
Anticoagulate 3-4 weeks
• Rate control versus rhythm control

• Rate control is a much more common approach due to adverse effects associated with rhythm control

• High rates of atrial fibrillation recurrence (more than two/thirds of patients within a year) when antiarrhythmic agents are used
• Catheter ablation is superior to pharmacologic agents in maintaining NSR

• AFFIRM Trial – no mortality or stroke difference between two strategies
• Higher hospitalization rates and adverse reactions in rhythm control arm

• A recent meta-analysis suggested a reduction in rehospitalization with rate control (NNT = 14), but a significant decrease all-cause mortality when using rhythm control in younger patients (<65)
Not a consistent finding in other trials
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