KAISER PERMANENTE OHIO ATRIAL FIBRILLATION Methodology: Evidence-Based Issue Date: 3-97 Champion: Cardiology Most Recent Updates: 9-03,12-05, 2-07, 1-09 Key Stakeholders: Cardiology, IM Next Update: 3-11 BACKGROUND Atrial fibrillation (AF) is associated with an increased risk of thromboembolism, especially to the brain. Two basic strategies have evolved for reducing the risk of stroke in atrial fibrillation: cardioversion and antithrombotic therapy. This discussion will center on these two basic strategies. The vast majority of patients with atrial fibrillation have organic heart disease. Less than 10% of atrial fibrillation cases are defined as lone atrial fibrillation; (i.e., patients with atrial fibrillation without organic heart disease, hypertension or diabetes mellitus). Valvular heart disease accounts for 15% to 30% of the cases of atrial fibrillation; nonvalvular heart disease accounts for 50% to 80% with causes including coronary artery disease, cardiomyopathy, congenital heart disease, hypertension, and thyrotoxic heart disease. Most patients presenting to the physician's office or to the Emergency Department with atrial fibrillation do not require hospital admission. AF not occurring in a setting of reversible cause (e.g., myocardial infarction, pericarditis and cardiac surgery) can be classified in the following categories: new-onset AF, paroxysmal AF, persistent AF, and permanent AF. 1 New-onset AF is defined as AF not previously documented. Paroxysmal AF is if the arrhythmia terminates spontaneously not dependent upon pharmacologic or nonpharmacologic interventions. The duration of the paroxysmal AF is normally less then 24 to 48 hours. Paroxysmal AF may occur only once or may be recurrent. Persistent AF is defined as AF with duration of seven days or longer. Permanent AF is defined as long standing AF in which no further attempts will be made to restore or maintain sinus rhythm. The recommendations contained in this guideline can be followed for most patients without inpatient hospitalization. Cardioversion can be performed in an outpatient monitored setting. Anticoagulation with warfarin can be initiated and followed in outpatients. Acute myocardial infarction needs to be ruled out in few patients with atrial fibrillation. When uncertainty exists, contact the Cardiologist on-call. The use of electrical cardioversion in the outpatient monitored setting can be expected to decrease hospital admissions and shorten stays in monitored areas. RECOMMENDATIONS Rhythm Control vs. Heart Rate control Reasons for restoration and maintenance of sinus rhythm in patients with AF include relief of symptoms, prevention of embolism, and avoidance of cardiomyopathy. Conversion to and maintenance of sinus rhythm offers the theoretical advantages of reducing the risk of thromboembolism and consequently the need for chronic anticoagulation. Several recently published clinical trials (AFFIRM, RACE) have been completed with data suggesting no clear advantage of one approach over the other with similar outcomes in total mortality and ischemic stroke. New-Onset Atrial Fibrillation (see Figures 1 & 2)
When atrial fibrillation duration has been less than 48 hours, no anticoagulation is required and cardioversion can be performed. Rate control with beta blockers, calcium blockers, or digoxin is suggested to obtain a resting heart rate <100 before attempted chemical cardioversion with antiarrhythmic medications such as 1A drugs (e.g., quinidine, procainamide, disopyramide), or 1C drugs (propafenone, flecainide). Type 1C drugs should not be used in patients with prior myocardial infarction or with decreased left ventricular function. Emergency direct current cardioversion for new onset atrial fibrillation should be considered in hemodynamically unstable patients or patients with congestive heart failure or myocardial infarction with rapid ventricular response. After 48 hours, or if one is uncertain as to the duration of the new onset AF, the patient should be given warfarin therapy for at least 3 to 4 weeks at an INR of 2-3 and schedule for an elective cardioversion. During this period, rate control should be established with standard therapy including digoxin, calcium channel blockers, or beta blockers (see Fig 3). Hospitalization is not required in these patients when starting warfarin therapy to establish therapeutic levels. This can be accomplished in an outpatient setting. Recurrent Paroxysmal Atrial Fibrillation (See Fig. 3) For patients who experience brief or minimally symptomatic recurrences of paroxysmal AF, it is reasonable to avoid antiarrhythmic drugs unless troublesome symptoms occurs. Rate control and prevention of thromboembolism are appropriate in both situations. Recurrent Persistent Atrial Fibrillation (See Fig. 3) Defined as patient who have undergone at least 1 attempt to restore sinus rhythm and may remain in AF after its second occurrence with minimal or no symptoms. These patients should be treated with therapy for rate control and prevention of thromboembolism. Alternatively, those with symptoms favoring sinus rhythm should be treated with an antiarrhythmic agent (in addition to medications for rate control and anticoagulation) before cardioversion. Permanent Atrial Fibrillation (See Fig. 3) The treatment of permanent AF is given to patients in which sinus rhythm cannot be sustained after cardioversion of AF or when the patient and physician have decided to allow AF to continue without further efforts to restore sinus rhythm. It is important to maintain control of the ventricular rate and to use antithrombotic therapy, as outlined in TABLE 2 for all patients in this category. Preventing Thromboembolism (See Table 1) The rate of stroke in patients with AF is related to coexistent cardiovascular disease. Adjusted-dose oral anticoagulation (Warfarin) is more efficacious then aspirin for prevention of stroke in patients with AF. All patients with AF should be administered antithrombotic therapy (Warfarin or Aspirin), except those with lone AF, to prevent thromboembolism. Those with coumadin include those with an allergy to coumadin, recent surgery (6 weeks), proten c deficiency frequent falls especially those with a history of head trauma or fracture other than hip and pregnancy. The selection of antithrombotic agent (Warfarin or Aspirin) should be individualized based upon assessment of the absolute risks of stroke and bleeding and the relative risk and benefit for the particular patient (See TABLE 2). Chronic oral anticoagulant therapy (Warfarin) should be dose adjusted to achieve a target INR of 2 to 3 in patients at high risk of stroke, unless contraindicated. Aspirin in a dose of 325 mg daily may be used as an alternative in low-risk patients or in those with certain contraindications to oral anticoagulation. Oral anticoagulation with Warfarin is indicated for all patients with AF associated with rheumatic mitral valve disease or prosthetic heart valves (mechanical or tissue valves). The use of anticoagulation in those patients age 85+ or those with severe functional impairment needs to be tempered by clinical judgment, given the known risks of anticoagulation. Adapted from KP Southern California Page 2
Cardioversion Cardioversion is usually performed electively to restore sinus rhythm in patients with persistent AF. Cardioversion without prior anticoagulation may be attempted in patients with new-onset AF less then 24 hours or when acute AF produces hemodynamic instability in the form of angina pectoris, MI, shock, or pulmonary edema. Otherwise, anticoagulation with warfarin with an INR of 2-3 is recommended for 3 to 4 weeks before and after cardioversion for patients with AF of unknown duration or with AF for more then 48 hours. Asymptomatic patients with controlled atrial fibrillation of more than 24 hours duration who are considered for cardioversion do not require hospitalization for anticoagulant therapy. They can be treated with 3 weeks of warfarin therapy with INR of 2-3. After this treatment, they may have chemical or electrical cardioversion. Rate control should be attempted with beta blockers or calcium channel blockers. Digoxin used as monotherapy is a poor drug for rate control. Underlying etiologic mechanisms for atrial fibrillation must be investigated, such as thyrotoxicosis and congestive heart failure. The role of echocardiography in atrial fibrillation is to exclude anatomic disease. When history and physical exam suggest valvular, myocardial, or pericardial disease the study is indicated. It should not be used solely to determine left atrial size, which in itself does not predict the initial success of cardioversion. Chemical Cardioversion (see Table 2) Chemical cardioversion, if preferred to electrical cardioversion, may be attempted in an electrocardiographically monitored setting. This may be emergency room, telemetry unit, or other in or outpatient monitored area. Patients without ventricular dysfunction or ischemia are at low proarrhythmic risk. Electrical cardioversion is preferred by many physicians because of the risk of proarrhythmia associated with anti-arrhythmic agents. New regimens such as single dose oral flecainide at 300 mg exist to supplement or supplant the older regimens of quinidine and procainamide. Intravenous Ibutilide is an option in patients without cardiomyopathy but requires electrocardiographic monitoring for six hours after administration. Chemical cardioversion should be successful in 24 hours or less. After cardioversion, discharge to outpatient follow-up can usually be accomplished promptly in low risk patients and within 24 hours in high risk patients. Rate control is defined as a resting ventricular rate of atrial fibrillation < 110 beats/minute. Initial therapy with usual loading dose of digoxin 0.75-1 mg followed by maintenance digoxin should be used in patients with rapid atrial fibrillation. Additional rate control should be accomplished with either beta blockers or calcium channel blockers. The calcium channel blockers most commonly used are dilitiazem or verapamil. Digoxin should not be pushed to high doses. Digoxin is not a good drug for rate control in atrial fibrillation, particularly during enhanced sympathetic states such as physical activity, because the rate control of digoxin is solely from vagotonic action. Once rate control is established, chemical cardioversion can be attempted with a 1A, 1C, or type III drug. If the patient should develop "torsade de pointes" (i.e., a rapid polymorphic ventricular tachycardia, or an exacerbation of ventricular ectopy secondary to the drug), the patient should be assessed and the drug stopped. A second drug could be tried. If chemical cardioversion with a 1A, IC or type III drug is not successful, electrical cardioversion should be attempted unless digitoxicity is suspected. In the patient with chronic atrial fibrillation, if the duration has exceeded 6 months, cardioversion is not usually recommended. A return to sinus rhythm is unlikely. Rate control should be established. Warfarin therapy should be continued for 4 weeks after successful cardioversion to normal sinus rhythm. Antiarrhythmic therapy may be continued for 6-12 months after successful conversion. Therapy should be reassessed after this time. Caution: Antiarrhythmic drugs may cause proarrhythmia and may lead to increased mortality rates. Adapted from KP Southern California Page 3
Table 1. Risk-Based Antithrombotic Therapy in Patients With Atrial Fibrillation Patient Features Recommended Antithrombotic Therapy Age < 60, no heart disease (Lone AF) Aspirin (325 mg per day) or no therapy Age < 60, heart disease but no risk factors* Aspirin (325 mg per day) Age 60, no risk factors* Aspirin (325 mg per day) Age 60, with diabetes or CAD Oral anticoagulation (INR 2.0-3.0), addition of aspirin (81-162 mg) per day is optional Age to 75, especially women Oral anticoagulation (INR = 2.0) Heart failure, LV ejection fraction 35%, Oral anticoagulation (INR 2.0-3.0) thyrotoxicosis, and hypertension Rheumatic heart disease (mitral stenosis) Oral anticoagulation (INR 2.5-3.5 or higher may be Prosthetic heart valves appropriate) Prior thromboembolism Persistent atrial thrombus on TEE * Risk factors for thromboembolism include heart failure, LV EF < 35%, history or hypertension. Table 2. Recommended Drugs for Pharmacological Cardioversion of Atrial Fibrillation Drug Route of Dosages Potential Adverse Effects Administration Amiodarone Oral Inpatient: 1.2-1.8 g per day in divided dose until 10 g total, then 200-400 mg per day maintenance or 30 mg/kg as single dose Intravenous/oral Oral Outpatient: 600-800 mg per day divided dose until 10 g total, then 200-400 mg per day maintenance 5-7 mg/kg over 30-60 min, then 1.2-1.8 g per day continuous IV or in divided oral doses until 10g total, then 200-400 mg per day maintenance Creatinine Clearance Dose (ml/min) >60 40-60 20-40 <20 (mcg BID) 500 250 125 Contraindicated Flecainide Oral 200-300 mg Intravenous 1.5-3.0 mg/kg over 10-20 min Propafenone Oral 450-600 mg Intravenous 1.5-2.0 mg/kg over 10-20 min Quinidine Oral 0.75-1.5 g in divided doses over 6-12 h, usually with a rate-slowing drug Hypotension, bradycardia, QT prolongation, tosade de pointes (rare), GI upset, constipation, phlebitis (IV) QT prolongation, torsade de pointes; adjust dose for renal function, body size, and age Hypotension, rapidly conducting atrial flutter Hypotension, rapidly conducting atrial flutter QT prolongation, tosade de pointes, GI upset, hypotension Adapted from KP Southern California Page 4
Figure 1. Treatment Algorithm New-Onset Atrial Fibrillation New-Onset AF Paroxysmal Persistent 1. No therapy needed unless severe symptoms (e.g., hypotension, HF, angina) 2. Treat associated HD Yes Accept permanent AF No as needed Consider Antiarrhythmic drug therapy Cardioversion Long-term antiarrhythmic drug therapy unnecessary * The use of anticoagulation in those patients age 85+ or those with severe functional impairment needs to be tempered by clinical judgment, given the known risks of anticoagulation. Adapted from KP Southern California Page 5
Figure 2. Antiarrythmic Drug Selection for Rhythm Heart Disease No or minimal Yes Flecainide Propafenone Sotalol CHF or LVEF < 0.35% CAD Hypertension Amiodarone, Amiodarone, Sotalol LVH 1.4 cm Yes No Disopyramide Procainamide Quinidine Amiodarone Amiodarone Flecainide Propafenone Consider nonpharmacological options, i.e. AV ablation, AV nodal ablation with permanent pacemaker, Focal RFA Disopyramide Procainamide Quinidine Amiodarone Sotalol Disopyramide Procainamide Quinidine Adapted from KP Southern California Page 6
Figure 3. Treatment Algorithm: Recurrent and Permanent Atrial Fibrillation Recurrent Paroxysmal AF Recurrent Persistent AF Permanent AF Minimal or no Symptoms Disabling symptoms in AF Minimal or no Symptoms Disabling symptoms in AF Anticoagulation No drug for prevention of AF Antiarrhythmic drug therapy Electrical cardioversion Continue anticoagulation and therapy to maintain sinus rhythm * The use of anticoagulation in those patients age 85+ or those with severe functional impairment needs to be tempered by clinical judgment, given the known risks of anticoagulation. Adapted from KP Southern California Page 7
SOURCES 1. Kaiser Permanente, Southern California. Guideline for Atrial Fibrillation 12-2000. 2. Fuster V, Ryden LE, Asinger RW, et al. ACC/AHA/ESC 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 and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the North American Society of Pacing and Electrophysiology. J Am Coll Cardiol. 2001;38:1-70. 3. Van Gelder IC, Hagens VE, et al. A Comparison of Rate Control and Rhythm Control in Patients with Recurrent Persistent Atrial Fibrillation. NEJM. 2002; 347: 1834-1840. Adapted from KP Southern California Page 8