Atrial Fibrillation Medication

Updated: Apr 10, 2017
  • Author: Lawrence Rosenthal, MD, PhD, FACC, FHRS; Chief Editor: Jeffrey N Rottman, MD  more...
  • Print
Medication

Medication Summary

The goals of medical therapy for patients with atrial fibrillation (AF) are to maintain sinus rhythm, avoid the risk of complications (eg, stroke), and minimize symptoms. Warfarin represents the cornerstone of anticoagulant therapy for patients at moderate to high risk of thromboembolic events. Some patients may not be able to take anticoagulants because of contraindications or comorbidities.

Warfarin is associated with approximately 30% of reported anticoagulant-related errors. In an effort to improve patient safety, Schillig et al implemented an inpatient Pharmacist-Directed Anticoagulation Service (PDAS) to help patients reduce the risks associated with initiation of Coumadin when transitioning from the inpatient to the outpatient setting. This included appropriate enrollment in the anticoagulation clinic, documented inpatient-to-outpatient provider contact, documented inpatient provider-to-anticoagulation clinic communication, and patient follow-up with the anticoagulation clinic within 5 days of discharge. The results suggest PDAS may improve quality of care. [145]

In patients unable to take warfarin, the addition of clopidogrel to aspirin was shown to reduce the risk of major vascular events, especially stroke, when compared with placebo and aspirin in the ACTIVE (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) trial; however, increased risk for major hemorrhage was more prevalent in the clopidogrel plus aspirin group than the placebo and aspirin group. The ACTIVE trial studied 7554 patients with AF with the intent to determine whether adding clopidogrel to aspirin therapy would reduce the risk for acute vascular events (ie, stroke, myocardial infarction [MI], non-central nervous system [CNS] systemic embolism, or death from vascular event). [146]

In another study, among AF patients treated with concomitant aspirin and oral anticoagulation, there was also a significantly increased risk for bleeding. [55] Hospitalizations for bleeding events were also increased in those receiving this treatment combination.

Clopidogrel has been suggested to be less effective in reducing the rate of cardiovascular events in individuals who carry the loss-of-function CYP2C19 alleles. However, a 2010 study concluded that patients with acute coronary syndromes or AF respond well to clopidogrel, regardless of CYP2C19 loss-of-function carrier status. [147]

The goal of antiarrhythmic drug therapy is to reduce the duration and frequency of atrial fibrillation episodes, thus improving patient quality of life and symptoms. If successful, rhythm control can eliminate or delay the need for long-term anticoagulation with warfarin in some patients.

Several antiarrhythmic drugs are commonly used to prevent atrial fibrillation recurrence, such as quinidine, flecainide, propafenone, sotalol, and dofetilide. Other antiarrhythmic agents, such as amiodarone, are used in an off-label fashion with great clinical efficacy. Use of antiarrhythmic drugs requires caution because they are proarrhythmic. These agents can exacerbate preexisting arrhythmias and generate arrhythmia de novo. Tachyarrhythmias and bradyarrhythmias generated by these agents can be of ventricular or atrial origin. Drug-drug interactions and extracardiac side effects are common. Consultation with a cardiac electrophysiologist or knowledgeable clinician is recommended prior to antiarrhythmic drug initiation.

If maintenance of sinus rhythm is the goal, the American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Rhythm Society (HRS) have jointly developed guidelines for the long-term antiarrhythmic treatment in the maintenance of sinus rhythm. [1] These guidelines are intended to help clinicians tailor antiarrhythmic therapy on an individual basis for their patients.

The following algorithm incorporates clinical trial data on the safety and efficacy of antiarrhythmic agents:

Antiarrhythmic drug algorithm for the medical mana Antiarrhythmic drug algorithm for the medical management of sinus rhythm in patients with atrial fibrillation.

For patients with no evidence of structural heart disease, flecainide, propafenone and sotalol should be considered first-line agents, and amiodarone and dofetilide can be considered as alternative agents. Amiodarone is considered a reasonable first-line agent for patients with substantial left ventricular hypertrophy (LVH). Dofetilide and sotalol are first-line therapy for patients with coronary artery disease (CAD), and amiodarone is considered a second-line agent in this population. For patients with heart failure, amiodarone and dofetilide are first-line agents.

The Atrial arrhythmia Conversion Trial (ACT) I and the open-label ACT IV trials suggest that intravenous vernakalant hydrochloride can quickly convert recent-onset AF to sinus rhythm. This is potentially an important therapeutic option for the treatment of patients with AF seen in the emergency department, as the treatment was well tolerated. [148]

Current practice constraints mandate that clinicians carefully consider patient populations at low and acceptable risks for outpatient antiarrhythmic drug initiation. Proarrhythmia is the most common adverse effect of antiarrhythmics during the loading phase. Although the proarrhythmic effect of these drugs extends into the maintenance phase, a monitored inpatient setting is generally recommended for drug initiation, especially for those patients with structural heart disease or substantial comorbidities. Nevertheless, certain antiarrhythmic drugs have established and acceptable safety profiles when used in outpatients without structural heart disease or other risk factors.

Schmidt et al found that the use of non-aspirin nonsteroidal anti-inflammatory agents (NSAIDs) is associated with an increased risk of AF or flutter, suggesting a need to add this caution when prescribing this course of medication. [149]

Next:

Calcium Channel blockers

Class Summary

Calcium channel blockers are more effective than digoxin when given orally for long-term rate control and should be the initial drug of choice. They reduce the rate of AV nodal conduction and control ventricular response. Intravenous formulations control severe symptoms related to rapid ventricular rates in emergent situations.

Diltiazem (Cardizem)

Diltiazem is the drug of choice for rate control in many cases. During depolarization, it inhibits calcium ions from entering the slow channels or voltage-sensitive areas of vascular smooth muscle and myocardium.

Verapamil (Calan, Isoptin, Verelan)

Verapamil can diminish PVCs associated with perfusion therapy and can decrease the risk of ventricular fibrillation and ventricular tachycardia. During depolarization, verapamil inhibits calcium ions from entering the slow channels or voltage-sensitive areas of vascular smooth muscle and myocardium.

Previous
Next:

Beta-adrenergic Receptor Blockers

Class Summary

These agents slow the sinus rate and decrease AV nodal conduction. Beta-blockers now have more of a secondary role in AF rate control. Carefully monitor blood pressure.

Esmolol (Brevibloc)

Esmolol is an ultra–short-acting beta-adrenergic receptor blocker. It selectively blocks beta-1 receptors, with little or no effect on beta-2 receptor types. It is particularly useful in patients with elevated arterial pressure, especially if surgery is planned. It has been shown to reduce episodes of chest pain and clinical cardiac events compared with placebo. It can be discontinued abruptly if necessary. It is useful in patients at risk for experiencing complications from beta-blockade, particularly those with reactive airway disease, mild-to-moderate LV dysfunction, and/or peripheral vascular disease. A short half-life of 8 min allows for titration to the desired effect and quick discontinuation if needed.

Propranolol (Inderal)

Propranolol is a nonselective beta-adrenergic receptor blocker as well as a class II antiarrhythmic, with membrane-stabilizing activity that decreases the automaticity of contractions.

Atenolol (Tenormin)

Atenolol selectively blocks beta-1 receptors, with little or no effect on beta-2 types. Atenolol is excellent for use in patients at risk for experiencing complications from beta-blockade, particularly those with reactive airway disease, mild-to-moderate LV dysfunction, and/or peripheral vascular disease.

Metoprolol (Lopressor)

Metoprolol is a selective beta-1 adrenergic receptor blocker that decreases the automaticity of contractions. During intravenous administration, carefully monitor blood pressure, heart rate, and ECG.

Previous
Next:

Cardiac glycosides

Class Summary

These drugs slow AV nodal conduction primarily by increasing vagal tone. They are used primarily in the setting of AF with CHF.

Digoxin (Lanoxin)

Digoxin slows the sinus node and AV node via vagomimetic effects and is not very effective if sympathetic tone is increased. It is generally not recommended unless depressed LV function is present. Digoxin can be effective in sedentary patients (especially in those with heart failure) but requires close monitoring of drug levels and renal function. Combinations of rate-control medications (eg, a beta-blocker and digoxin) may be superior to individual agents in some patients.

Previous
Next:

Antiarrhythmics, class IA

Class Summary

Quinidine, procainamide, and disopyramide are class IA antiarrhythmic agents used to maintain sinus rhythm. Generally, start administration in the hospital because of the high risk of adverse effects. All patients treated with class IA agents should be treated concomitantly with AV nodal blocking agents. Some patients demonstrate a slowing in the atrial rate and an increase in AV conduction, with rapid ventricular rates, when treated with class IA agents alone. They are fading as first-line drugs for AF.

Quinidine (Cardioquin, Quinalan, Quinidex, Quinaglute)

Of Vaughn-Williams class IA agents, only quinidine is FDA approved for atrial fibrillation. As with all class IA agents, QRS and QTc prolongation are the main ECG manifestations. It should not be used in patients with a prolonged QTc baseline (>460 milliseconds). Quinidine has generally fallen out of favor as a first- or second-line agent for the treatment of atrial fibrillation.

Procainamide (Procanbid, Pronestyl)

Procainamide is not FDA approved for the treatment of atrial fibrillation; however, many use this agent for acute cardioversion (eg, postoperatively) and because it can be administered intravenously. Intravenous administration is useful for acute conversion, and it can subsequently be converted to an oral dose. It is a negative inotropic agent and vasodilator, and care must be taken when administering to patients with reduced LV function. It is generally considered a second-line agent.

Disopyramide (Norpace)

Disopyramide is not commonly used to treat atrial fibrillation because it has adverse anticholinergic effects and because it is a strongly negative inotropic agent, which may precipitate CHF and cardiogenic shock in patients with reduced LV function. It may be useful in vagally mediated syncope.

Previous
Next:

Antiarrhythmics, class IC

Class Summary

These agents are indicated for patients with AF and supraventricular tachycardia without structural heart disease. Given the results of the CAST I and II trials (increased mortality), class IC agents are generally not used in patients with concomitant LV dysfunction and/or CAD. The applicability of the CAST results to other populations (eg, patients without recent MI) is uncertain. Many specialists initiate class IC antiarrhythmic agents in an outpatient setting for patients with paroxysmal AF and no associated structural heart disease. Regardless, close patient follow-up is mandated, with frequent ECG monitoring or via transtelephonic monitoring for potential signs of proarrhythmia.

Propafenone (Rythmol)

It is indicated for documented life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia. It appears to be effective in the treatment of supraventricular tachycardias, including atrial fibrillation and flutter. It is not recommended in patients with less severe ventricular arrhythmias, even if symptomatic. Use it in conjunction with AV nodal blocking agents when administered to patients in atrial fibrillation, because conversion to AFL with 1:1 conduction (producing fast ventricular rates) has been noted.

Flecainide (Tambocor)

It is indicated for the treatment of paroxysmal atrial fibrillation/flutter associated with disabling symptoms and paroxysmal supraventricular tachycardias, including AV nodal reentrant tachycardia, AV reentrant tachycardia, and other supraventricular tachycardias of unspecified mechanism associated with disabling symptoms in patients without structural heart disease. It is also indicated for the prevention of documented life-threatening ventricular arrhythmias (eg, sustained ventricular tachycardia). It is not recommended in less severe ventricular arrhythmias even if patients are symptomatic. Use flecainide in conjunction with AV nodal blocking agents when given to patients in atrial fibrillation, because conversion to AFL with 1:1 conduction (producing fast ventricular rates) can occur.

Previous
Next:

Antiarrhythmics, class III

Class Summary

Currently, the class III antiarrhythmic agents sotalol and dofetilide are FDA approved for use in treating atrial arrhythmias; however, amiodarone is also used widely for maintenance of sinus rhythm in patients with AF. Dofetilide must be initiated in an inpatient setting. Sotalol is also initiated in an inpatient setting.

Amiodarone (Cordarone)

Amiodarone has antiarrhythmic effects that overlap all 4 Vaughn-Williams antiarrhythmic classes. It has a low risk of proarrhythmia, and any proarrhythmic reactions generally are delayed. It is used in patients with structural heart disease. Most clinicians are comfortable with inpatient or outpatient loading with 400 mg PO tid for 1 wk because of low proarrhythmic effect, followed by weekly reductions, with a goal of the lowest dose with desired therapeutic benefit (usual maintenance dose for atrial fibrillation is 200 mg/d). During loading, patients must be monitored for bradyarrhythmias.

Sotalol (Betapace atrial fibrillation)

Sotalol is a class III agent with beta-blocking effects. It is effective in the maintenance of sinus rhythm, even in patients with underlying structural heart disease. Inpatient loading is FDA mandated.

Dofetilide (Tikosyn)

Dofetilide is approved by the FDA for maintenance of sinus rhythm, as well as for the conversion of atrial fibrillation to sinus rhythm (approximately 50%) in patients with persistent atrial fibrillation. It has no effect on cardiac output, cardiac index, stroke volume index, or systemic vascular resistance in patients with ventricular tachycardia, mild to moderate CHF, angina, and either normal or reduced LVEF. It has not shown evidence of any negative inotropic effects.

Ibutilide (Corvert)

Ibutilide is indicated for conversion of recent-onset atrial fibrillation or atrial flutter (3 h to 90 d). It prolongs repolarization by increasing the slow inward sodium current and by blocking the delayed rectifier current with rapid onset.

Previous
Next:

Antiarrhythmic Agent, Miscellaneous

Class Summary

Dronedarone is an antiarrhythmic agent with properties belonging to all 4 Vaughn-Williams antiarrhythmic classes.

Dronedarone (Multaq)

It is indicated to reduce the risk for cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation or atrial flutter, with a recent episode of atrial fibrillation/atrial flutter and associated cardiovascular risk factors (ie, age >70 y, hypertension, diabetes, history of CVA, LAD >50 mm or LVEF <40%) who are in sinus rhythm or who will be cardioverted.

Important to note, however, is that dronedarone was found to be associated with increased mortality in patients with permanent atrial fibrillation. A recent randomized, double-blind, phase III trial, the Permanent Atrial fibriLLation Outcome Study Using Dronedarone on Top of Standard Therapy (PALLAS) study, was halted following a preliminary review that revealed that dronedarone was associated with a 2-fold rise in risk of death. Two-fold increases in 2 other endpoints, stroke and hospitalization for heart failure, were also noted when compared with placebo. Healthcare professionals are advised by the FDA not to prescribe dronedarone to patients with permanent atrial fibrillation.

Previous
Next:

Anticoagulants

Class Summary

Anticoagulants are used to prevent thromboembolic complications.

Heparin

Heparin augments the activity of antithrombin III and prevents the conversion of fibrinogen to fibrin. It does not actively lyse but is able to inhibit further thrombogenesis. It prevents reaccumulation of clot after spontaneous fibrinolysis.

Enoxaparin Sodium (Lovenox)

Enoxaparin is a low molecular weight heparin. It augments the activity of antithrombin III and prevents the conversion of fibrinogen to fibrin. It does not actively lyse but is able to inhibit further thrombogenesis. It prevents reaccumulation of clot after spontaneous fibrinolysis.

Warfarin (Coumadin)

Warfarin interferes with the hepatic synthesis of vitamin K–dependent coagulation factors. It is used for the prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders. Tailor the dose to maintain an INR of 2-3.

Dabigatran (Pradaxa)

Competitive, direct thrombin inhibitor. Thrombin enables fibrinogen conversion to fibrin during the coagulation cascade, thereby preventing thrombus development. Inhibits both free and clot-bound thrombin and thrombin-induced platelet aggregation. Indicated for prevention of stroke and thromboembolism associated with nonvalvular atrial fibrillation.

Rivaroxaban (Xarelto)

Factor Xa inhibitor indicated reduce risk of stroke and systemic embolism with nonvalvular atrial fibrillation. Dose is adjusted according to estimated creatinine clearance.

Apixaban (Eliquis)

Apixaban is a Factor Xa inhibitor that inhibits platelet activation by selectively and reversibly blocking the active site of Factor Xa without requiring a cofactor (eg, antithrombin III) for activity. It inhibits free and clot-bound Factor Xa, and prothrombinase activity. Although this agent has no direct effect on platelet aggregation, it does indirectly inhibit platelet aggregation induced by thrombin. Apixaban is indicated to reduce risk of stroke and systemic embolism associated with nonvalvular atrial fibrillation.

Edoxaban (Savaysa)

Edoxaban is a factor Xa inhibitor that inhibits platelet activation by blocking the active site of factor Xa without requiring a cofactor (eg, antithrombin III) for activity. Edoxaban is indicated to reduce the risk of stroke and systemic embolism associated with nonvalvular atrial fibrillation. Use is not recommended in patients with creatinine clearance ≥95 mL/min or ≤30 mL/min.

Previous
Next:

Antiplatelet Agents

Class Summary

Some patients may not be able to take anticoagulants such as warfarin because of contraindications or comorbidities. In patients unable to take warfarin, the addition of clopidogrel to aspirin has been shown to reduce the risk of major vascular events.

Clopidogrel (Plavix)

Clopidogrel selectively inhibits adenosine diphosphate (ADP) binding to the platelet receptor and subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. It is indicated for reduction of atherothrombotic events following recent stroke.

Aspirin (Bayer Aspirin, Ecotrin)

Aspirin irreversibly inhibits platelet aggregation by inhibiting platelet cyclooxygenase. This, in turn, inhibits conversion of arachidonic acid to PGI2 (potent vasodilator and inhibitor of platelet activation) and thromboxane A2 (potent vasoconstrictor and platelet aggregate). Platelet-inhibition lasts for the life of the cell (approximately 10 d). It may be used at a low dose to inhibit platelet aggregation and improve complications of venous stases and thrombosis. It reduces the likelihood of myocardial infarction. It is also very effective in reducing the risk of stroke. Anticoagulation with either aspirin or warfarin should be initiated for all individuals with AF, except those with lone AF or contraindications.

Previous