Treatment Options for Atrial Fibrillation

Rate Control versus Rhythm Control in Atrial Fibrillation

Atrial fibrillation can either be managed with rate control or rhythm control. Rate control allows the patient to remain in atrial fibrillation but controls the heart rate by slowing conduction at the AV node with various medications. The heart rate is considered to be controlled when it is between 60-80 beats per minute at rest and between 90-115 beats per minute during moderate exercise. Rhythm control allows for cardioversion back to normal rhythm either with medications or electrical shocks.

In the past, many cardiologists assumed that patients with persistent atrial fibrillation would benefit most from aggressive treatment to maintain normal sinus rhythm (i.e., rhythm control). A major study published in 2002, called the Atrial Fibrillation Follow-Up Investigation of Rhythm Control (AFFIRM), randomized patients with atrial fibrillation to either rate control or rhythm control groups and, surprisingly, found no major differences among the two groups with respect to death rates or overall morbidity. Most surprisingly, the rate of ischemic stroke for the patients in the rhythm control arm of the study was not lower (as had been expected) than for the patients in the rate control group. Based on these findings, the investigators concluded that rate control, in conjunction with anticoagulation, was equally effective as rhythm control in preventing morbidity and mortality in patients with atrial fibrillation. The major findings of the AFFIRM study have since been confirmed by other clinical trials such as the Rate Control versus Electrical Cardioversion (RACE) study.

The AFFIRM and RACE studies showed that rate control and rhythm control, eacj with chronic anticoagulation, are both acceptable approaches in patients with atrial fibrillation. The choice of strategy does depend on specific factors such as whether or not it is the patient's first episode, the presence of hemodynamic instability, and whether or not the patient has symptoms. If a patient has a first episode of atrial fibrillation and is bothered by symptoms such as palpitations or shortness of breath it is acceptable to try a strategy of rhythm control. However, if the patient does not easily convert to sinus rhythm or does not stay in sinus rhythm for a long period of time, it is acceptable to just control the patient's heart rate (rate control) since the long term chance of survival is similar with both strategies.

For additional information about the AFFIRM study, the reader is referred to the following article:

• A comparison of rate control and rhythm control in patients with atrial fibrillation. New England Journal of Medicine 2002, December 5; 347(23):1825-33.

Abstract Link:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12466506

Regardless of which treatment options are chosen for long term therapy, it will be necessary to give medications to slow the heart rate. If the patient is hypotensive (low blood pressure) or shows signs of congestive heart failure, direct current (DC) cardioversion should be done promptly. If the situation is not urgent, the heart rate can be controlled with medications such as digoxin, a beta blocker, or a calcium channel blocker. For patients with decreased heart function, digoxin and beta blockers are useful while calcium channel blockers are contraindicated. For patients with asthma or other contraindications to beta blockers, the calcium blockers may be useful as long as heart function is normal or near normal.

All patients with atrial fibrillation should be anticoagulated unless there is a definite contraindication. They are usually started on heparin and then warfarin (Coumadin) is given orally. Coumadin is given with the aim of achieving an international normalized ratio (INR) of 2 to 3.

Rate Control

As noted previously, one acceptable strategy for the management of patients with paroxysmal or persistent atrial fibrillation is to control the ventricular rate to 60-80 beats per minute at rest or 90-115 beats per minute during moderate exercise. This strategy is known as rate control.

A variety of pharmacological agents (medications) can be used to control the ventricular rate in patients with atrial fibrillation including:

• Calcium channel blockers

  • verapamil (e.g., Verelan)
  • diltiazem (e.g., Cardizem)

• Beta blockers

  • propranolol (e.g., Inderal)
  • sotalol (e.g., Betapace AF)
  • metoprolol (e.g., Lopressor)
  • atenolol (e.g., Tenormin)
  • acebutolol (e.g., Sectral)
  • esmolol (e.g., Brevibloc)
  • carvedilol (e.g., Coreg)

• Digoxin (e.g., Lanoxin)

In April 2008, Actavis Totowa LLC, the manufacturer of Digitek (digoxin tablets, USP) notified healthcare professionals of a Class I nationwide recall of the product due to the possibility that tablets with double the appropriate thickness may contain twice the approved level of active ingredient. The existence of double strength tablets poses a risk of digitalis toxicity in patients with kidney failure. Digitalis toxicity can cause nausea, vomiting, dizziness, low blood pressure, cardiac instability, and bradycardia. Patients are urged to contact their healthcare provider with any questions regarding Digitek.

• Amiodarone (e.g., Corderone)

In general, calcium channel blockers and beta blockers are the first-choice agents for rate control, however, digoxin and amiodarone may also be used. Digoxin is usually the first choice in patients with persistent atrial fibrillation with concurrent congestive heart failure or left ventricular dysfunction.

For patients with atrial fibrillation whose ventricular rate cannot be adequately controlled with medications or patients who experience adverse side-effects from these medications, an alterative strategy is atrioventricular (AV) nodal ablation with permanent implantation of a pacemaker. In general, this approach is effective in controlling the ventricular rate and usually leads to an improvement in symptoms such as decreased incidence of palpitations, shortness of breath, dizziness, and fatigue. Disadvantages of this treatment modality include:

• Need for continuous anticoagulation medications
• Lifetime dependency on a pacemaker
• Potential risks and complications associated with the surgical implantation of a pacemaker.

Rhythm Control

An alternative strategy that may be used in the management of patients with atrial fibrillation is rhythm control. The goal of rhythm control is to convert the patient from a state of atrial fibrillation back to normal sinus rhythm. Depending upon a variety of factors, rhythm control may be accomplished with either medications, a strategy known as pharmacological cardioversion, or with electrical shocks, an approach known as electrical cardioversion.

Pharmacological Cardioversion

Pharmacological agents used for conversion of patients with atrial fibrillation back to normal sinus rhythm (pharmacological cardioversion) are called antiarrhythmic medications and are classified as Vaughn-William class IC, class III, or class IA antiarrhythmics.

• Class IC Antiarrhythmics

  • propafenone (e.g., Rythmol)
  • flecainide (e.g., Tambocor)

• Class III Antiarrhythmics

  • amiodarone (e.g., Cordarone)
  • dofetilide (e.g., Tikosyn)
  • ibutilide (e.g., Covert Injection)
  • sotalol (e.g., Betapace CR)

• Class IA Antiarrhythmics

  • quinidine (e.g., Quinaglute)
  • procainamide (e.g., Pronestyl)
  • disopyramide (e.g., Norpace)

In general, the following principles apply to the use of antiarrhythmic medications for pharmacological cardioversion of atrial fibrillation:

• Pharmacological cardioversion is usually more effective for the treatment of recent-onset as compared to persistent atrial fibrillation.

• Class IC antiarrhythmics (propafenone and flecainide) are most effective for cardioversion of recent-onset atrial fibrillation but are less effective in cardioversion of persistent atrial fibrillation.

• The use of Class IC antiarrhythmics is contraindicated in patients with abnormal ventricular function or structural heart disease because of the high risk of ventricular proarrhythmia (a puzzling side-effect of antiarrhythmic medications that causes the onset of other types of arrhythmias, such as a type of ventricular tachycardia known as torsades de pointes).

• The problem of ventricular proarrhythmia is common to almost all antiarrhythmic medications with the exception of amiodarone. Amiodarone is the only antiarrhythmic drug approved by the U.S. Food and Drug Administration (FDA) that can be safely administered for pharmacological cardioversion of atrial fibrillation in patients with significant left ventricular hypertrophy.

• Quinidine, a class IA antiarrhythmic drug, has been shown to be very effective in cardioversion of patients with recent-onset atrial fibrillation, however, it is rarely used for pharmacological cardioversion because of the risk of serious adverse events, including sudden death.

More recently, several new antiarrhythmic agents have been developed that are currently under investigation for the prevention and treatment of atrial fibrillation. These newer agents include:

• Azimilide
• Dronedarone
• Serotonin 5-HT receptor antagonists

• Angiotensin-converting enzyme (ACE) inhibitors

  • trandolapril (e.g., Mavik)
  • enalapril (e.g., Vasotec)

• Angiotensin receptor blockers

  • candesartan (e.g., Atacand)
  • valsartan (e.g., Diovan)
  • irbesartan (e.g., Avalide)

• Aldosterone blockers

  • spironolactone (e.g., Aldactone)
  • eplernone (e.g., Inspra)

• Anti-inflammatory agents

  • statins (e.g., atorvastatin)
  • steroids (e.g., prednisone)

Electrical Cardioversion

Electrical cardioversion is another treatment option that may be used to revert atrial fibrillation back to normal sinus rhythm and has been available since the 1960s. Electrical cardioversion for atrial fibrillation is accomplished by delivering a direct current (DC) shock to the heart and is usually recommended for termination of atrial fibrillation that causes the patient to be hemodynamically unstable. This includes atrial fibrillation patients with hypotension, left ventricular failure, cardiogenic shock, refractory angina, and a rapid ventricular rate. If the duration of atrial fibrillation is less than 24 hours and is not associated with hemodynamic instability, pharmacological cardioversion can usually be used to restore the patient back to normal sinus rhythm.

Electrical cardioversion is performed under conscious sedation to avoid pain related to delivery of the electrical shock. The success rates of electrical cardioversion reported in the medical literature range from 70% to 90%. In general, restoration and maintenance of sinus rhythm with electrical cardioversion is more difficult to achieve in patients who have had atrial fibrillation for longer than one year. The rate of relapse of atrial fibrillation one to two years after electrical cardioversion is high unless concomitant antiarrhythmic drug therapy is instituted.

The traditional approach for cardioversion is to anticoagulate the patient with Coumadin and have the patient at therapeutic levels of Coumadin (INR levels between 2 and 3) for at least three weeks. Following this three week interval, cardioversion is attempted either with medications or by DC shock. In some cases medications are used first and DC shock is used only if the medications fail. One oral dose of propafenone (600 mg) has been effective in cardioverting patients. Flecanide (300 mg) given orally is also effective. The newer drugs include dofetilide (0.5 mg) given twice daily orally (a smaller dose is recommended for patients with renal disease). In the hospital, ibutilide may be used intravenously as may be amiodarone. In some medical centers, DC shock is used directly. After cardioversion, anticoagulation therapy is continued to prevent clot formation.

A more recent approach, especially in patients with more recent onset atrial fibrillation, is to start the patient on heparin and then perform transesophageal echocardiography to look for blood clots especially in the left atrial appendage. Transesophageal echocardiography, also known as TEE or heart scan with endoscopy, is a procedure used to evaluate the heart's function and structure through the use of sound waves.

If no clot is visualized by transesophageal echocardiography, cardioversion can then be done either with medications or with DC shock. The advantage of this approach is that it decreases the amount of time that the patient is in atrial fibrillation thus preventing dilatation of the left atrium which occurs as atrial fibrillation persists. This dilatation of the left atrium decreases the chance that the atrial fibrillation will be reverted back to sinus rhythm. After the patient is reverted back to sinus rhythm, it is important to keep the patient on anticoagulation with Coumadin for at least 3-4 months. This is to prevent blood clots which can form in the atria which are stunned from the cardioversion and also to prevent blood clots from intermittent episodes of atrial fibrillation which may occur for several months after cardioversion.