Atrial Fibrillation: Risks and Treatment

Pharmacy Times, January 2012 Aging Population , Volume 78, Issue 1

The treatment of atrial fibrillation focuses on restoring a normal heart rate and sinus rhythm and preventing thromboembolic events.

The treatment of atrial fibrillation focuses on restoring a normal heart rate and sinus rhythm and preventing thromboembolic events.

Atrial Fibrillation (AF)—a condition whereby electrical activity in the atria becomes chaotic, causing the atria to quiver rather than contract effectively— affects 2.2 million Americans. Those patients older than 40 years have a 25% risk of developing AF; approximately 70% of all AF patients are between the ages of 65 and 70 years.1,2 AF affects more men than women.3 Common symptoms include fatigue, poor exercise tolerance, dizziness, shortness of breath, heart palpitations, and chest pain, although many patients are asymptomatic.

The pathophysiology of AF is not fully understood, but it appears to involve other cardiovascular diseases, valvular disorders, diabetes, hypertension, excess catecholamines, hemodynamic stress, atrial ischemia, atrial inflammation, metabolic stress, alcohol consumption, and genetics. 3 AF significantly impacts mortality, doubling the risk of death. Additionally, AF’s complications include increased risk for stroke and heart failure.2

AF can result from reversible causes including hyperthyroidism, excessive alcohol use, obstructive sleep apnea, and structural heart disease (valvular disorders). 2 AF that is not linked to reversible causes is classified into 3 categories that guide treatment decision making:

• Paroxysmal AF: episodes lasting less than 7 days and terminating spontaneously (most episodes last less than 24 hours)

• Persistent AF: episodes lasting more than 7 days that may require pharmacologic or electrical intervention to terminate

• Permanent AF: episodes lasting longer than 1 year either because cardioversion had failed or because cardioversion had not been attempted3


Cardioversion is the procedure by which an abnormal heart rhythm is normalized, either through the administration of electrical shocks to the heart or by use of antiarrhythmic medication. When used alone, successful cardioversion can last anywhere from minutes to years. Approximately 50% to 75% of patients who had a cardioversion continue to have AF episodes.1

Treatment of AF employs 3 strategies— returning the heart to normal sinus rhythm, controlling heart rate, and preventing thromboembolic events. Strategies are not mutually exclusive, especially for those with permanent AF. Current guidelines recommend a heart rate control strategy for patients who are asymptomatic and a rhythm control strategy if heart rate control cannot be achieved or if symptoms persist despite adequate control of heart rate.2

Restoring Sinus Rhythm

The goal of antiarrhythmic pharmacotherapy is to reduce and/or eliminate AF. If successful, patients may not require anticoagulation therapy. Treatment consists of cardioversion and/or antiarrhythmic agents. Antiarrhythmic agents belong to several drug classes, each with different mechanisms of action. A useful clinical tool guiding treatment decision making is the Vaughan Williams classification scale for antiarrhythmic medication:

• Class I: sodium channel blockers

• Class II: beta-adrenergic blockers

• Class III: potassium channel blockers

• Class IV: calcium channel blockers

Patients’ comorbidities and structural heart damage dictate the selection of specific agents. Dronedarone is an antiarrhythmic agent with properties belonging to all 4 Vaughan Williams classes. Its mechanism of action is similar to that of amiodarone. Digoxin is a cardiac glycoside that slows the sinus node (the heart’s “pacemaker”) and the atrioventricular (AV) node—which regulates electrical activity between the atria and the ventricles— but it is not very effective when used alone.2

All antiarrhythmic agents can induce proarrhythmia, a potentially deadly condition. Common side effects for antiarrhythmic agents include bradycardia, palpitations, fatigue, dizziness, nausea and vomiting, stomach pain, constipation and diarrhea, rash, vision problems, and urinary retention.1 Up to 30% of patients on quinidine experience intolerable side effects.6

A “pill in the pocket” strategy is used for patients with occasional symptomatic recurrences of paroxysmal AF. Those with frequent recurrences are more effectively treated with daily dosing.2

Heart Rate Control

Electrical continuity is disrupted when the AV node becomes impaired, resulting in a heart rate of 100 to 175 bpm (beats per minute) compared with a normal rate of 60 to 100 bpm.8 A persistently elevated heart rate may weaken the heart over time and must be treated.1 Adequate rate control is defined as 60 to 90 bpm when resting and 90 to 115 bpm when exercising moderately. Oral beta-blockers and nondihydropyridine calcium channel blockers are first-line agents. A combination of drugs may be required to achieve adequate rate control, but in some patients, multiple agents can induce bradycardia.6

There are also surgical methods for achieving control of heart rate. Radiofrequency catheter ablation is a complex procedure whereby the heart’s electrical signals are mapped and surgeons destroy the atrial tissue that is emitting chaotic signals. Studies report success rates between 70% and 90% in the 2 months following the procedure. Patients undergoing this procedure are usually placed on antiarrhythmic agents. Some patients may have more than 1 ablation before normal rhythm is restored.6

The surgical maze is another option. During open heart surgery, surgeons make several incisions in the upper chambers to create a pattern of scar tissue. Scar tissue cannot conduct electrical activity, thereby interfering with the electrical activity causing AF.8

Preventing Thromboembolic Events

Anticoagulant agents (heparin, enoxaparin sodium, warfarin, and dabigatran) and antiplatelet agents (clopidogrel, aspirin) both reduce the risk of thromboembolism, although anticoagulation therapy with warfarin is significantly more effective than antiplatelet therapy.3 Warfarin’s major adverse effect is bleeding, and patients’ international normalized ratio (INR) levels must be periodically monitored. The clinical objective is to achieve a balance between preventing ischemic stroke and avoiding hemorrhagic complications. 6

Maximum protection against ischemic stroke is achieved with INR values between 2.0 and 3.0. When warfarin is contraindicated, the combination of aspirin and clopidogrel is used to reduce thromboembolic risk, although it is not as effective as warfarin. Aspirin plus clopidogrel increases bleeding risk significantly.2 Dabigatran prevents clotting by directly inhibiting thrombin, and its efficacy is comparable with that of warfarin, with the advantage that patients do not need INR testing and do not need to avoid foods containing vitamin K.

Final Thought

Along with treatment, patients with AF or at risk of developing AF are encouraged to make lifestyle changes, including increasing exercise, reducing alcohol consumption, eliminating tobacco products, and adhering to a healthy diet. PT

Table. Vaughn Williams Drug Classification System


Mechanism of Action




Moderately blocks the effects of sodium channels, leading to conduction impairment and prolonged repolarization of electrical signals


Used for acute cardioversion


Not commonly used (can precipitate congestive heart failure and reduce left ventricular function)


Infrequently used

Class IB

Minimally blocks sodium channels, shortening repolarization


Hypotension is common


Should be initiated in an inpatient setting, associated with increased mortality


Infrequently used

Class IC

Markedly blocks sodium channels, resulting in significant conduction impairment.

Flecainide,a propafenone,a and moricizinea

Considered first-line agents, but contraindicated in patients with coronary artery disease and those with structural heart disease

Class II

Beta-blockers slow the sinus rate and decrease atrioventricular nodal conduction

Propranolola, atenolola

Used more as second-line agents

Class III

Blocks potassium channels, resulting in prolonged repolarization

Class III agents are among the most widely used


Effective for short-term use, but its toxicity makes it a poor choice for long-term management


generally initiated in an inpatient setting


FDA mandates inpatient monitoring for initiation


Off-label use for permanent AF


Approved for recent onset AF


FDA approval pending

Class IV

Calcium channel blockers decrease calcium in cardiac muscle, resulting in decreased muscle contraction

Verapamil and diltiazem

Diltiazem is often the agent of choice, but verapamil is equally effective. Both agents are associated with improved quality of life and improved exercise tolerance

Class V

Miscellaneous agents with properties that differ from those in Classes I-IV

Eg, adenosineb

Adenosine receptor agonist agents act on receptors that mediate smooth muscle cell activity that is critical to coronary vasodilation

AF = atrial fibrillation.

aCarries a boxed warning. See product labeling for more information. bNot a complete listing of agents.

Adapted from references 2-7.

Dr. Zanni is a psychologist and health-system consultant based in Alexandria, Virginia.


1. Calkins HG, Berger R; Johns Hopkins Medicine. Atrial Fibrillation: The Latest Management Strategies. New York, NY: Remedy Health Media; 2011.

2. Callahan T, Baranowski B. Managing newly diagnosed atrial fibrillation: rate, rhythm, and risk. Cleve Clin J Med. 2011;78:258-264.

3. Rosenthal L. Atrial fibrillation. Accessed September 22, 2011.

4. Gaither J. Antidysrhythmic toxicity. Accessed October 1, 2011.

5. Moulton L. What’s new with antiarrhythmic drugs? Accessed September 28, 2011.

6. Fuster V, Rydén LE, Cannom DS, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines; European Society of Cardiology Committee for Practice Guidelines; European Heart Rhythm Association; Heart Rhythm Society. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society [erratum in: Circulation. 2007;116(6):e138]. Circulation. 2006;114:e257-354.

7. Chaudhry GM, Haffajee CI. Antiarrhythmic agents and proarrhythmia. Crit Care Med.2000;28(10)(suppl):N158-N164.

8. Mayo Clinic Staff. Atrial fibrillation. Accessed September 25, 2011.