eMedicine Specialties > Cardiology > Arrhythmias
Atrial Fibrillation: Treatment & Medication
Updated: Oct 29, 2009
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Treatment
Medical Care
Management of new-onset atrial fibrillation differs from that of long-term atrial fibrillation.
Management of New-Onset Atrial Fibrillation
The management of atrial fibrillation can be broken down into management of new-onset and long-standing atrial fibrillation. The cornerstones of new-onset atrial fibrillation management are rate control and anticoagulation.12 The clinical decision to use a rhythm control or rate control strategy requires integration of several factors, including degree of symptoms, likelihood of successful cardioversion and presence of comorbidities. Anticoagulation is an important consideration in both new onset and long-standing atrial fibrillation. See Media file 3.Patient management for newly diagnosed atrial fibrillation. Subtherapeutic INR: INR <2 for 3 consecutive weeks. Warfarin: INR target 2-3. TEE/cardioversion: low molecular weight heparin 1 mg/kg bid as a bridge with initiation of warfarin INR 2-3.
Restoration of sinus rhythm with regularization of the heart's rhythm improves cardiac hemodynamics and exercise tolerance. By maintaining the atrial contribution to cardiac output, symptoms of heart failure and overall quality of life can improve. As atrial fibrillation contributes to pathologic atrial and ventricular remodeling, restoration of sinus rhythm can slow and, in some cases, reverse atrial dilatation and left ventricular dysfunction. For these reasons, most clinicians focus initially on maintenance of sinus rhythm and opt for a rate control strategy only when rhythm control fails.
However, several randomized controlled trials have demonstrated that a strategy aimed at restoring (and maintaining) sinus rhythm neither improves the survival rate nor reduces the risk of stroke in patients with atrial fibrillation.
In the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study,13 4060 subjects aged 65 years or older whose atrial fibrillation was likely to be recurrent and who were at risk for stroke were randomized to a strategy of rhythm control (cardioversion to sinus rhythm plus drugs to maintain sinus rhythm) versus a strategy of rate control (in which no attempt was made to restore or maintain normal sinus rhythm). An insignificant trend toward increased mortality was noted in the rate control group, and, importantly, no evidence suggested that the rhythm control strategy protected patients from stroke. Clinically silent recurrences of atrial fibrillation in the rhythm control group are theorized to be responsible for the increased rates of thromboembolic events and mortality noted in this cohort. This underscores the importance of anticoagulation in both rhythm control and rate control patients.
The AFFIRM study (and similar findings from the smaller Rate Control Versus Electrical Cardioversion [RACE] trial14 ) has led to the development of consensus guidelines that recommend an initial rate-control strategy for many asymptomatic patients with atrial fibrillation. The ACC/AHA/ESC 2006 guidelines state that an initial rate control strategy is "reasonable" for asymptomatic or minimally symptomatic older patients with hypertension and comorbid cardiovascular disease.3 These same guidelines state that for younger individuals, especially those without significant comorbid cardiovascular disease, an initial rhythm control strategy may be a better approach.Rate control
Regardless of long-term strategy chosen, control of ventricular rate is a critical component of management of new-onset atrial fibrillation. The main determinants of the ventricular rate during atrial fibrillation are those intrinsic and extrinsic factors that influence atrioventricular (AV) conduction. Foremost among these are the intrinsic AV nodal conduction properties. Underlying sympathetic and parasympathetic tone also influences AV nodal conduction. Rate-controlling agents primarily act by increasing AV nodal refractoriness.
- Beta-blockers and calcium channel blockers are first-line agents for rate control in atrial fibrillation. These drugs can be administered either intravenously or orally. They are effective at rest and with exertion. Caution should be exercised in patients with reactive airway disease who are given beta-blockers.
- Digoxin can be used in the acute setting but does little to control the ventricular rate in active patients. As such, it is rarely used as monotherapy. Caution should be exercised in elderly patients and those with renal failure receiving digoxin. Digoxin is indicated in patients with heart failure and reduced LV function.
- Amiodarone has a Class IIa recommendation from the ACC/AHA/ESC for use as a rate controlling agent for patients who are intolerant of or unresponsive to other agents. Caution should be exercised in those not receiving anticoagulation as amiodarone can promote cardioversion.
Anticoagulation
Atrial fibrillation is recognized as a powerful risk factor for stroke. One of the most important considerations in the acute management of atrial fibrillation is the need for anticoagulation. Acute cardioversion for atrial fibrillation carries a risk of thromboembolism unless anticoagulation therapy is initiated prior to the procedure and continued post-procedure. Risk of thromboembolism in patients undergoing either pharmacologic or electrical cardioversion is similar. The risk of thromboembolic events is greatest when atrial fibrillation has been present for longer than 48 hours.Effective anticoagulation in patients with atrial fibrillation reduces the risk of stroke 3-fold. Patients with newly diagnosed atrial fibrillation and patients awaiting electrical cardioversion can be started on intravenous heparin (activated partial thromboplastin time [aPTT] of 45-60 s) or low molecular weight heparin (1 mg/kg bid).
Patients can be concomitantly started on warfarin in an inpatient setting while awaiting a therapeutic INR value (2-3). Many practices have developed specialized anticoagulation clinics to closely monitor INR values.Oral direct thrombin inhibitors may represent an alternative to warfarin in a higher-risk population with nonvalvular atrial fibrillation, but no agents in this class are currently approved in the United States.
In the highest-risk population (eg, atrial fibrillation with valvular heart disease or prior embolic cerebrovascular accident) bridging anticoagulation with heparins may be required in the periprocedural period.
Cardioversion
Cardioversion may be performed electively or emergently to restore sinus rhythm in patients with new-onset atrial fibrillation. Cardioversion is most successful when initiated within 7 days after to onset of atrial fibrillation. The need for cardioversion may be acute when atrial fibrillation is responsible for hypotension, heart failure, or angina.
Pharmacologic agents or direct current energy can be used to cardiovert patients with atrial fibrillation. Pharmacologic cardioversion has the advantage of not requiring sedation or anesthesia, but the major disadvantage is the risk of ventricular tachycardia and other serious arrhythmias.Long-Term Management of Atrial Fibrillation
Long-term management of atrial fibrillation is focused on reducing the likelihood of atrial fibrillation recurrence, reducing atrial fibrillation-related symptoms, control of ventricular rate, and reducing stroke risk. As discussed previously, atrial fibrillation often results from exposure to established cardiovascular risk factors. Appropriate management of these risk factors will reduce the likelihood of future atrial fibrillation and atrial fibrillation—related morbidity and mortality. Anticoagulation should be initiated for all individuals with atrial fibrillation with either aspirin or warfarin except those with "lone" atrial fibrillation or contraindications. Selection of the appropriate antithrombotic drug should be based on the risk of stroke and bleeding for a given patient. Antiarrhythmic therapy can aid in maintenance of sinus rhythm in certain patients but requires close monitoring.
Decision-making with regard to the optimal long-term strategy for atrial fibrillation management should be based on a thorough integration of patient-specific factors and likelihood of success. As a rule, younger patients with more severe symptoms and fewer comorbidities tend to derive a greater benefit from a long-term focus on rhythm control. Older patients with structural heart disease (ie, left ventricular hypertrophy, prior myocardial infarction, depressed ejection fraction, or atrial dilation) are less likely to remain in sinus and are more likely to have serious side-effects from antiarrhythmic drugs. In this cohort, most clinicians focus on long-term rhythm control.
Atrial fibrillation causes electrophysiologic and structural remodeling which, in turn, promotes future atrial fibrillation ("atrial fibrillation begets atrial fibrillation"). As such, many patients with paroxysmal atrial fibrillation will progress to persistent and permanent atrial fibrillation. The degree to which this reflects the continuing influence of underlying cardiovascular risk factors as opposed to a direct effect of atrial fibrillation is unknown. Regardless, clinicians frequently need to reevaluate their management strategies as atrial fibrillation burden and comorbidities increase with time.
Anticoagulation
The goal of long-term anticoagulation in atrial fibrillation is to reduce the risk of thromboembolism.
- Patients in atrial fibrillation have a risk of stroke or peripheral embolism that is approximately 5 times that of people in sinus rhythm.
- Recommendations for anticoagulation for patients with nonvalvular atrial fibrillation are based on a 2006 ACC/AHA/ESC task force on the management of patients with atrial fibrillation.8
A study by van Walraven et al determined that as patients with atrial fibrillation age, the relative efficacy of oral anticoagulation does not decrease, whereas the efficacy of antiplatelet therapy does appear to decrease as a patient ages.15
Rate control
As discussed previously, several trials have validated the noninferiority of an initial rate-control strategy. Many clinicians believe, however, that an attempt at a rhythm control strategy should be made in most patients. Older patients with comorbid cardiovascular disease have a lower likelihood of successful long-term rhythm control and thus these patients are often managed using a rate-control strategy. Some patients initially managed with a rhythm control strategy will experience progression to recurrent or persistent atrial fibrillation. Clinicians often switch to a rate control strategy as the atrial fibrillation burden increases.
- AV nodal blocking medications are the cornerstone of rate control in long-standing atrial fibrillation. In the absence of an accessory pathway, oral beta-blockers, nondihydropyridine calcium channel blockers, and digoxin are effective. Generally, coadministration of beta-blockers and calcium channel blockers is reserved for patients in whom adequate rate control cannot be achieved using a single agent.
- Digoxin can be effective in sedentary patients (especially in those with heart failure) but requires close monitoring of drug levels and renal function.
- In the presence of tachycardia-mediated cardiomyopathy or inadequate ventricular rate control despite drug therapy, AV nodal ablation and pacemaker implantation can be considered.
- Combinations of rate control medications (eg, beta-blocker and digoxin) may be superior to individual agents in some patients.
- Amiodarone may contribute to ventricular rate control. On the other hand, antiarrhythmia agents may organize atrial fibrillation of a slower atrial flutter that can then conduct 1:1 from atrium to ventricle. Particularly with class Ic agents, maintenance of effective AV nodal rate control is essential in most patients.
Every effort should be made to assess effectiveness of rate control both at rest and with exertion, especially in those patients who primarily experience exertional atrial fibrillation-related symptoms. Twenty-four hour Holter monitoring or exercise-treadmill testing can be helpful in evaluating heart rate variability. Adequate rate control can be defined as a heart rate of 60-80 bpm at rest and 90-115 bpm with moderate exercise.
Rhythm control
Maintenance of sinus rhythm requires treatment of cardiovascular risk factors and any underlying disorder (ie, hyperthyroidism) that may have triggered atrial fibrillation. As discussed previously, several antiarrhythmic drugs (flecainide, propafenone, dofetilide, amiodarone) have established efficacy in the pharmacologic conversion of atrial fibrillation to sinus rhythm.
A study by Doyle and Ho determined that amiodarone, as a part of a strategy to achieve sinus rhythm, appears safe and effective in patients with persistent atrial fibrillation. However, intolerable adverse effects were more common in amiodarone than placebo or rate control drug.16
Several distinct agents, most notably sotalol, are used for the long-term maintenance of sinus rhythm. Sotalol is efficacious but, like other Class III drugs, requires close monitoring of the QT interval and serum electrolytes. Unlike dofetilide and amiodarone, sotalol is contraindicated in patients with structural heart disease and heart failure.
Catheter ablation is a reasonable alternative to pharmacologic therapy to prevent recurrent atrial fibrillation in symptomatic patients with little or no structural heart disease.17 Catheter ablation is currently being performed in select centers for persistent atrial fibrillation but this has not been established as standard of care. Surgical ablation of atrial fibrillation is also an option for patients with atrial fibrillation undergoing other cardiac surgery and in those patients in whom pharmacologic and catheter-based procedures are ineffective or contraindicated. Atrial fibrillation ablation may be superior to AV nodal ablation and biventricular pacing in heart failure patients but is technically difficult and demanding, and the widespread applicability of ablation in this population of patients is uncertain.
New medical and device-based rhythm control therapies are being actively explored. Experimental and clinical data suggest that renin-angiotensin system (RAS) antagonists and HMG-CoA-Reductase Inhibitors (statins) may decrease the incidence of atrial fibrillation and increase the likelihood of successful cardioversion.18,19,20,21 Device-based therapies under research include single- and dual-site atrial pacemakers to prevent atrial fibrillation and atrial defibrillators to rapidly restore sinus rhythm. Invasive (surgical and catheter-based) therapies to compartmentalize the atria and localize focal triggers (in the pulmonary veins) are being evaluated and refined. (See Surgical Care.)
Special considerations
Postoperative atrial fibrillation is common and perioperative beta-blockers are recommended in all patients undergoing cardiac surgery unless contraindicated.22 Preoperative administration of amiodarone and sotalol may reduce the incidence of atrial fibrillation in patients undergoing cardiac surgery. As such, these agents may be used as prophylactic therapy in those at high risk for postoperative atrial fibrillation.
Retrospective data suggest that atrial-based pacing (AAI, DDD modes) reduces the risk of developing atrial fibrillation and increases the interval between episodes in patients with sick sinus syndrome.23
Surgical Care
Since its inception, surgical compartmentalization of the atria, or the MAZE procedure, has evolved as an exciting procedure with a potential to cure atrial fibrillation. Quite simply, the atria are transected and resutured to reduce the critical mass required for the maintenance of atrial fibrillation. Early experience shows that atrial transport is restored postoperatively and that long-term anticoagulation is not required. The downside remains the need for an open chest procedure; however, thoracoscopic procedures may reduce hospitalization and recovery times in the future. The surgical MAZE procedure remains an attractive procedure for patients with atrial fibrillation who are undergoing concomitant mitral valve procedures. Its role as a primary therapy for atrial fibrillation is doubtful.
Catheter ablation has taken the following 3 paths in the attempt to cure or manage atrial fibrillation.
- Compartmentalization of the atria with continuous ablation lines of block
- Parallel to the surgical MAZE procedure, electrophysiologists are attempting to recreate surgical suture lines with radiofrequency lesions.
- The procedures tend to last many hours, and the success rates are somewhat disappointing (50-60%), with left atrial reentrant tachycardias and left atrial flutters appearing (requiring further ablation procedures).24
- Researchers are unsure which areas of the atria are necessary to sustain atrial fibrillation. Purely right-sided lesions are not sufficient to eliminate atrial fibrillation, making left atrial procedures necessary. In addition, gaps in linear lesions can be difficult to find.
- Research currently focuses on catheter design to deliver linear continuous lesions. Additionally, alternative energy sources (ie, cooling, LASER, ultrasonography) may improve one's ability to deliver transmural lesions in the left atrium.
- Catheter ablation of focal triggers of atrial fibrillation
- In some patients, atrial fibrillation seems to be triggered by electrically active pulmonary vein foci. These foci can trigger the atria to fibrillate.25
- Patients typically have an abundance of ectopic atrial beats noted on 24-hour Holter monitoring. Electrical isolation of individual pulmonary veins, and thus the ectopic foci, is performed successfully at many centers, and patient selection is key to success. A combined procedure including individual pulmonary vein isolation, as well as left atrial ablation (ie, encircling pulmonary vein pairs, connecting right and left pairs along the left atrial roof, and connection to the mitral valve annulus) is often necessary. The use of chest CT or MRI can be used to recreate 3-dimensional anatomy in the left atrium, thus aiding in mapping and creating contiguous lines in the left atrium. In addition, multiple procedures are often necessary.
- Complications are generally in the 5% range and include pulmonary vein stenosis (that can be symptomatic), perforation, thromboembolism, and tamponade. Still, cure rates as high as 70-80% have been reported in properly selected patients (patients with frequent atrial premature beats and episodes of paroxysmal atrial fibrillation).
- Atrioventricular node ablation and insertion of a permanent pacemaker
- AV node ablation may represent an alternative in patients with chronic atrial fibrillation and an uncontrolled ventricular response despite aggressive medical therapy.
- Catheter ablation of the AV junction permanently interrupts conduction from the atria to the ventricles.
- Because the result is permanent AV block, a permanent pacemaker is required. atrial fibrillation may still exist, but the pacemaker governs the ventricular response.
- The risk of thromboembolism is unchanged, and patients still require anticoagulation; however, most patients are relieved of their symptoms.
- During the first 1-3 months, the pacing rate must be programmed in the 80- to 90-beat range to prevent TdP, which has been reported in the literature, presumably due to slow ventricular rates and the occurrence of early after-depolarizations.
- In patients with significant ventricular dysfunction and permanent ventricular pacing, a biventricular device may be appropriate.26
- Improvements in LV size and function, functional class, and quality-of-life scores have been demonstrated.27
- Percutaneous closure of the left atrial appendage.
- Embolic stroke in patients with nonvalvular atrial fibrillation (AF) is thought to be associated with left atrial appendage (LAA) thrombi. Holmes and colleagues compared the efficacy and safety of percutaneous closure of the left atrial appendage versus warfarin therapy in patients with atrial fibrillation.28 Eligible patients (n=707) were randomly assigned in a 2:1 ratio to LAA percutaneous closure and discontinuation of current warfarin (intervention; n=463) or to warfarin treatment (control; n=244). Follow-up at the point of 1065 patient-years showed the intervention group event rate was 3 per 100 patient-years compared with the control group of 4.9 per 100 patient-years. Probability of noninferiority of the intervention was greater than 99.9%. Although a higher rate for adverse safety events was observed in the intervention group, LAA may be a suitable alternative to chronic warfarin therapy for stroke prophylaxis in patients with nonvalvular atrial fibrillation.
Consultations
Consultation with a cardiac electrophysiologist or knowledgeable clinician is recommended prior to antiarrhythmic drug initiation.
Diet
Diet restrictions, if any, are as appropriate for the underlying heart disease and any other comorbidities (eg, diabetes mellitus).
Medication
The goals of medical therapy for patients with atrial fibrillation 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. The ACTIVE trial studied 7554 patients with atrial fibrillation with the intent to determine if adding clopidogrel to aspirin therapy would reduce the risk for acute vascular events (ie, stroke, myocardial infarction, non-CNS systemic embolism, or death from vascular event) in patients unable to take warfarin. Addition of clopidogrel to aspirin reduced the risk of major vascular events (P=0.01), especially stroke (P=0.001), compared with placebo and aspirin. Increased risk for major hemorrhage was more prevalent in the clopidogrel plus aspirin group than the placebo and aspirin group.30
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. Currently, the FDA has approved 5 antiarrhythmic drugs (quinidine, flecainide, propafenone, sotalol, dofetilide) for the treatment of atrial fibrillation. Other antiarrhythmic agents (eg, 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 pre-existing arrhythmias and generate arrhythmia de novo. Tachy- and brady-arrhythmias generated by these agents can be of ventricular or atrial origin. Drug-drug interactions and extra-cardiac 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 ACA/AHA/ECC have jointly developed guidelines for the long-term antiarrhythmic treatment in the maintenance of sinus rhythm.3 The following algorithm incorporates clinical trial data on the safety and efficacy of antiarrhythmic agents. These guidelines are intended to help clinicians tailor antiarrhythmic therapy on an individual basis for their patients.
For patients with no evidence of structural heart disease, flecainide, propafenone and sotalol should be considered first-line agents. Amiodarone or dofetilide can be considered as alternative agents. For patients with substantial left ventricular hypertrophy (LVH), amiodarone is considered a reasonable first-line agent. For patients with coronary artery disease, dofetilide or sotalol are first-line therapy. Amiodarone is considered a second-line agent in this population. For patients with heart failure, amiodarone or dofetilide are first-line agents. See Media file 4.
Antiarrhythmic drug algorithm for the medical management of sinus rhythm in patients with atrial fibrillation.
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. While the proarrhythmic effect of these drugs extends into the maintenance phase, inpatient drug initiation is generally recommended in the monitored inpatient setting, 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.
Atrioventricular nodal conduction blockers
Used to slow ventricular response by slowing AV nodal conduction during atrial fibrillation or atrial flutter. Also indicated for use in conjunction with class IA and IC antiarrhythmics, which slow atrial fibrillation/flutter rate and may cause more rapid ventricular response.
Esmolol (Brevibloc)
Ultra–short-acting. Selectively blocks beta1-receptors with little or no effect on beta2-receptor types. Particularly useful in patients with elevated arterial pressure, especially if surgery is planned. Shown to reduce episodes of chest pain and clinical cardiac events compared with placebo. Can be discontinued abruptly if necessary. Useful in patients at risk for experiencing complications from beta-blockade, particularly those with reactive airway disease, mild-moderate LV dysfunction, and/or peripheral vascular disease. Short half-life of 8 min allows for titration to desired effect and quick discontinuation if needed.
Adult
250-500 mcg/kg/min for 1 min loading dose followed by a 4 min maintenance infusion of 50 mcg/kg/min
If adequate therapeutic effect not observed within 5 min, repeat loading dose and follow with maintenance infusion using increments of 50 mcg/kg/min (for 4 min); sequence may be repeated up to 4 times prn
As the desired heart rate approached, omit loading infusion and reduce incremental dose of maintenance infusion from 50 mcg/kg/min to 25 mcg/kg/min or lower; interval between titration steps may be increased from 5 min to 10 min if needed
Pediatric
Not established; 100-500 mcg/kg administered over 1 min suggested
Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels of esmolol, possibly resulting in decreased pharmacologic effect; cardiotoxicity of esmolol may increase when administered concurrently with sparfloxacin, astemizole, calcium channel blockers, quinidine, flecainide, and contraceptives; toxicity of esmolol increases when administered concurrently with digoxin, flecainide, acetaminophen, clonidine, epinephrine, nifedipine, prazosin, haloperidol, phenothiazines, and catecholamine-depleting agents
Documented hypersensitivity; uncompensated congestive heart failure, bradycardia, cardiogenic shock, and A-V conduction abnormalities
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Beta-adrenergic blockers may mask signs and symptoms of acute hypoglycemia and clinical signs of hyperthyroidism; symptoms of hyperthyroidism, including thyroid storm may worsen when medication is abruptly withdrawn; withdraw drug slowly and monitor patient closely
Propranolol (Inderal)
Class II antiarrhythmic, nonselective, beta-adrenergic receptor blocker with membrane-stabilizing activity that decreases automaticity of contractions.
Adult
1-3 mg (under careful monitoring) IV; not to exceed 1 mg/min IV to avoid lowering blood pressure and causing cardiac standstill
Allow time for drug to reach site of action (particularly if slow circulation); administer second dose after 2 min prn; thereafter, do not administer additional drug after desired alteration in rate or rhythm achieved; switch to 10-160 mg PO bid
Pediatric
2-4 mg/kg/d PO divided bid (1-2 mg/kg bid)
IV use not recommended; however, for arrhythmias, 0.01-0.1 mg/kg, not to exceed 1 mg/dose, by slow push has been recommended; change to PO as soon as possible
Coadministration with aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease effects; calcium channel blockers, cimetidine, loop diuretics, and MAOIs may increase toxicity; toxicity of hydralazine, haloperidol, benzodiazepines, and phenothiazines may increase
Documented hypersensitivity; uncompensated CHF; bradycardia, cardiogenic shock; AV conduction abnormalities, reactive airway disease
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Beta-adrenergic blockade may decrease signs of acute hypoglycemia and hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; withdraw drug slowly and monitor patient closely
Atenolol (Tenormin)
Selectively blocks beta-1 receptors with little or no effect on beta-2 types. Esmolol 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. Short half-life of 8 min allows for titration to desired effect and quick discontinuation if needed.
Adult
Up to 200 mg PO qd
Pediatric
Not established
Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly resulting in decreased pharmacologic effect; cardiotoxicity may increase when administered concurrently with sparfloxacin, astemizole (recalled from US market), calcium channel blockers, quinidine, flecainide, and contraceptives; toxicity increases when administered concurrently with digoxin, flecainide, acetaminophen, clonidine, epinephrine, nifedipine, prazosin, haloperidol, phenothiazines, and catecholamine-depleting agents
Documented hypersensitivity, CHF, pulmonary edema, cardiogenic shock, AV conduction abnormalities, heart block (without a pacemaker), reactive airway disease
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Beta-adrenergic blockade may reduce symptoms of acute hypoglycemia and mask signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism and cause thyroid storm; monitor patients closely and withdraw drug slowly; during IV, carefully monitor BP, heart rate, and ECG
Metoprolol (Lopressor)
Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. During IV administration, carefully monitor blood pressure, heart rate, and ECG.
Adult
5 mg IV for 3 doses q2-5 min; then up to 200 mg PO bid
Pediatric
Not established
Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly resulting in decreased pharmacologic effects; toxicity may increase with coadministration of sparfloxacin, phenothiazines, astemizole (recalled from US market), calcium channel blockers, quinidine, flecainide, and contraceptives; may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine
Documented hypersensitivity, uncompensated CHF, bradycardia, asthma, cardiogenic shock, and AV conduction abnormalities, reactive airway disease
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Beta-adrenergic blockade may reduce signs and symptoms of acute hypoglycemia and may decrease clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; monitor patient closely and withdraw drug slowly; during IV administration, carefully monitor blood pressure, heart rate, and ECG
Digoxin (Lanoxin)
Slows sinus node and AV node via vagomimetic effect and not very effective if sympathetic tone is increased. Generally not recommended unless depressed LV function is present.
Adult
Loading dose: 1.5-2 mg PO/IV in divided dose over 1-2 d
Maintenance dose: 0.25 mg PO/IV qd
Pediatric
Premature neonates: 15-25 mcg/kg PO/IV divided into 3 or more doses (first dose equalling half total dose), then remaining doses q6-8h; maintenance of 4-6 mcg/kg/d PO/IV divided bid
Neonates: 20-30 mcg/kg PO/IV divided into 3 or more doses (first dose equalling half total dose), then remaining doses q6-8h; maintenance of 5-8 mcg/kg/d PO/IV divided bid
<2 years: 30-50 mcg/kg PO/IV divided into 3 or more doses (first dose half total dose), then remaining doses q6-8h; maintenance of 7.5-12 mcg/kg/d PO/IV divided bid
2-5 years: 25-35 mcg/kg PO/IV divided into 3 or more doses (first dose equalling half total dose), then remaining doses q6-8h; maintenance of 6-9 mcg/kg/d PO/IV divided bid
6-10 years: 15-30 mcg/kg PO/IV divided into 3 or more doses (first dose equalling half total dose), then remaining doses q6-8h; maintenance of 4-8 mcg/kg/d PO/IV divided bid
>10 years: 8-12 mcg/kg PO/IV divided into 3 or more doses, (first dose equalling half total dose), then remaining doses q6-8h; maintenance of 2-3 mcg/kg/d PO/IV qd
Medications that may increase levels include alprazolam, benzodiazepines, bepridil, captopril, cyclosporine, propafenone, propantheline, quinidine, diltiazem, aminoglycosides, oral amiodarone, anticholinergics, diphenoxylate, erythromycin, felodipine, flecainide, hydroxychloroquine, itraconazole, nifedipine, omeprazole, quinine, ibuprofen, indomethacin, esmolol, tetracycline, tolbutamide, and verapamil
Medications that may decrease serum levels include aminoglutethimide, antihistamines, cholestyramine, neomycin, penicillamine, aminoglycosides, oral colestipol, hydantoins, hypoglycemic agents, antineoplastic treatment combinations (including carmustine, bleomycin, methotrexate, cytarabine, doxorubicin, cyclophosphamide, vincristine, and procarbazine), aluminum or magnesium antacids, rifampin, sucralfate, sulfasalazine, barbiturates, kaolin/pectin, and aminosalicylic acid
Documented hypersensitivity, beriberi heart disease, idiopathic hypertrophic subaortic stenosis, constrictive pericarditis, carotid sinus syndrome
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hypokalemia may reduce positive inotropic effect of digitalis; IV calcium may produce arrhythmias in digitalized patients; hypercalcemia predisposes patient to digitalis toxicity; hypocalcemia can make digoxin ineffective until serum calcium levels are normal; institute magnesium replacement therapy in patients with hypomagnesemia to prevent digitalis toxicity; patients diagnosed with incomplete AV block may progress to complete block when treated with digoxin; exercise caution in hypothyroidism, hypoxia, and acute myocarditis
Antiarrhythmics, class IA
Quinidine, procainamide, and disopyramide are IA antiarrhythmic agents used to maintain sinus rhythm. Generally, start administration in hospital because of 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 atrial rate and an increase in AV conduction with rapid ventricular rates when treated with IA agents alone. Fading as first-line drugs for atrial fibrillation.
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 main ECG manifestations. Should not be used in patients with a prolonged QTc baseline (>460 milliseconds). Generally has fallen out of favor as a first- or second-line agent for treatment of atrial fibrillation.
Adult
300 mg PO q8-12h
324 mg PO q8h of quinidine gluconate formulation
Pediatric
Not established
Slows elimination of digoxin and simultaneously reduces volume of distribution, leading to increased serum digoxin level; potentiates anticoagulant effect of warfarin
Prior thrombocytopenic purpura during quinidine administration; complete heart block, unless a ventricular pacemaker is present, long QTc at baseline (>460 milliseconds), history of TdP
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Renal or hepatic dysfunction causes reduction in elimination half-life of parent drug and/or metabolites; CHF causes a reduction in apparent volume of distribution; any of these conditions can result in quinidine toxicity if dosage not appropriately reduced; perform periodic blood counts and liver and kidney tests during long-term therapy; in general, initiate during continuous cardiac monitoring, with careful attention to the QTc interval
Procainamide (Procanbid, Pronestyl)
Not FDA-approved for treatment of atrial fibrillation; however, many use this agent for acute cardioversion (eg, postoperatively) and because it can be administered IV. Administered IV, useful for acute conversion and can subsequently be converted to oral dose. Negative inotropic agent and vasodilator, and care must be taken in administering to patients with reduced LV function. Generally considered second-line agent.
Adult
1000-2500 mg PO q12h (Procanbid formulation) based on body weight and normal renal function; not to exceed 18 mg/kg over 1 h with initial infusion
Procainamide and N -acetyl procainamide (NAPA) levels should be drawn after steady state reached
Pediatric
Not established
Can expect increased levels of procainamide metabolite NAPA (a class III antiarrhythmic agent) in patients taking cimetidine, ranitidine, beta-blockers, amiodarone, trimethoprim, and quinidine; may increase effect of skeletal muscle relaxants (eg, quinidine, lidocaine) and neuromuscular blockers; ofloxacin inhibits tubular secretion of procainamide and may increase bioavailability; when taken concurrently with sparfloxacin, may increase risk of cardiotoxicity
History of complete heart block, unless a ventricular pacemaker present; lupus erythematosus; TdP; long QTc at baseline (>460 milliseconds)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Agranulocytosis rate of 0.5% with 20-25% mortality; weekly CBC counts recommended for first 3 mo and regularly thereafter
Renal clearance; renal insufficiency may lead to accumulations of high plasma levels and its active metabolite, NAPA
In general, initiate during continuous cardiac monitoring, with careful attention to QTc interval
Disopyramide (Norpace)
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. May be useful in vagally mediated syncope.
Adult
150 mg PO q6h
300 mg PO q12h (CR formulation)
Pediatric
<12 years: 6-20 mg/kg/d PO divided q6h
>12 years: Administer as in adults
Phenytoin, rifampin, and phenobarbital may decrease effects; toxicity increases with erythromycin and sparfloxacin; levels of digoxin increase
Documented hypersensitivity; history of complete heart block; sick sinus syndrome, cardiogenic shock; CHF; prolonged baseline QTc (>460 milliseconds)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Dose adjustments necessary in liver disease, renal disease, and elderly persons; anticholinergic effects can cause urinary retention and blurred vision
In general, initiate during continuous cardiac monitoring, with careful attention to QTc interval
Antiarrhythmics, class IC
Indicated for patients with atrial fibrillation and supraventricular tachycardia without structural heart disease. Given the results of the CAST I and II trials (increased mortality), type IC agents are generally not used in patients with concomitant LV dysfunction and/or CAD. Applicability of 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 atrial fibrillation 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)
Shortens upstroke velocity (phase 0) of monophasic action potential. Reduces fast inward current carried by sodium ions in Purkinje fibers and, to a lesser extent, myocardial fibers. May increase diastolic excitability threshold and prolong effective refractory period. Reduces spontaneous automaticity and depresses triggered activity.
Indicated for documented life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia. Appears to be effective in treatment of supraventricular tachycardias, including atrial fibrillation and flutter. Not recommended in patients with less severe ventricular arrhythmias, even if symptomatic. Use 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) has been noted.
Adult
150-300 mg PO tid
225, 325, 425 mg PO bid (SR formulation)
Pediatric
Not established
Rifampin may decrease plasma levels; quinidine may increase pharmacologic effects; may increase plasma levels of beta-blockers, cyclosporine, warfarin, and digoxin; CYP4502D6 inhibitors (ritonavir, cimetidine, amiodarone) may increase serum levels and cardiotoxicity
Documented hypersensitivity, second- or third-degree AV block, right bundle-branch block associated with left hemiblock (bifascicular block) or trifascicular block; concurrent use of ritonavir or amprenavir
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in preexisting sinus node dysfunction, history of CHF, post MI, myocardial dysfunction, or sick sinus syndrome (exacerbates sick sinus syndrome and causes sinus pauses or sinus arrest); reserve use for life-threatening arrhythmias only due to deaths associated with proarrhythmic effects of class IC antiarrhythmics; highly metabolized in liver; considerable percentage of metabolites (18-35%) excreted in urine; patients with impaired liver and renal function need careful monitoring for excessive pharmacological effects (adjust dose); rarely, positive ANA titers are reported, are reversible upon cessation of treatment, and may even disappear with continued therapy
Flecainide (Tambocor)
Blocks sodium and potassium channels, producing dose-related decrease in intracardiac conduction in all parts of heart. Increases electrical stimulation of threshold of ventricle, His-Purkinje system. Shortens phase 2 and 3 repolarization, resulting in decreased action potential duration and effective refractory period.
Indicated for 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. Also indicated for prevention of documented life-threatening ventricular arrhythmias (eg, sustained ventricular tachycardia). Not recommended in less severe ventricular arrhythmias even if patients are symptomatic. Use 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.
Adult
50-150 mg PO bid
Pediatric
Not established
May increase toxicity of digoxin; beta-adrenergic blockers, verapamil, and disopyramide may have additive inotropic effects when coadministered; CYP4502D6 inhibitors (ritonavir, cimetidine, amiodarone) may increase serum levels and cardiotoxicity
Documented hypersensitivity, preexisting second- or third-degree AV block, right bundle-branch block associated with left hemiblock (bifascicular block) or trifascicular block), unless a pacemaker is present to sustain cardiac rhythm if complete heart block occurs; concurrent use of ritonavir or amprenavir; recent MI
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in preexisting sinus node dysfunction, history of CHF, post MI, myocardial dysfunction, or sick sinus syndrome (exacerbates sick sinus syndrome and causes sinus pauses or sinus arrest); reserve use for life-threatening arrhythmias only due to deaths associated with proarrhythmic effects of class IC antiarrhythmics; adjust dose in renal or hepatic impairment; known to increase endocardial pacing thresholds; may suppress ventricular escape rhythms
Antiarrhythmics, class III
Currently, class III antiarrhythmic agents sotalol and dofetilide are FDA-approved for use in treating atrial arrhythmias; however, amiodarone is also widely used in maintenance of sinus rhythm in patients with atrial fibrillation. Dofetilide must be initiated in an inpatient setting. Sotalol is also initiated in an inpatient setting.
Amiodarone (Cordarone)
Has antiarrhythmic effects that overlap all 4 Vaughn-Williams antiarrhythmic classes. Has a low risk of proarrhythmia, and any proarrhythmic reactions generally are delayed. 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 goal of lowest dose with desired therapeutic benefit (usual maintenance dose for atrial fibrillation is 200 mg/d). During loading, patients must be monitored for bradyarrhythmias.
Adult
400 mg PO tid for 1 wk, followed by weekly reductions (goal of lowest dose with desired therapeutic benefit)
Maintenance for atrial fibrillation: 200 mg/d
Pediatric
Not established
Increases effect and blood levels of theophylline, methotrexate, digoxin, cyclosporine, beta-blockers, and anticoagulants; cardiotoxicity is increased by ritonavir and sparfloxacin; coadministration with calcium channel blockers may cause an additive effect and may further decrease myocardial contractility; cimetidine may increase levels
Documented hypersensitivity, complete AV block and intraventricular conduction defects; patients taking ritonavir or sparfloxacin
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Pulmonary toxicity has a 3-7% incidence and is dose-related, rare with doses <400 mg/d; gallium scan and lung biopsies confirm diagnosis; discontinuation with administration of steroids is preferred; assess baseline thyroid, liver, and pulmonary functions; perform thyroid and liver studies at regular intervals (6 mo); perform yearly chest radiographs, looking for evidence of pulmonary fibrosis; toxicity and adverse effects are a function of daily dose and duration of therapy, making this drug less desirable in younger populations; use with extreme caution in patients with severe pulmonary disease (can cause pulmonary fibrosis and death); regular ophthalmologist examinations due to rare cases of optic neuritis
Sotalol (Betapace atrial fibrillation)
Class III agent with beta-blocking effects. Effective in maintenance of sinus rhythm, even in patients with underlying structural heart disease. Inpatient loading is FDA-mandated.
Adult
80 mg PO bid initially, with therapeutic goal of 120-160 mg PO bid
Pediatric
Not established
Class IA antiarrhythmic agents, disopyramide, quinidine, procainamide; other class III agents (amiodarone) can enhance potassium channel blocking effect and should not be given concomitantly
Prolonged QTc at baseline (generally >500 milliseconds); history of TdP; reactive airway disease; renal failure; electrolyte abnormalities
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Risk factors for sotalol-induced TdP (1.5-2%) include impaired renal function (creatinine >1.4), hypokalemia, female sex, slow heart rates, daily dose >320 mg, history of CHF or VT/VF, and QTc >500-525 milliseconds
Dofetilide (Tikosyn)
Approved by FDA for maintenance of sinus rhythm as well as for the conversion of atrial fibrillation to sinus rhythm (approx 50%) in patients with persistent atrial fibrillation. 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. No evidence of negative inotropic effect.
Adult
125, 250, or 500 mcg PO bid; must be started in a monitored inpatient setting for 3 days by certified clinician
Dose determined by creatinine clearance (CrCl) and QTc response to initial doses
Pediatric
Not established
Verapamil, TMP-SMZ, ketoconazole, potassium-depleting diuretics, digoxin, cimetidine, phenothiazines, triamterene, metformin, prochlorperazine, amiloride, megestrol, and other antiarrhythmic agents may increase toxicity
Documented hypersensitivity; CrCl <20 mL/min; QTc >440 milliseconds at baseline and >500 milliseconds after second dose; do not use in conjunction with trimethoprim (either alone or in combination with sulfamethoxazole), verapamil, ketoconazole, cimetidine, megestrol, phenothiazines, TCAs, or prochlorperazine
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Tightly regulated and can be prescribed only by clinicians who register with company and have specific training; to minimize risk of induced arrhythmia, calculations of CrCl and continuous ECG monitoring must be performed; cardiac resuscitation equipment and personnel must be present; maintain potassium levels within reference range prior to and during administration
Ibutilide (Corvert)
Indicated for conversion of recent-onset atrial fibrillation or atrial flutter (3 h to 90 d). Prolongs repolarization by increasing slow inward sodium current and by blocking delayed rectifier current with rapid onset.
Adult
>60 kg (132 lb): 1 mg IV infusion over 10 min
<60 kg: 0.01 mg/kg IV over 10 min; second infusion of equal strength can be given 10 min after first prn
Magnesium infusion (2 g MgSO4) has been used to pretreat patients receiving ibutilide to prevent TdP
Pediatric
Not established
Increases toxicity of quinidine and procainamide; concurrent administration with TCAs, phenothiazines, and astemizole (recalled from US market) may prolong QT interval; toxicity of digoxin increases when administered concurrently
Documented hypersensitivity; history of TdP; concurrent use of other QT prolonging agents
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Of 586 patients with recent-onset atrial fibrillation or AFL who received ibutilide, 149 reported medical events related to cardiovascular system, including sustained polymorphic VT (1.7%) and nonsustained polymorphic VT (2.7%); observe patients with continuous ECG monitoring for at least 4 h following infusion or until QTc returns to baseline; skilled personnel and proper equipment (defibrillator and medication for treatment of life-threatening ventricular arrhythmias) must be available during monitoring period
Patients should not be given class IA agents (quinidine, disopyramide, procainamide) or class III drugs (sotalol, amiodarone) concomitantly with or within 4 h postinfusion because of their potential to prolong refractoriness; potential for proarrhythmia exists with other drugs that prolong the QT interval (eg, phenothiazines, TCAs, certain antihistamines); risk of TdP higher if ventricular rate or severely reduced LV function
Antiarrhythmic Agent, Miscellaneous
Dronedarone is an antiarrhythmic agent with properties belonging to all 4 Vaughn-Williams antiarrhythmic classes.
Dronedarone (Multaq)
Blocks sodium channels, blocks beta1-adrenergic site, and alters adenyl cyclase generation (ie, negative inotropic effects); blocks potassium channels (eg, hERG) and therefore prolongs cardiac repolarization.
In a multinational clinical trial (n >4600), dronedarone reduced cardiovascular hospitalization or death from any cause by 24% compared with placebo.
Indicated to reduce risk for cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF) or atrial flutter (AFL), with a recent episode of AF/AFL 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.
Adult
400 mg PO bid with meals
Pediatric
Not established
CYP3A4 substrate, moderate CYP3A4 and CYP2D6 inhibitor; P-gP inhibitor
Avoid coadministration with CYP3A4 inhibitors (eg, itraconazole, azithromycin, erythromycin, grapefruit juice) that may decrease clearance and thereby increase dronedarone plasma levels (see Contraindications); avoid use with CYP3A4 inducers (eg, rifampin, carbamazepine) because of increased clearance and consequent reduction in dronedarone serum levels; use with other drugs that prolong QT interval (eg, phenothiazine, TCAs, macrolide antibiotics, class I and III antiarrhythmic agents) may cause life-threatening arrhythmias (see Contraindications)
When coadministered with P-gP substrates (eg, digoxin), P-gP substrate bioavailability may increase (consider discontinuing P-gp substrate or decrease P-gP substrate dose by 50%)
Coadministration increases serum levels of HMG-CoA reductase inhibitors (eg, atorvastatin), thereby increasing risk for adverse effects (eg, myopathy); monitor serum levels of CYP3A substrates with narrow therapeutic indexes (eg, sirolimus, tacrolimus) if coadministered
Coadministration with beta-blockers or calcium channel blockers requires lowered dose of these agents and dose should only be increased after ECG verification of tolerability
Documented hypersensitivity; severe heart failure (ie, NYHA class IV) or NYHA class II-III with recent decompensation requiring hospitalization or referral to heart failure program; second- or third-degree heart block or sick sinus syndrome (unless functioning pacemaker in place); bradycardia <50 bpm; QTc interval >500 milliseconds (coadministration with other drugs that prolong QT interval may cause torsade de pointes[en dash]type ventricular tachycardia); severe hepatic impairment; strong CYP3A4 inhibitors
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Boxed warning: May cause critical adverse reactions, including death, in patients with recent severe heart failure
Common adverse reactions include diarrhea, nausea, vomiting, fatigue, and asthenia; discontinue if new or worsening heart failure develops; monitor QT interval; hypomagnesemia and hypokalemia may increase risk for serious arrhythmic event
Anticoagulants
Used to prevent thromboembolic complications.
Heparin
Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis. Most data related to use of unfractionated heparin. Low–molecular-weight heparin can also be utilized
Adult
60 U/kg IV initially, followed by maintenance infusion of 12 U/kg/h IV; target aPTT is 50-70 seconds
Pediatric
50 U/kg IV initially, followed by a maintenance infusion of 15-25 U/kg/h IV; increase dose by 2-4 U/kg/h q6-8h prn, using aPTT results
Digoxin, nicotine, tetracycline, and antihistamines may decrease effects; NSAIDs, ASA, dextran, dipyridamole, and hydroxychloroquine may increase toxicity
Documented hypersensitivity, subacute bacterial endocarditis, active bleeding, history of heparin-induced thrombocytopenia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Bleeding; in neonates, preservative-free heparin is recommended to avoid possible toxicity (gasping syndrome) by benzyl alcohol, which is used as preservative; caution in severe hypotension and shock
Enoxaparin Sodium (Lovenox)
Low molecular weight heparin. Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis.
Adult
1 mg/kg given as a sub cuticular injection bid assuming normal renal function;
kinetics in patients more than 100 kg not well studied
Pediatric
May be used for thromboembolic disorders
In a pilot study, 23 consecutive pediatric patients at an increased risk of bleeding with heparin were treated with subcutaneous enoxaparin 1 mg/kg q12h with subsequent doses adjusted to achieve a 4-hour anti-factor Xa level between 0.5-1 unit/mL for various thrombotic diseases. Six of the 7 infants (<2 mo) required (based on anti-factor Xa levels) an average dose of 1.64 mg/kg bid. 3 children required a dose reduction to 0.5 mg/kg bid. Duration of treatment ranged from 10 days or less to more than 60 days. Thrombotic events were deep vein thrombosis, pulmonary embolism, and thrombotic complication in the CNS. No new thrombotic events occurred and 2 patients, with previous diagnosed gastrointestinal ulcers, experienced bleeding that required transfusion
Digoxin, nicotine, tetracycline, and antihistamines may decrease effects; NSAIDs, aspirin, dextran, dipyridamole, and hydroxychloroquine may increase toxicity
Active major bleeding, hypersensitivity to enoxaparin, heparin, pork products, benzyl alcohol (multi-dose formulation), thrombocytopenia associated with a positive test for antiplatelet antibody in the presence of enoxaparin; significant renal dysfunction
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Bacterial endocarditis; increased risk of hemorrhage; bleeding diathesis; concomitant platelet inhibitors; increased risk of hemorrhage; congenital or acquired bleeding disorders; increased risk of hemorrhage; diabetic retinopathy; elderly patients; potential for delayed elimination of enoxaparin;
gastrointestinal disease, ulcerative and angiodysplastic, active or recent; increased risk of hemorrhage; hemorrhagic stroke; increased risk of hemorrhage, heparin-induced thrombocytopenia, history of; use extreme caution; low-weight men (<57 kg) and women (<45 kg); increased exposure to enoxaparin and increased risk for bleeding; major hemorrhage (including intracranial and retroperitoneal) or bleeding at any site may occur; investigate any unexplained reduction in hematocrit or blood pressure; recent brain, spinal, or ophthalmologic surgery (increased risk of hemorrhage); renal impairment; increased exposure to enoxaparin and increased risk for bleeding, dosage adjustment recommended in patients with CrCl <30 mL/min; thrombocytopenia may occur, discontinue therapy if platelet count falls below 100,000/mm; uncontrolled hypertension
Warfarin (Coumadin)
Interferes with hepatic synthesis of vitamin K–dependent coagulation factors. Used for prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders. Tailor dose to maintain INR of 2-3.
Adult
1-20 mg/d PO qd, adjust dose to desired INR (2-3) for nonvalvular atrial fibrillation/flutter
Pediatric
0.05-0.34 mg/kg/d PO; adjust dose according to weight and desired INR
Drugs that may decrease anticoagulant effects include griseofulvin, carbamazepine, glutethimide, estrogens, nafcillin, phenytoin, rifampin, barbiturates, cholestyramine, colestipol, vitamin K, spironolactone, oral contraceptives, and sucralfate
Medications that may increase anticoagulant effects include oral antibiotics, phenylbutazone, salicylates, sulfonamides, chloral hydrate, clofibrate, diazoxide, anabolic steroids, ketoconazole, ethacrynic acid, miconazole, nalidixic acid, sulfonylureas, allopurinol, chloramphenicol, cimetidine, disulfiram, metronidazole, phenylbutazone, phenytoin, propoxyphene, sulfonamides, gemfibrozil, acetaminophen, and sulindac
Documented hypersensitivity; severe liver or kidney disease; open wounds or GI ulcers; pregnancy, although AHA/ACC guidelines for pregnant patients with mechanical valves mention that risk of thrombotic mechanical valve may be higher than risk of teratogenicity from warfarin
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Do not switch brands after achieving therapeutic response; caution in active tuberculosis or diabetes; patients with protein C or S deficiency are at risk of developing skin necrosis
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Further Reading
Keywords
atrial fibrillation, a fib, atrial fib, arrhythmia, AFL, supraventricular tachycardia, SVT, congestive heart failure, CHF, ventricular tachycardia, VT, ventricular fibrillation, VF, coronary artery disease, CAD, thromboembolic stroke, uncontrolled hypertension, coronary disease, valvular heart disease, acute pulmonary processes, acute pulmonary disease, hyperthyroidism, acute alcohol intoxication, holiday heart, Saturday night heart, illicit narcotic abuse, drug abuse, tachycardia-induced cardiomyopathy, rheumatic heart disease, rheumatic valvular disease, hypertension, diabetes, thromboembolism, recurrent atrial fibrillation, paroxysmal atrial fibrillation, permanent atrial fibrillation, chronic atrial fibrillation
thyrotoxicosis, electrolyte abnormalities, acute ethanol intoxication, atrial premature beats, Holter monitoring, hypertensive heart disease, dilated cardiomyopathy, atrial cardiomyopathy, Maze procedure, electrical cardioversion, ischemic stroke, Wolff-Parkinson-White syndrome, hepatojugular reflex, atrial flutter
