FIGURE 1.
Atrial fibrillation. The tracing demonstrates the absence of P waves (long arrow), as well as the presence of the fine f waves of atrial fibrillation (short arrows). Note the irregularity of the ventricular response, as seen from the variable R-R interval (brackets).
The ECG is the mainstay for diagnosis of atrial fibrillation (Figure 1). An irregularly irregular rhythm, inconsistent R-R interval, and absence of P waves are usually noted on the cardiac monitor or ECG. Atrial fibrillation waves (f waves), which are small, irregular waves seen as a rapid-cycle baseline fluctuation, indicate rapid atrial activity (usually between 150 and 300 beats per minute) and are the hallmark of the arrhythmia.
Atrial flutter is included in the spectrum of supraventricular arrhythmia. This rhythm disturbance is usually distinguishable by its more prominent saw-tooth wave configuration and slower atrial rates (Figure 2). Atrial fibrillation should also be distinguished from atrial tachycardia with variable atrio-ventricular block, which usually presents with an atrial rate of approximately 150 beats per minute. In this condition, the atrial rate is regular (unlike the irregular disorganized f waves of atrial fibrillation), but conduction to the ventricles is not regular. The resultant irregularly irregular rhythm may be difficult to differentiate from atrial fibrillation.
FIGURE 2.
Atrial flutter. Note the saw-tooth wave configuration, or flutter waves (arrows).
Initial Management
Initial Management of Atrial Fibrillation
| Drug | Initial dosing | Maintenance dosing | Comments | |
|---|---|---|---|---|
Calcium channel blockers
| ||||
Diltiazem (Cardizem)
|
15 to 20 mg IV over 2 minutes; may repeat in 15 minutes
|
5 to 15 mg per hour by continuous IV infusion
|
Convenient; easy to titrate to heart rate goal
| |
Verapamil (Calan, Isoptin)
|
5 to 10 mg IV over 2 minutes; may repeat in 30 minutes
|
Not standardized
|
More myocardial depression and hypotension than with diltiazem
| |
Beta blockers
| ||||
Esmolol (Brevibloc)
|
Bolus of 500 mcg per kg IV over 1 minute; may repeat in 5 minutes
|
50 to 300 mcg per kg per minute by continuous IV infusion
|
Very short-acting; easy to titrate to heart rate goal
| |
Propranolol (Inderal)
|
1 mg IV over 2 minutes; may repeat every 5 minutes to maximum of 5 mg
|
1 to 3 mg IV every 4 hours
|
Short duration of action; hence, need for repeat dosing
| |
Digoxin (Lanoxin)
|
0.25 to 0.5 mg IV; then 0.25 mg IV every 4 to 6 hours to maximum of 1 mg
|
0.125 to 0.25 mg per day IV or orally
|
Adjunctive therapy; less effective for rate control than beta blockers or calcium channel blockers
| |
IV = intravenous.
Adapted with permission from Li H, Easley A, Barrington W, Windle J. Evaluation and management of atrial fibrillation in the emergency department. Emerg Med Clin North Am 1998;16:389–403.
Compared with beta blockers and calcium channel blockers, digoxin is less effective for ventricular rate control, particularly during exercise. Digoxin is most often used as adjunctive therapy because of its slower onset of action (usually 60 minutes or more) and its weak potency as an atrioventricular node–blocking agent. It can be used when rate control during exercise is of less concern.Digoxin is a positive inotropic agent, which makes it especially useful in patients with systolic heart failure.
The calcium channel blockers diltiazem (Cardizem) and verapamil (Calan, Isoptin) are effective for initial ventricular rate control in patients with atrial fibrillation. These agents are given intravenously in bolus doses until the ventricular rate becomes slower.Dihydropyridine calcium channel blockers (e.g., nifedipine [Procardia], amlodipine [Norvasc], felodipine [Plendil], isradipine [DynaCirc], nisoldipine [Sular]), are not effective for ventricular rate control.
Doctors are men who prescribe medicines of which they know little, to cure diseases of which they know less in human beings of whom they know nothing.--Voltaire (1694-1778)
Physicians can use the “rule of 15” in administering diltiazem to patients weighing 70 kg (154 lb): first, give 15 mg intravenously over two minutes, repeat the dose in 15 minutes if necessary, and then start an intravenous infusion of 15 mg per hour; titrate the dose to control the ventricular rate (5 to 15 mg per hour). Verapamil, in a dose of 5 to 10 mg administered intravenously over two minutes and repeated in 30 minutes if needed, can also be used for initial rate control. Although all calcium channel blockers can cause hypotension, verapamil should be used with particular caution because of the possibility of prolonged hypotension as a result of the drug's relatively long duration of action.
Beta blockers such as propranolol (Inderal) and esmolol (Brevibloc) may be preferable to calcium channel blockers in patients with myocardial infarction or angina, but they should not be used in patients with asthma. As initial treatment, 1 mg of propranolol is given intravenously over two minutes; this dose can be repeated every five minutes up to a maximum of 5 mg. Maintenance dosing of propranolol is 1 to 3 mg given intravenously every four hours. Esmolol has an extremely short half-life and may be given as a continuous intravenous infusion to maintain rate control (Table 1).
Despite depressive effects on contractility (unless the ejection fraction is below 0.20), calcium channel blockers and beta blockers can be used for initial ventricular rate control in patients with heart failure. Oxygen delivery to the heart is usually much improved once the ventricular rate is controlled (less than 100 beats per minute). A slower ventricular response rate also allows more filling time for the heart and, thus, improved cardiac output. However, the benefits of long-term treatment with calcium channel blockers or beta blockers should be carefully weighed against the negative inotropic effects. Drugs for rate control can generally be stopped once sinus rhythm is restored.
Limited data suggest that combination regimens provide better rate control than any agent alone.
RESTORATION OF SINUS RHYTHM
Medical (Pharmacologic) Cardioversion
After patients with atrial fibrillation have been stabilized and the ventricular rate has been controlled, conversion to sinus rhythm is the next consideration. The decision to restore sinus rhythm should be individualized.The many reasons for not attempting pharmacologic cardioversion include duration of atrial fibrillation for more than 48 hours, recurrence of atrial fibrillation despite multiple treatment attempts, poor tolerance of antiarrhythmic agents, advanced patient age and concomitant structural disease, large size of left atrium (greater than 6 cm), and the presence of sick sinus syndrome.2 However, continued atrial fibrillation is associated with long-term complications that can best be avoided by prompt return to sustained normal sinus rhythm and correction of underlying ischemic or structural abnormality. Early successful cardioversion may also reduce the incidence of recurrent atrial fibrillation.
Medical cardioversion may be appropriate in certain situations, especially when adequate facilities and support for electrical cardioversion are not available or when patients have never been in atrial fibrillation before. Pharmacologic agents are effective in converting atrial fibrillation to sinus rhythm in about 40 percent of treated patients.
Physicians should use medical cardioversion only after careful consideration of the possibility of proarrhythmic complications, particularly in patients with structural heart disease or congestive heart failure.7 Because cardioversion can lead to systemic emboli, heparin should be given before medical cardioversion is attempted (see part II for more information on this subject). Anticoagulation with warfarin (Coumadin) should be continued for four weeks after cardioversion.
After anticoagulation is initiated, quinidine sulfate (Quinidex), flecainide (Tambocor), or propafenone (Rythmol) may be used to attempt pharmacologic conversion. The following intravenously administered drugs may also be used: dofetilide (Tikosyn), ibutilide (Corvert), procainamide, or amiodarone (Cordarone).
A recent review and a meta-analysis concluded that flecainide, ibutilide, and dofetilide were the most efficacious agents for medical conversion of atrial fibrillation, but that propafenone and quinidine were also effective. In the presence of Wolff-Parkinson-White syndrome, procainamide is the drug of choice for converting atrial fibrillation. Less evidence supports the use of disopyramide (Norpace) and amiodarone, and evidence supports a negative effect for sotalol (Betapace). However, some investigators consider amiodarone to be the most effective agent for converting to sinus rhythm in patients who do not respond to other agents.
Quinidine, disopyramide, propafenone, and sotalol have been found to be effective in maintaining sinus rhythm. One study comparing amiodarone and disopyramide found moderate evidence of efficacy for amiodarone in the maintenance of sinus rhythm.
Overall, antiarrhythmic drug selection should be individualized based on the patient's renal and hepatic function, concomitant illnesses, use of interacting medications, and underlying cardiovascular function. Because of intravenous-formulation availability and effectiveness, one drug may be used for conversion and another for maintenance therapy. Amiodarone is the recommended agent in patients with a low ejection fraction (below 0.35) or structural heart disease. Patients should be monitored closely because quinidine, propafenone, and amiodarone may increase the International Normalized Ratio when they are used with warfarin. These same drugs and verapamil raise digoxin levels, which may necessitate a decrease in the digoxin dosage.
The question of whether rate control or rhythm control should take precedence is currently being investigated in a randomized trial (Atrial Fibrillation Follow-up Investigation of Rhythm Management). A recent small study examined rate control (using diltiazem) versus rhythm control (using amiodarone) plus anticoagulation. Overall, rate control was as good as rhythm control in reducing or eliminating symptoms and in reducing hospitalization rates, but the comparative effect on stroke risk was not studied.
Electrical Cardioversion
When patients with atrial fibrillation are hemodynamically unstable (e.g., angina, hypotension) and not responding to resuscitative measures, emergency electrical cardioversion is indicated. In stable patients, elective cardioversion is performed after three weeks of warfarin therapy. To prevent thrombus formation, warfarin is continued for four weeks after cardioversion. Although the success rate for electrical cardioversion is high (90 percent), proper equipment and expertise are necessary for safe performance.If there is time and patients are conscious, sedation should be achieved before cardioversion is attempted. Synchronized external direct-current cardioversion is performed with the pads placed anteriorly and posteriorly (over the sternum and between the scapulae) at 100 joules (J). If no response occurs, the current is applied again at 200 J; if there is still no response, the current is increased to 300 J, and then to a maximum of 360 J. If patients cannot be moved, the pads can be applied over the right sternal border and left lateral chest wall.
Patients with atrial fibrillation at a ventricular rate of less than 150 beats per minute who are hemodynamically stable can be initially treated with drugs for ventricular rate control and intravenously administered heparin for anticoagulation (see part II for more information). Medical cardioversion or elective electrical cardioversion can then be considered as appropriate. Patients are usually monitored in the hospital while cardioversion is being attempted. However, one study documented positive results for emergency-department performance of cardioversion followed by direct discharge of hemodynamically stable patients without congestive heart failure.
An alternative approach for achieving earlier return to sinus rhythm is early electrical cardioversion and the use of transesophageal echocardiography according to American Heart Association guidelines. Transesophageal echocardiography is used to detect thrombi in the right atrium. If no thrombi are present, electrical cardioversion can be performed immediately; if thrombi are detected, cardioversion can be delayed until patients have undergone three weeks of oral anticoagulation using warfarin. One recent comparative study found no differences in thromboembolic complications between conventional treatment and early cardioversion following transesophageal echocardiography.
Because of the risk of complications such as heart failure and embolic stroke, restoration of sinus rhythm is thought to be preferable to allowing atrial fibrillation to continue. However, restoration of sinus rhythm is not always possible. In elderly patients with longstanding atrial fibrillation, repeated attempts at cardioversion may be counterproductive. The chances of reverting to and maintaining sinus rhythm are lower with longer duration of atrial fibrillation and decrease to particularly low levels when atrial fibrillation has been present for more than one year. When cardioversion is inappropriate or unsuccessful, medication should be used for ventricular rate control, and anticoagulation therapy should be considered.
General recommendations for the initial management of atrial fibrillation are summarized in Table 2
TABLE 2
General Recommendations for Initial Management of Atrial Fibrillation
Acute control of the ventricular rate is best achieved with an intravenously administered calcium channel blocker (e.g., diltiazem [Cardizem]) or beta blocker (e.g., esmolol [Brevibloc]).
|
Immediate electrical cardioversion should be considered in hemodynamically unstable patients with atrial fibrillation.
|
Medical (pharmacologic) or electrical cardioversion following anticoagulation should be considered in hemodynamically stable patients with atrial fibrillation.
|
Elective electrical cardioversion should be used in patients with persistent or recurrent atrial fibrillation. The success rate for electrical cardioversion is 90%.
|
Medical cardioversion is a convenient and reasonable alternative in some patients, but it does not always terminate atrial fibrillation. The success rate for medical cardioversion is about 40%.
|
Early cardioversion after transesophageal echocardiography with intravenous anticoagulation is an increasingly used alternative strategy.
|
Information from references 2, 3, 7, 8, and 22.
REFERENCES
show all references
1. Ellenbogen KA, Wood MA, Stambler BS. Intravenous therapy for atrial fibrillation: more choices, more questions, more trials. Am Heart J. 1999;137:992–5....
2. Podrid PJ. Atrial fibrillation in the elderly. Cardiol Clin. 1999;17:173–88,ix–x.
3. Li H, Easley A, Barrington W, Windle J. Evaluation and management of atrial fibrillation in the emergency department. Emerg Med Clin North Am. 1998;16:389–403.
4. Management of new onset atrial fibrillation. Evid Rep Technol Assess (Summ). 2000;(12):1–7.
5. Wagner GS, Marriott HJ. Marriott's Practical electrocardiography. 10th ed. Philadelphia: Lippincott Williams & Wilkins, 2001:302–11.
6. Pritchett EL. Management of atrial fibrillation. N Engl J Med. 1992;326:1264–71.
7. Prystowsky EN, Benson DW Jr, Fuster V, Hart RG, Kay GN, Myerburg RJ, et al. Management of patients with atrial fibrillation. A statement for healthcare professionals. From the Subcommittee on Electrocardiography and Electrophysiology, American Heart Association. Circulation. 1996;93:1262–77.
8. Falk RH. Atrial fibrillation. N Engl J Med. 2001;344:1067–78.
9. Ergene U, Ergene O, Fowler J, Kinay O, Cete Y, Oktay C, et al. Must antidysrhythmic agents be given to all patients with new-onset atrial fibrillation?. Am J Emerg Med. 1999;17:659–62.
10. Noc M, Stajer D, Horvat M. Intravenous amiodarone versus verapamil for acute conversion of paroxysmal atrial fibrillation to sinus rhythm. Am J Cardiol. 1990;65:679–80.
11. Schreck DM, Rivera AR, Tricarico VJ. Emergency management of atrial fibrillation and flutter: intravenous diltiazem versus intravenous digoxin. Ann Emerg Med. 1997;29:135–40.
12. Segal JB, McNamara RL, Miller MR, Kim N, Goodman SN, Powe NR, et al. The evidence regarding the drugs used for ventricular rate control. J Fam Pract. 2000;49:47–59.
13. Falk RH, Leavitt JI. Digoxin for atrial fibrillation: a drug whose time has gone?. Ann Intern Med. 1991;114:573–5.
14. Rich MW. Heart failure. Cardiol Clin. 1999;17:123–35.
15. Farshi R, Kistner D, Sarma JS, Longmate JA, Singh BN. Ventricular rate control in chronic atrial fibrillation during daily activity and programmed exercise: a crossover open-label study of five drug regimens. J Am Coll Cardiol. 1999;33:304–10.
16. Masoudi FA, Goldschlager N. The medical management of atrial fibrillation. Cardiol Clin. 1997;15:689–719.
17. Miller MR, McNamara RL, Segal JB, Kim N, Robinson KA, Goodman SN, et al. Efficacy of agents for pharmacologic conversion of atrial fibrillation and subsequent maintenance of sinus rhythm: a meta-analysis of clinical trials. J Fam Pract. 2000;49:1033–46.
18. Wyse DG. The AFFIRM trial: main trial and sub-studies—what can we expect?. J Interv Card Electrophysiol. 2000;4(suppl 1):171–6.
19. Hohnloser SH, Kuck KH, Lilienthal J. Rhythm or rate control in atrial fibrillation—Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomised trial. Lancet. 2000;356:1789–94.
20. Michael JA, Stiell IG, Agarwal S, Mandavia DP. Cardioversion of paroxysmal atrial fibrillation in the emergency department. Ann Emerg Med. 1999;33:379–87.
21. Camm AJ. Atrial fibrillation: is there a role for low-molecular-weight heparin?. Clin Cardiol. 2001;24(3 suppl):I15–9.
22. Klein AL, Grimm RA, Murray RD, Apperson-Hansen C, Asinger RW, Black IW, et al. Use of transesophageal echocardiography to guide cardioversion in patients with atrial fibrillation. N Engl J Med. 2001;344:1411–20.
Members of various family practice departments develop articles for “Practical Therapeutics.” This article is one in a series coordinated by the Department of Family Medicine at the Medical University of South Carolina. Guest editor of the series is William J. Hueston, M.D.
Atrial fibrillation is the most common sustained arrhythmia encountered in the primary care setting. Approximately 4 percent of persons in the general U.S. population have permanent or intermittent atrial fibrillation, and the prevalence of the arrhythmia increases to 9 percent in persons older than 60 years. Atrial fibrillation can result in serious complications, including congestive heart failure, myocardial infarction, and thromboembolism. Recognition and acute management of atrial fibrillation in the physician's office or emergency department are important in preventing adverse consequences.
The diagnosis of atrial fibrillation should be considered in elderly patients who present with complaints of shortness of breath, dizziness, or palpitations. The arrhythmia should also be suspected in patients with acute fatigue or exacerbation of congestive heart failure.3 In some patients, atrial fibrillation may be identified on the basis of an irregularly irregular pulse or an electrocardiogram (ECG) obtained for the evaluation of another condition.
Cardiac conditions commonly associated with the development of atrial fibrillation include rheumatic mitral valve disease, coronary artery disease, congestive heart failure, and hypertension. Non-cardiac conditions that can predispose patients to develop atrial fibrillation include hyperthyroidism, hypoxia, alcohol intoxication, and surgery.
The ECG is the mainstay for diagnosis of atrial fibrillation (Figure 1). An irregularly irregular rhythm, inconsistent R-R interval, and absence of P waves are usually noted on the cardiac monitor or ECG. Atrial fibrillation waves (f waves), which are small, irregular waves seen as a rapid-cycle baseline fluctuation, indicate rapid atrial activity (usually between 150 and 300 beats per minute) and are the hallmark of the arrhythmia.
Acute Management of Atrial Fibrillation: Part II. Prevention of Thromboembolic Complications
Although comorbid conditions such as hypertension and vascular disease are factors, the predominant cause of strokes in patients with atrial fibrillation is embolization of a clot from the left atrium. When evaluated using trans esophageal echocardiography, up to 30 percent of patients with atrial fibrillation and embolic stroke are found to have atrial thrombi within 72 hours of the stroke.3,4 Risk factors for stroke in patients with atrial fibrillation include a history of transient ischemic attack or stroke, age greater than 65 years, a history of hypertension, the presence of a prosthetic heart valve (mechanical or tissue), rheumatic heart disease, left ventricular systolic dysfunction, or diabetes.
Most atrial fibrillation–derived strokes occur within the first 72 hours after medical (pharmacologic) or electrical cardio version. The risk of stroke is significant for both rhythm conversion methods and is presumed to be due to the presence of left atrial thrombi at the time of cardio version, rather than to the method used.2 These data offer compelling support for the use of antithrombotic therapy with heparin, warfarin (Coumadin), or aspirin in patients with atrial fibrillation, unless specific contraindications exist.
Heparin should not be used in patients with signs of active bleeding. In addition, its use in patients with acute embolic stroke is controversial and should be guided by the results of trans-esophageal echocardiography to detect atrial thrombi.6
In patients with atrial fibrillation that has persisted for more than 48 hours, heparin can be used to reduce the risk of thrombus formation and embolization until the warfarin level is therapeutic or cardioversion is performed. Prevention of deep venous thrombosis and pulmonary embolism are potential added benefits of initial anticoagulation with heparin.
Low-molecular-weight heparins such as enoxaparin (Lovenox) and dalteparin (Fragmin) have not been studied extensively in patients with atrial fibrillation. However, low-molecular-weight heparin are easier to use than standard unfractionated heparin, and anticoagulation with these agents may facilitate early hospital discharge. Studies are currently being performed to evaluate anticoagulation with low-molecular-weight heparins before and after cardioversion in patients with atrial fibrillation.7
Warfarin therapy is monitored using the International Normalized Ratio (INR), which is derived from the pro-thrombin time. Treatment is challenging because of the narrow therapeutic window for efficacy and the risk of major bleeding (e.g., intracranial hemorrhage). Therefore, it is important to consider risk versus benefit before warfarin is prescribed. Risk factors for major bleeding include poorly controlled hypertension, propensity for falling, dietary factors, interactions with concomitant medications, and difficulty controlling the degree of anticoagulation because of patient noncompliance.9,10 To ensure efficacy and minimize harm, the INR should be kept between 2.0 and 3.0.
If the duration of atrial fibrillation exceeds 48 hours or is unknown, transesophageal echocardiography (to rule out atrial thrombi) followed by early cardioversion is a clinically effective strategy.6,9,13 Heparin therapy should be instituted during transesophageal echocardiography. If no atrial thrombi are observed, cardioversion can be performed. If atrial thrombi are detected, cardioversion should be delayed and anticoagulation continued. To decrease the risk of thrombus extension, heparin should be continued, and warfarin therapy should be initiated. Once the INR is above 2.0, heparin can be discontinued, but warfarin should be continued for four weeks (Table 1).2,9,10
If cardio version is unsuccessful and patients remain in atrial fibrillation, warfarin or aspirin may be considered for long-term prevention of stroke.
If atrial fibrillation recurs or patients are at high risk for recurrent atrial fibrillation, warfarin may be continued indefinitely, or aspirin therapy may be considered. Factors that increase the risk of recurrent atrial fibrillation include an enlarged left atrium and left ventricular dysfunction.
Long–term anticoagulation therapy should be considered in patients with persistent atrial fibrillation who have failed cardio version and in patients who are not candidates for medical or electrical cardio version. Patients with a significant risk of falling, a history of noncompliance, active bleeding, or poorly controlled hypertension should not receive long-term anticoagulation therapy because of the high risk of bleeding complications.
Several studies 2,14,15 have evaluated the effects of aspirin, warfarin, and the combination of aspirin and warfarin for stroke prevention in patients with atrial fibrillation. Current recommendations for anticoagulant drug selection are based on the risk factors for stroke. Guidelines from the American College of Chest Physicians, the American Heart Association, and the Agency for Healthcare Research and Quality suggest that patients at highest risk for future stroke should receive warfarin and that patients at lowest risk should receive aspirin (Table 2).2,9,10
Factors that significantly increase the risk for stroke include previous stroke, previous transient ischemic attack or systemic embolus, hypertension, poor left ventricular systolic function, age greater than 75 years, prosthetic heart valve, and history of rheumatic mitral valve disease. With persistent atrial fibrillation, patients older than 65 years and those with diabetes are also at increased risk. The lowest risk for stroke is in patients with atrial fibrillation who are less than 65 years of age and have no history of cardiovascular disease, diabetes, or hypertension.
Overall, warfarin therapy has been shown to reduce the absolute risk of stroke by 0.8 percent per year, compared with aspirin.14 In patients with a history of stroke, warfarin reduces the absolute risk of stroke by 7 percent per year.14 In recent meta-analyses,14,15 all-cause mortality was similar in patients receiving warfarin and aspirin. A meta-analysis10 of studies involving patients with atrial fibrillation but no history of stroke found that warfarin would prevent 30 strokes at the expense of six additional major bleeding episodes. Aspirin would prevent 17 strokes without increasing the incidence of major hemorrhage. No difference in mortality was found for anticoagulation with aspirin or warfarin.10
Evidence on stroke prevention using combined low-dose warfarin and aspirin or using low-molecular-weight heparin has been inconclusive. Combination therapy is not currently recommended.10
The price of stroke prevention is an added risk of major bleeding and intracranial hemorrhage. Compared with aspirin, warfarin is associated with a 0.3 percent increase in the risk of major bleeding and a 0.9 percent increase in the risk of intracranial hemorrhage.14 The risk of major bleeding increases dramatically with age over 75 years and when the INR is above 4.0. Blood pressure control (i.e., maintaining systolic pressure below 160 mm Hg) is imperative to reducing the risk of intracranial hemorrhage in patients taking warfarin.9
General recommendations for anticoagulation in patients with atrial fibrillation are summarized in Table 3.2,9,10
Atrial fibrillation is the arrhythmia most commonly encountered in family practice. Serious complications can include congestive heart failure, myocardial infarction, and thromboembolism. Initial treatment is directed at controlling the ventricular rate, most often with a calcium channel blocker, a beta blocker, or digoxin. Medical or electrical cardioversion to restore sinus rhythm is the next step in patients who remain in atrial fibrillation. Heparin should be administered to hospitalized patients undergoing medical or electrical cardioversion. Anticoagulation with warfarin should be used for three weeks before elective cardioversion and continued for four weeks after cardioversion.
The recommendations provided in this two-part article are consistent with guidelines published by the American Heart Association and the Agency for Healthcare Research and Quality.
In recent years, management strategies for atrial fibrillation have expanded significantly, and new drugs for ventricular rate control and rhythm conversion have been introduced.1–3 Family physicians have the challenge of keeping current with recommendations on heart rate control, antiarrhythmic drug therapy, cardioversion, and antithrombotic therapy.The recommendations provided in this two-part article are consistent with guidelines published by the American Heart Association and the Agency for Healthcare Research and Quality.
Atrial fibrillation is the most common sustained arrhythmia encountered in the primary care setting. Approximately 4 percent of persons in the general U.S. population have permanent or intermittent atrial fibrillation, and the prevalence of the arrhythmia increases to 9 percent in persons older than 60 years. Atrial fibrillation can result in serious complications, including congestive heart failure, myocardial infarction, and thromboembolism. Recognition and acute management of atrial fibrillation in the physician's office or emergency department are important in preventing adverse consequences.
Diagnosis
Cardiac conditions commonly associated with the development of atrial fibrillation include rheumatic mitral valve disease, coronary artery disease, congestive heart failure, and hypertension. Non-cardiac conditions that can predispose patients to develop atrial fibrillation include hyperthyroidism, hypoxia, alcohol intoxication, and surgery.
The ECG is the mainstay for diagnosis of atrial fibrillation (Figure 1). An irregularly irregular rhythm, inconsistent R-R interval, and absence of P waves are usually noted on the cardiac monitor or ECG. Atrial fibrillation waves (f waves), which are small, irregular waves seen as a rapid-cycle baseline fluctuation, indicate rapid atrial activity (usually between 150 and 300 beats per minute) and are the hallmark of the arrhythmia.
Acute Management of Atrial Fibrillation: Part II. Prevention of Thromboembolic Complications
Family physicians should be familiar with the acute management of atrial fibrillation and the initiation of chronic therapy for this common arrhythmia. Initial management should include hemodynamic stabilization, rate control, restoration of sinus rhythm, and initiation of antithrombotic therapy. Part II of this two-part article focuses on the prevention of thromboembolic complications using anticoagulation. Heparin is routinely administered before medical or electrical cardio version. Warfarin is used in patients with persistent atrial fibrillation who are at higher risk for thromboembolic complications because of advanced age, history of coronary artery disease or stroke, or presence of left-sided heart failure. Aspirin is preferred in patients at low risk for thromboembolic complications and patients with a high risk for falls, a history of noncompliance, active bleeding, or poorly controlled hypertension. The recommendations provided in this article are consistent with guidelines published by the American Heart Association and the Agency for Healthcare Research and Quality.
Atrial fibrillation is the underlying cause of 30,000 to 40,000 embolic strokes per year in the United States.1 The incidence of these strokes increases with age, rising from 1.5 percent in patients aged 50 to 59 years to 23.5 percent in patients aged 80 to 89 years.2Although comorbid conditions such as hypertension and vascular disease are factors, the predominant cause of strokes in patients with atrial fibrillation is embolization of a clot from the left atrium. When evaluated using trans esophageal echocardiography, up to 30 percent of patients with atrial fibrillation and embolic stroke are found to have atrial thrombi within 72 hours of the stroke.3,4 Risk factors for stroke in patients with atrial fibrillation include a history of transient ischemic attack or stroke, age greater than 65 years, a history of hypertension, the presence of a prosthetic heart valve (mechanical or tissue), rheumatic heart disease, left ventricular systolic dysfunction, or diabetes.
Most atrial fibrillation–derived strokes occur within the first 72 hours after medical (pharmacologic) or electrical cardio version. The risk of stroke is significant for both rhythm conversion methods and is presumed to be due to the presence of left atrial thrombi at the time of cardio version, rather than to the method used.2 These data offer compelling support for the use of antithrombotic therapy with heparin, warfarin (Coumadin), or aspirin in patients with atrial fibrillation, unless specific contraindications exist.
Anticoagulant Drugs
HEPARIN
Heparin is the preferred agent for initial anticoagulation because it provides almost immediate effects and can be discontinued rapidly if bleeding complications arise.5 The drug should be given as a continuous intravenous infusion, with the dose titrated to achieve an activated partial thromboplastin time of 1.5 to 2.5 times the baseline value.Heparin should not be used in patients with signs of active bleeding. In addition, its use in patients with acute embolic stroke is controversial and should be guided by the results of trans-esophageal echocardiography to detect atrial thrombi.6
In patients with atrial fibrillation that has persisted for more than 48 hours, heparin can be used to reduce the risk of thrombus formation and embolization until the warfarin level is therapeutic or cardioversion is performed. Prevention of deep venous thrombosis and pulmonary embolism are potential added benefits of initial anticoagulation with heparin.
Low-molecular-weight heparins such as enoxaparin (Lovenox) and dalteparin (Fragmin) have not been studied extensively in patients with atrial fibrillation. However, low-molecular-weight heparin are easier to use than standard unfractionated heparin, and anticoagulation with these agents may facilitate early hospital discharge. Studies are currently being performed to evaluate anticoagulation with low-molecular-weight heparins before and after cardioversion in patients with atrial fibrillation.7
WARFARIN
Chronic warfarin therapy is commonly used to prevent thromboembolic complications in patients with atrial fibrillation. Warfarin acts by inhibiting the production of vitamin K–dependent clotting factors, thereby prolonging the prothrombin time.8Warfarin therapy is monitored using the International Normalized Ratio (INR), which is derived from the pro-thrombin time. Treatment is challenging because of the narrow therapeutic window for efficacy and the risk of major bleeding (e.g., intracranial hemorrhage). Therefore, it is important to consider risk versus benefit before warfarin is prescribed. Risk factors for major bleeding include poorly controlled hypertension, propensity for falling, dietary factors, interactions with concomitant medications, and difficulty controlling the degree of anticoagulation because of patient noncompliance.9,10 To ensure efficacy and minimize harm, the INR should be kept between 2.0 and 3.0.
ASPIRIN
If bleeding risk prohibits the use of warfarin, aspirin is an appropriate alternative. Aspirin acts to inhibit platelet aggregation and thrombus formation by irreversibly inhibiting the production of cyclooxygenase and thromboxane.11 Compared with warfarin, aspirin is slightly less effective in preventing stroke in patients with atrial fibrillation, but it is safer in patients at high risk for bleeding.12OTHER ANTIPLATELET AGENTS
Other antiplatelet agents, such as ticlopidine (Ticlid), clopidogrel (Plavix), and the combination of aspirin and extended-release dipyridamole (Aggrenox), have not been studied in the prevention of embolic strokes in patients with atrial fibrillation. Hence, they are not recommended for use in these patients.Anticoagulation During Cardioversion
EARLY CARDIOVERSION
Early medical or electrical cardioversion may be instituted without prior anticoagulation therapy when atrial fibrillation has been present for less than 48 hours. No specific data suggest significant benefit for heparin therapy in the first 48 hours of atrial fibrillation; however, heparin is routinely used.6If the duration of atrial fibrillation exceeds 48 hours or is unknown, transesophageal echocardiography (to rule out atrial thrombi) followed by early cardioversion is a clinically effective strategy.6,9,13 Heparin therapy should be instituted during transesophageal echocardiography. If no atrial thrombi are observed, cardioversion can be performed. If atrial thrombi are detected, cardioversion should be delayed and anticoagulation continued. To decrease the risk of thrombus extension, heparin should be continued, and warfarin therapy should be initiated. Once the INR is above 2.0, heparin can be discontinued, but warfarin should be continued for four weeks (Table 1).2,9,10
TABLE 1
Recommendations for Antithrombotic Therapy in Cardioversion for Atrial Fibrillation
| Timing of cardioversion | Anticoagulation |
|---|---|
Early cardioversion* in patients with atrial fibrillation for less than 48 hours
|
Heparin during cardioversion period to achieve PTT of 1.5 to2.5 times the baseline value
|
Early cardioversion* in patients with atrial fibrillation for more than 48 hours or an unknown duration, but without documented atrial thrombi
|
Heparin during cardioversion period to achieve PTT of 1.5 to 2.5 times the baseline value
|
Warfarin (Coumadin) for 4 weeks after cardioversion to achieve target INR of 2.5 (range: 2.0 to 3.0)
| |
Elective cardioversion in patients with atrial fibrillation for more than 48 hours or an unknown duration
|
Warfarin for 3 weeks before and 4 weeks after cardioversion to achieve target INR of 2.5 (range: 2.0 to 3.0)
|
PTT = partial thromboplastin time; INR = International Normalized Ratio.
*—Electrical or medical (pharmacologic) cardioversion.
Information from references 2, 9, and 10.
TABLE 2
Recommendations for Antithrombotic Therapy in Chronic Atrial Fibrillation
| Stroke risk | Anticoagulation | |
|---|---|---|
High risk
|
Warfarin (Coumadin) to achieve target INR of 2.5 (range: 2.0 to 3.0)
| |
Previous stroke, transient ischemic attack, or systemic embolus
| ||
History of hypertension
| ||
Poor left ventricular systolic function
| ||
Patient age > 75 years
| ||
Rheumatic mitral valve disease
| ||
Prosthetic heart valve
| ||
Moderate risk
|
One risk factor: warfarin to achieve target INR of 2.5 (range: 2.0 to 3.0), or aspirin (325 mg per day)
| |
Patient age 65 to 75 years
|
More than one risk factor: warfarin
| |
Diabetes mellitus
| ||
Coronary artery disease with preserved left ventricular systolic function
| ||
Low risk
|
Aspirin (325 mg per day)
| |
Patient age < 65 years
| ||
Absence of cardiovascular disease
| ||
INR = International Normalized Ratio.
Information from references 2, 9, and 10.
If cardio version is unsuccessful and patients remain in atrial fibrillation, warfarin or aspirin may be considered for long-term prevention of stroke.
ELECTIVE CARDIOVERSION
Warfarin should be given for three weeks before elective electrical cardio version is performed. After successful cardio version, warfarin should be continued for four weeks to decrease the risk of new thrombus formation.2,9 Alternative approaches using low-molecular-weight heparins are under investigation.7,9If atrial fibrillation recurs or patients are at high risk for recurrent atrial fibrillation, warfarin may be continued indefinitely, or aspirin therapy may be considered. Factors that increase the risk of recurrent atrial fibrillation include an enlarged left atrium and left ventricular dysfunction.
Long-Term Anticoagulation
Several studies 2,14,15 have evaluated the effects of aspirin, warfarin, and the combination of aspirin and warfarin for stroke prevention in patients with atrial fibrillation. Current recommendations for anticoagulant drug selection are based on the risk factors for stroke. Guidelines from the American College of Chest Physicians, the American Heart Association, and the Agency for Healthcare Research and Quality suggest that patients at highest risk for future stroke should receive warfarin and that patients at lowest risk should receive aspirin (Table 2).2,9,10
Factors that significantly increase the risk for stroke include previous stroke, previous transient ischemic attack or systemic embolus, hypertension, poor left ventricular systolic function, age greater than 75 years, prosthetic heart valve, and history of rheumatic mitral valve disease. With persistent atrial fibrillation, patients older than 65 years and those with diabetes are also at increased risk. The lowest risk for stroke is in patients with atrial fibrillation who are less than 65 years of age and have no history of cardiovascular disease, diabetes, or hypertension.
Overall, warfarin therapy has been shown to reduce the absolute risk of stroke by 0.8 percent per year, compared with aspirin.14 In patients with a history of stroke, warfarin reduces the absolute risk of stroke by 7 percent per year.14 In recent meta-analyses,14,15 all-cause mortality was similar in patients receiving warfarin and aspirin. A meta-analysis10 of studies involving patients with atrial fibrillation but no history of stroke found that warfarin would prevent 30 strokes at the expense of six additional major bleeding episodes. Aspirin would prevent 17 strokes without increasing the incidence of major hemorrhage. No difference in mortality was found for anticoagulation with aspirin or warfarin.10
Evidence on stroke prevention using combined low-dose warfarin and aspirin or using low-molecular-weight heparin has been inconclusive. Combination therapy is not currently recommended.10
The price of stroke prevention is an added risk of major bleeding and intracranial hemorrhage. Compared with aspirin, warfarin is associated with a 0.3 percent increase in the risk of major bleeding and a 0.9 percent increase in the risk of intracranial hemorrhage.14 The risk of major bleeding increases dramatically with age over 75 years and when the INR is above 4.0. Blood pressure control (i.e., maintaining systolic pressure below 160 mm Hg) is imperative to reducing the risk of intracranial hemorrhage in patients taking warfarin.9
General recommendations for anticoagulation in patients with atrial fibrillation are summarized in Table 3.2,9,10
TABLE 3
General Recommendations for Anticoagulation in Atrial Fibrillation
Heparin therapy should be considered in hospitalized patients with atrial fibrillation persisting beyond 48 hours and in patients undergoing medical (pharmacologic) or electrical cardioversion.
|
Antithrombotic therapy using warfarin (Coumadin) should be given for 3 weeks before cardioversion and 4 weeks after successful cardioversion.
|
Patients with persistent or recurrent atrial fibrillation after attempted cardioversion should be given chronic warfarin or aspirin therapy for stroke prevention.
|
Warfarin is the preferred agent in patients at high risk for stroke because of previous stroke, age over 75 years, and/or poor left ventricular function.
|
Aspirin is the preferred agent in patients at low risk for stroke and in patients with a risk of falling, history of noncompliance, active bleeding, and/or poorly controlled hypertension.
|
REFERENCES
show all references
1. Masoudi FA, Goldschlager N. The medical management of atrial fibrillation. Cardiol Clin. 1997;15:689–719....
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3. Stein B, Halperin JL, Fuster V. Should patients with atrial fibrillation be anticoagulated prior to and chronically following cardioversion?. Cardiovasc Clin. 1990;21:231–47.
4. Grimm RA, Stewart WJ, Black IW, Thomas JD, Klein AL. Should all patients undergo transesophageal echocardiography before electrical cardioversion of atrial fibrillation?. J Am Coll Cardiol. 1994;23:533–41.
5. Hirsh J, Warkentin TE, Shaughnessy SG, Anand SS, Halperin JL, Raschke R, et al. Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy, and safety. Chest. 2001:119(1 suppl):S64–94.
6. Falk RH. Atrial fibrillation. N Engl J Med. 2001;344:1067–78.
7. Camm AJ. Atrial fibrillation: is there a role for low-molecular-weight heparin?. Clin Cardiol. 2001;24(3 suppl):I15–9.
8. Hirsh J, Dalen J, Anderson DR, Poller L, Bussey H, Ansell J, et al. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest. 2001:119(1 suppl):8S–21S.
9. Prystowsky EN, Benson DW Jr, Fuster V, Hart RG, Kay GN, Myerburg RJ, et al. Management of patients with atrial fibrillation. A statement for healthcare professionals. From the Subcommittee on Electrocardiography and Electrophysiology, American Heart Association. Circulation. 1996;93:1262–77.
10. Management of new onset atrial fibrillation. Evid Rep Technol Assess (Summ). 2000;(12):1–7.
11. Patrono C, Coller B, Dalen JE, FitzGerald GA, Fuster V, Gent M, et al. Platelet-active drugs: the relationships among dose, effectiveness, and side effects. Chest. 2001:119(1 suppl):S39–63.
12. Segal JB, McNamara RL, Miller MR, Kim N, Goodman SN, Powe NR, et al. Prevention of thromboembolism in atrial fibrillation. A meta-analysis of trials of anticoagulants and antiplatelet drugs. J Gen Intern Med. 2000;15:56–67.
13. Klein AL, Grimm RA, Murray RD, Apperson-Hansen C, Asinger RW, Black IW, et al. Use of transesophageal echocardiography to guide cardioversion in patients with atrial fibrillation. N Engl J Med. 2001;344:1411–20.
14. Hart RG, Benavente O, McBride R, Pearce LA. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med. 1999;131:492–501.
15. Taylor FC, Cohen H, Ebrahim S. Systematic review of long term anticoagulation or antiplatelet treatment in patients with non-rheumatic atrial fibrillation. BMJ. 2001;322:321–6.
Members of various family practice departments develop articles for “Practical Therapeutics.” This article is one in a series coordinated by the Department of Family Medicine at the Medical University of South Carolina. Guest editor of the series is William J. Hueston, M.D.
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