INTRODUCTION ã…¡ Atrial fibrillation is a supraventricular arrhythmia, seen more commonly in patients older than age 70, characterized by uncoordinated electrical activation of the atria and an irregular, often rapid, ventricular response causing hemodynamic compromise. As the atria fibrillate, blood pools in the atria, and a clot may form in the atrial appendage, increasing the risk of embolic stroke. Atrial fibrillation is associated with a fivefold increased risk of stroke, and it is the most common arrhythmia. It worsens heart failure and increases mortality in patients with myocardial infarction, and is an independent risk factor for death.
Pathophysiology may be due to rapid discharges from numerous ectopic foci in the atria occur. This leads to erratic and uncoordinated atrial rhythm, (see Figure 1). Causes may include hypertension, myocardial infarction (MI), pulmonary embolism, heart failure or cardiomyopathy or valvular disease, hypersympathetic state associated with acute alcohol ingestion, pericarditis,hyperthyroidism and cardiothoracic surgery. Complications include transient ischemic attack, stroke, heart failure and thromboembolism.
ASSESSMENT
GENERAL STRATEGIES ã…¡ Base diagnosis of AF on characteristic ECG findings (irregularly irregular ventricular response and AF waves, best seen in leads V1–V3, and the augmented voltage unipolar left foot lead). If ventricular response rate is too rapid to reveal atrial activity, consider vagal maneuvers and gentle carotid sinus massage (provided there is no evidence of carotid artery disease) to slow rate and uncover any hidden fibrillatory or P waves. Perform workup for etiology (see causes) on outpatient basis if patient is tolerating rhythm well and there is no evidence of failure, ischemia, or embolization.
HISTORY ã…¡ Review for etiologic clues: (1) In younger patients, prior history of such episodes, excess intake of stimulants and alcohol, emotional stress, fever, heart murmur, and chest pain. (2) In older patients, preexisting heart disease, HTN, chest pain, dyspnea, cough, calf pain, leg edema, fever, light-headedness, near-syncope, loss of consciousness, weight loss, depression, history of heart murmur or rheumatic fever, and any prior attacks of palpitations. (3) Take careful drug history with emphasis on alcohol abuse. (4) Note any history of recurrent attacks dating from young adulthood (Wolff-Parkinson-White [WPW] syndrome), marked weight loss, concurrent depression, apathy (apathetic hyperthyroidism), or episodes of altered consciousness (sick sinus syndrome).
PHYSICAL EXAMINATION ã…¡ Check for hemodynamic state and etiologic clues (see above). Note apical pulse rate, BP, respiratory rate, jugular venous pulse, any apathetic appearance, marked weight loss, cyanosis, goiter, wheezes, friction rub, heart murmur (especially mitral), calf tenderness, asymmetric leg edema, and any signs of alcohol intoxication.
DIAGNOSIS
LABORATORY TESTS ã…¡ Check: (1) ECG for ventricular response rate (rate > 200 bpm or widening of QRS due to delta waves suggests WPW syndrome), pattern of fibrillatory waves (coarse ones = marked left atrial enlargement; fine ones = atherosclerotic and hypertensive heart diseases). (2) ECG for evidence of LV hypertrophy, and ST and T waves for evidence of ischemia, strain, digitalis effect, and pericarditis. (3) ECG after return to sinus rhythm for a shortened PR interval, delta waves, and sinus node dysfunction. (4) 24-hour Holter monitor for the episodes of bradycardia and tachycardia (sick sinus syndrome). (5) Chest X ray for heart failure, cardiomegaly, and intrapulmonary pathology. (6) Echocardiogram for evaluating suspected valvular, congenital, cardiomyopathic, and pericardial forms of heart disease. (7) TSH in the elderly with otherwise unexplained AF.MANAGEMENT
RATE CONTROL ã…¡ Acute rate control can be achieved with beta blockers and/or the calcium channel blockers verapamil and diltiazem administered either intravenously or orally, as warranted by the urgency of the clinical situation. Digoxin may be added, particularly in heart failure patients, if negative inotropic and other adverse effects of beta blockers and calcium channel blockers limit their use. Digoxin lacks negative inotropic effects, but is less effective in slowing the ventricular rate in AF, particularly when sympathetic tone is high. It is synergistic with the other AV nodal–blocking agents. Its use has been associated with increased mortality in some studies. Typically, the goal of acute rate control is to reduce the ventricular rate to less than 100/min, but the goal must be guided by the clinical situation and the adverse effects of rate control medications. See, algorithm of evaluation and treatment of atrial fibrillation (from AAFP).
STROKE PROPHYLAXIS IN ATRIAL FIBRILLATION (see section on Warfarin vs. New oral anticoagulants) ã…¡ For patients with underlying heart disease and AF duration < 48 hrs, consider immediate referral for elective cardioversion (either pharmacologic or electrical); precardioversion warfarin anticoagulation is unnecessary so long as cardioversion occurs within 48 hrs of onset. For all patients with underlying heart disease and AF of unknown duration or duration > 48 hrs, begin oral anticoagulant therapy with warfarin as early as possible, unless serious contraindication to warfarin. Prescribe adjustable-dose warfarin program that achieves PT INR 2–3.
ELECTIVE CARDIOVERSION ã…¡ For those at high risk for systemic embolization (e.g. prior embolization or stroke, systolic dysfunction, clinical CHF, significant left atrial mural thrombus, or female sex + age > 75), consider elective cardioversion. Also consider for elective cardioversion those with exercise intolerance or fatigue due to AF, intolerable symptomatic palpitations, or inability to take long-term oral anticoagulation. Screen out those with high probability of unresponsiveness or relapse (e.g., AF duration > 1 yr, marked left atrial enlargement, rheumatic etiology). Before elective cardioversion in persons with AF duration > 48 hrs, prescribe 3–4 weeks of adjusted-dose warfarin anticoagulation (to achieve PT INR 2–3). If desirable to proceed directly to elective cardioversion without waiting 3–4 weeks for oral anticoagulation, use transesophageal echocardiography (TEE) to enhance determination of stroke risk. If no thrombus is detected by TEE in left atrium or left atrial appendage, then reasonable to proceed directly to cardioversion. After cardioversion, preceded by warfarin or not, prescribe adjusted-dose warfarin for ≥ 4 weeks after restoration of sinus rhythm. After cardioversion in those with high risk of AF recurrence (e.g., marked left atrial enlargement, advanced age, high amount of energy required for cardioversion), consider chronic adjusted-dose warfarin prophylaxis, especially if patient has clinical features conferring high stroke risk. Alternatively, consider chronic antiarrhythmic treatment with low-dose amiodarone (e.g. 100–200 mg/day); monitor liver function tests and TSH level every 6 months. Refer those with frequent recurrences of AF that occur despite antiarrhythmic treatment for consideration of interventional approaches (e.g., atrial ablation, pacing, or defibrillator placement), especially if recurrences are not well tolerated hemodynamically.
CHRONIC ANTICOAGULATION ã…¡ For those with clinical characteristics that make them poor candidates for elective cardioversion (e.g., AF duration > 1 year, advanced rheumatic valvular disease, marked left atrial enlargement), consider long-term adjusted-dose warfarin anticoagulation, especially if they have clinical features predictive of high stroke risk. For AF patients with low to moderate risk of embolic stroke (i.e. no CHF or significant systolic dysfunction, no previous thromboembolism, SBP < 160 mm Hg, and age < 75), consider chronic aspirin therapy (e.g., 325 mg/day). Those with concurrent atherosclerotic risk factors are likely to benefit most. Consider chronic aspirin therapy for those who cannot take or refuse oral anticoagulation.
Warfarin vs. New oral anticoagulants. Anticoagulation is an essential part of atrial fibrillation management. It significantly reduces the risk of embolic stroke, but increases the risk of bleeding. Although the benefit of anticoagulation exceeds the risk of bleeding for most patients, discussions about stroke prevention vs. risk of bleeding remain challenging. Tools to aid in the assessment of the risks of stroke and bleeding are available and are useful in making decisions with patients about therapeutic options. For many years, the CHADS2 (congestive heart failure; hypertension; age 75 years or older; diabetes mellitus; prior stroke, transient ischemic attack, or thromboembolism [doubled]) scoring system has been used to estimate risk of stroke in patients with atrial fibrillation. Anticoagulation is recommended for patients with a CHADS2 score of 2 or more, unless a contraindication is present. More recently, the CHA2DS2-VASc (congestive heart failure; hypertension; age 75 years or older [doubled]; diabetes; prior stroke, transient ischemic attack, or thromboembolism [doubled]; vascular disease; age 65 to 74 years; sex category) scoring system (Table 1) has been recommended by the American College of Cardiology. Anticoagulation is recommended for patients with a score of at least 2 who have no contraindications. CHA2DS2-VASc significantly increases the number of patients eligible for anticoagulation compared with CHADS2.
| Table (1). CHA2DS2-VASc Risk Stratification Scores for Patients with Nonvalvular Atrial Fibrillation and Anticoagulation Recommendations | |||
|---|---|---|---|
| CHA2DS2-VASc risk factor | Score | ||
| Congestive heart failure | 1 | ||
| Hypertension | 1 | ||
| Age 75 years or older | 2 | ||
| Diabetes mellitus | 1 | ||
| Stroke/transient ischemic attack/thromboembolism | 2 | ||
| Vascular disease (prior myocardial infarction, peripheral artery disease, aortic plaque) | 1 | ||
| Age 65 to 74 years | 1 | ||
| Sex category (i.e., female sex) | 1 | ||
| Maximum score = 9 | ______ | ||
| CHA2DS2-VASc total score | Adjusted stroke rate (% per year) | Anticoagulation recommendation | |
| 0 | 0 | Consider daily low-dose aspirin | |
| 1 | 1.3 | May consider anticoagulation vs. aspirin or aspirin plus clopidogrel (Plavix) | |
| 2 | 2.2 | Recommended unless risks outweigh benefits, or there is a contraindication; options include: warfarin (Coumadin; target INR = 2 to 3); apixaban (Eliquis), 5 mg twice daily; dabigatran (Pradaxa), 150 mg twice daily; edoxaban (Savaysa), 60 mg daily; rivarobaxan (Xarelto), 20 mg daily; aspirin, 75 to 325 daily, plus clopidogrel, 75 mg daily (for patients who cannot tolerate anticoagulation) | |
| 3 | 3.2 | ||
| 4 | 4.0 | ||
| 5 | 6.7 | ||
| 6 | 9.8 | ||
| 7 | 9.6 | ||
| 8 | 6.7 | ||
| 9 | 15.2 | ||
| INR = international normalized ratio. Adapted with permission from January CT, Wann LS, Alpert JS, et al.; ACC/AHA Task Force Members. 2014 AHA/ACC/HRS guideline 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 Heart Rhythm Society |
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Similar clinical tools are available to assess anticoagulation bleeding risk. The HAS-BLED (hypertension, abnormal renal function and liver function, stroke, bleeding, labile international normalized ratio, elderly [older than 65 years], drugs and alcohol) scoring system has been well validated, with a score of 3 or more indicating that a patient has a high likelihood of hemorrhage. A tool for calculating a patient's HAS-BLED score is available at https://www.qxmd.com/calculate/calculator_106/bleeding-risk-in-atrial-fibrillation-has-bled-score.
Warfarin lowers the risk of thromboembolic events, but it has a narrow therapeutic range, multiple drug and food interactions, and requires frequent blood monitoring of the international normalized ratio. Even with optimal compliance, patients using warfarin are within the therapeutic range (2 to 3 for nonvalvular atrial fibrillation) only 55% to 66% of the time. Studies have shown that low-intensity warfarin in atrial fibrillation (international normalized ratio of approximately 1.5) is not effective in preventing stroke. Aspirin alone or in combination with clopidogrel is an option for patients who decline or are unable to tolerate anticoagulants, or who are at low risk of stroke as indicated by a CHADS2 score of 0 or 1. Direct oral anticoagulants, including a direct thrombin and several factor Xa inhibitors, are available. Their main advantages compared with warfarin include fixed dosing, no food interactions, fewer drug interactions, and no need for international normalized ratio monitoring. Their major drawbacks are higher costs, difficulty reversing their effect in emergency situations, and the lack of simple blood tests to check drug levels. A specific antidote for dabigatran is available, and factor Xa inhibitor antidotes are in the late stages of development. The oral direct thrombin inhibitor dabigatran is as effective as warfarin in preventing stroke and systemic emboli. Major bleeding events were similar to those of warfarin, with fewer intracranial bleeds, but increased gastrointestinal hemorrhage. Factor Xa inhibitors include rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa). Compared with warfarin, rivaroxaban and edoxaban are noninferior in preventing stroke and systemic thromboembolic events, although edoxaban has a lower rate of major bleeding. Apixaban is slightly superior to warfarin in stroke prevention and has a lower bleeding risk. These oral anticoagulants also have a slightly lower risk of intracranial hemorrhage compared with warfarin but require dose adjustment in patients with renal disease. (Table 2) outlines the pharmacologic properties of direct oral anticoagulants and warfarin; none are recommended for patients on hemodialysis, nor are they approved for use during pregnancy or in patients with valvular atrial fibrillation or advanced kidney disease.
| Table (2). Pharmacologic Properties of Anticoagulants Used for Prevention of Thromboembolism in Patients with Atrial Fibrillation | ||||||
|---|---|---|---|---|---|---|
| DRUG | MECHANISM | DOSING | ORAL BIOAVAILABILITY | TIME TO EFFECT (HOURS) | HALF-LIFE (HOURS) | REVERSIBLE |
| Apixaban (Eliquis)† | Factor Xa inhibitor | 5 mg twice daily 2.5 mg twice daily for patients with ≥ 2 of the following: creatinine > 1.5 mg per dL (132.60 μmol per L), age > 80 years, weight < 132 lb (60 kg) |
58% | 3 to 4 | 8 to 15 | No |
| Dabigatran (Pradaxa)‡ | Direct thrombin inhibitor | 150 mg twice daily 75 mg twice daily for CrCl 15 to 30 mL/min Not recommended if CrCl < 15 mL/min |
3% to 7% | 1 to 2 | 12 to 17 | Yes |
| Edoxaban (Savaysa)† | Factor Xa inhibitor | 60 mg daily 30 mg daily if CrCl 15 to 50 mL/min Avoid use if CrCl > 95 mL/min due to increased clearance Not recommended if CrCl < 15 mL/min Avoid in Child-Pugh Class B or C liver disease |
62% | 1 to 2 | 10 to 14 | No |
| Rivaroxaban (Xarelto)† | Factor Xa inhibitor | 20 mg daily 15 mg daily for CrCl 15 to 50 mL/min Not recommended if CrCl < 15 mL/min |
60% | 2 to 4 | 5 to 9 | No |
| Warfarin (Coumadin)§ | Vitamin K antagonist Inhibits synthesis of factors II, VII, IX, X, and proteins C and S |
Variable (dose adjusted to international normalized ratio) | 100% | 72 to 96 | 40 | Yes |
| CrCl = creatinine clearance. †—Strong P-glycoprotein inhibitors, strong cytochrome P450 inducers and inhibitors. ‡—Strong P-glycoprotein inhibitors with concomitant kidney dysfunction. §—Numerous drug interactions with various foods and supplements. Educate patients and check for interactions. |
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REFERENCES
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Gutierrez, C. and Blanchard, D.G. (2016). Diagnosis and Treatment of Atrial Fibrillation. American Family Physician, [online] 94(6), pp.442–452. Available at: https://www.aafp.org/afp/2016/0915/p442.html
Maryland, S.L., PharmD Clinical Pharmacy Specialist Kaiser Permanente Silver Spring (n.d.). Antiarrhythmic Treatment in Atrial Fibrillation. [online] www.uspharmacist.com. Available at: https://www.uspharmacist.com/article/antiarrhythmic-treatment-in-atrial-fibrillation