Research ArticlePractice

Rate versus rhythm control in atrial fibrillation

Grace Frankel, Rejina Kamrul, Lynette Kosar and Brent Jensen
Canadian Family Physician February 2013; 59 (2) 161-168;

Article Figures & Data

Figures

Tables

  • Table 1 Identification of type of AF
    TYPE OF AFDEFINITION
    ParoxysmalTerminates spontaneously within 7 d
    PersistentLasts longer than 7 d or is terminated pharmacologically or electrically
    PermanentDoes not terminate, even with cardioversion attempts

    • AF–atrial fibrillation.

    • Data from Gillis et al1 and Sanoski and Bauman.3

  • Table 2 Underlying causes of AF
    CARDIOVASCULAR CAUSESNONCARDIOVASCULAR CAUSES
    HypertensionHyperthyroidism*
    Valvular heart diseaseAutonomically mediated (vagal) causes
    Coronary artery diseaseAlcoholism (“holiday heart”)* or alcohol withdrawal
    Heart failure* or cardiomyopathyObstructive sleep apnea* or obesity*
    Genetic or familial causesPharmacologic agents (stimulants, digoxin toxicity, illicit drugs)
    Post cardiac surgeryNeurologic insult
    Congenital heart disease*Excessive physical exertion*
    Sick sinus syndromeSepsis
    Pacemaker*Pulmonary disease (chronic obstructive pulmonary disease)

    • AF–atrial fibrillation.

    • ↵* Management of these risk factors prevents development or recurrence of AF.

    • Data from Gillis et al,1 Sanoski and Bauman,3 and Jin and Kosar.4

  • Table 3 Factors favouring rate versus rhythm control
    FAVOURING RATE CONTROLFAVOURING RHYTHM CONTROL
    Persistent AFParoxysmal AF or newly detected AF
    Less symptomaticMore symptomatic
    Age ≥ 65 yAge < 65 y
    HypertensionNo hypertension
    No history of HFHF clearly exacerbated by AF
    Previous failure of antiarrhythmic drugNo previous failure of antiarrhythmic drug
    Patient preferencePatient preference

    • AF–atrial fibrillation, HF–heart failure.

    • Data from Gillis et al.1

  • Table 4 Rate versus rhythm control meta-analyses summary
    META-ANALYSISSTUDIES INCLUDEDPATIENTSKEY FINDINGS
    Caldeira et al,5 20128 RCTs (PIAF,9 RACE,10 AFFIRM,11 STAF,12 HOT CAFE,13 AF-CHF,14 J-RHYTHM,15 CAFE-II16)N = 7499 participants with AF, mean age 68 y, mostly men (63.4%-82%); HTN (42.8%-64.3%), valvular disease (4.9%-17%), CAD (7.4%-43.5%), HF (3.6%-70%); mean follow-up 2.9 y (range 1-3.5 y)No significant difference between rate and rhythm control in all-cause mortality, CV mortality, arrhythmia or sudden death, ischemic stroke or embolic events, or serious bleeding; there were significantly fewer systemic embolic events in the rate-control group in trials where more than 50% of patients reported HF (RR= 0.43, 95% CI 0.21-0.89)
    Cordina and Mead,6 20052 RCTs (PIAF,9 AFFIRM11)N = 4312 participants > 18 y with acute, paroxysmal, or sustained AF or atrial flutter, of any duration and any cause (most patients were > 60 y with considerable CV risk factors)No difference in mortality or quality of life between rate- or rhythm-control strategies; hospitalization (P <.001) and adverse events (P <.05) were significantly higher in the rhythm-control group
    De Denus et al,7 20055 RCTs (PIAF,9 RACE,10 AFFIRM,11 STAF,12 HOT CAFE13)N = 5239 participants with first or recurrent AF, mean age 65.1 y, mostly men (65.3%); CAD (29.9%), HTN (52.7%); mean duration of follow-up 1.9 yRate control was significantly better for the combined end point of all-cause death and thromboembolic stroke (NNT = 50); however, for single end points of death and stroke individually, the difference between rate and rhythm strategies was non-significant; differences in serious bleeding (intracranial and extracranial) and systemic embolism were also not significant
    Kumana et al,8 20055 RCTs (PIAF,9 RACE,10 AFFIRM,11 STAF,12 HOT CAFE13)N = 5239 participants with persistent or recurrent AFRate control was significantly better (P <.01) than rhythm control for preventing hospitalizations (NNH = 35 for rhythm control); differences in death, non-CNS bleeding, and ischemic stroke were non-significant

    • AF–atrial fibrillation, CAD–coronary artery disease, CNS–central nervous system, CV–cardiovascular, HF–heart failure, HTN–hypertension, NNH–number needed to harm, NNT–number needed to treat, RCT–randomized controlled trial, RR–relative risk.

  • Table 5

    Pharmacotherapy options: A) Rate control; B) Rhythm control.

    A) DRUGUSUAL DOSEADVANTAGESDISADVANTAGESCOST/30 D
    β-blockers (β-1 cardioselective)

    • Metoprolol (Lopresor, regular and SR)

    • 25-200 mg BID or 100-200 mg SR OD to BID

    • First-line agents in patients with comorbid conditions such as CAD, HF, or LV dysfunction

    • Generally well tolerated

    • Dizziness or fatigue often reported as bothersome side effects

    • Use cautiously in elderly patients (fall risk)

    • Can mask hypoglycemia (use cautiously in diabetes)

    • $10-$33

    • Bisoprolol (Monocor)

    • 2.5-10 mg OD

    • Effective for rate control at rest and with exercise, but no remarkable effects on exercise capacity

    • $10-$15

    Nondihydropyridine CCBs

    • Diltiazem (Cardizem, regular and CD; Tiazac, regular and XC)

    • 120-480 mg OD

    • Preferred for younger patients (less fatigue than with β-blockers)

    • Preferred in COPD or severe asthma

    • Less effective for controlling HR during exercise, but might lead to increased exercise capacity

    • Constipation is a common side effect for verapamil

    • Avoid in patients after MI or HF

    • $25-$60

    • Verapamil (Isoptin SR)

    • 120 mg OD to240 mg SR BID

    • $22-$52

    Other

    • Digoxin (Toloxin)

    		0.0625-0.25 mg OD

    • Can be used as add-on therapy to β-blockers or CCBs if HR is not controlled

    • Use for sedentary patients or LV dysfunction

    • NOT first-line therapy

    • Less effective than β-blockers or CCBs, especially in nonsedentary patients for exercise tolerance

    • Serious toxicity or side effects are possible

    • Considerable amount of drug interactions

    • Associated with increased risk of all-cause mortality regardless of the presence or absence of HF according to AFFIRM trial follow-up analysis17

    • Use cautiously in renal dysfunction

    		$15
    B) DRUGUSUAL DOSEADVANTAGESDISADVANTAGESCOST/30 D
    Class III antiarrhythmics

    • Amiodarone (Cordarone)

    • Loading 800-1600 mg/d for 1-3 wk, then 600-800 mg/d for 1 mo, then 100-400 mg/d; use the lowest effective dose for maintenance

    • Efficacy at 1 y 60%-70% (most effective)

    • CTAF trial18 showed amiodarone was more efficacious at preventing AF than propafenone or sotalol were

    • Possesses both rate- and rhythm-control mechanisms

    • Can be used in patients with renal dysfunction or HF (LVEF ≤ 35%)

    • Safety: many serious side effects that require judicious monitoring (see Table 7)

    • Considerable drug interactions (especially with warfarin; must decrease warfarin dose)

    • Loading dose and extensive titrating schedule required

    • Long half-life (26-107 d)

    • $31-55

    • Dronedarone (Multaq)

    • 400 mg BID

    • Efficacy at 1 y 40%

    • Fewer side effects than amiodarone

    • Less proarrhythmia than with propafenone or sotalol

    • No loading dose required

    • Should NOT be used in patients with permanent AF (increased CV mortality)

    • Relatively new drug; limited experience with efficacy and safety

    • Not covered by provincial formularies (not recommended by CDR)19

    • $150

    • Sotalol (Sotacor)

    • Efficacy at 1 y 30%-50%

    • Possesses both rate- and rhythm-control mechanisms

    • Possesses proarrhythmic qualities

    • CI in patients with CrCl < 40 mL/min (renally eliminated)

    • Bradycardia common in elderly patients

    • Avoid in women > 65 y who are taking diuretics or who have renal impairment owing to increased risk of torsade de pointes

    • $16

    Class I antiarrhythmics

    • Flecainide: (Tambocor))

    • Usual dose: 50-150 mg BID; pill-in-the-pocket dose: 200-300 mg in 1 dose

    • Efficacy at 1 y 30%-50%)

    • Can be used for the pill-in-the-pocket strategy in patients without structural heart disease

    • Should be coupled with an AV nodal blocking agent (β-blocker or CCB) owing to concealed conduction and risk of ventricular tachycardia

    • CI in structural heart disease

    • Can have serious cardiac side effects (cardiac arrest, arrhythmia, AV node block)

    • $60-$85

    • Propafenone (Rythmol)

    • Usual dose: 150 mg)OD-TID; pill-in-the-pocket dose: 450-600 mg in 1 dose

    • Pill-in-the-pocket strategy: first dose is usually given and observed by a cardiologist

    • $21-$45

    • AF–atrial fibrillation, AV–atrioventricular, BID–twice daily, CAD–coronary artery disease, CCB–calcium channel blocker, CD–controlled delivery, CDR–Common Drug Review, CI–contraindicated, COPD–chronic obstructive pulmonary disease, CrCl–creatinine clearance, CV–cardiovascular, HF–heart failure, HR–heart rate, LV–left ventricular, LVEF–left ventricular ejection fraction, MI–myocardial infarction, OD–once daily, SR–sustained release, TID–3 times daily, XC–extended release. Data from Gillis et al1 and Jin and Kosar4

  • Table 7 Amiodarone-monitoring parameters
    PARAMETER MONITOREDFREQUENCY OF OCCURRENCE, %WHAT TO ORDER OR PERFORMHOW OFTEN
    CNS (ataxia, dizziness)4-9Physical examinationEvery follow-up visit
    Corneal deposits4-9Slit lamp examinationAnnually
    Optic neuropathyUnknownOphthalmologic examinationBaseline, every 6-12 mo
    Pulmonary toxicity2-17Chest x-ray scan, pulmonary function tests (and DLCO)Baseline, every 6-12 mo
    Thyroid complications2-6Free T4 level, TSH levelBaseline, every 6-12 mo
    Photosensitivity3-10History, physical examinationEvery follow-up visit
    Blue discoloration of skin (Smurf or Avatar syndrome)< 9History, physical examinationEvery follow-up visit
    GI (nausea, vomiting, anorexia)4-33Weight, physical examination, and historyEvery follow-up visit
    Liver toxicity4-9AST, ALT, bilirubinBaseline, every 6-12 mo

    • ALT–alanine aminotransferase, AST–aspartate aminotransferase, CNS–central nervous system, DLCO–diffusing capacity of lung for carbon dioxide, GI–gastrointestinal, T4–thyroxine, TSH–thyrotropin.

    • Data from Jin and Kosar,4 Siddoway,34 and Pfizer Canada.35

Additional Files

  • CFPlus Additional Information

    This data supplement contains Table 6 from the RxFiles article on rate versus rhythm control in atrial fibrillation.

    Files in this Data Supplement:
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Rate versus rhythm control in atrial fibrillation
Grace Frankel, Rejina Kamrul, Lynette Kosar, Brent Jensen
Canadian Family Physician Feb 2013, 59 (2) 161-168;
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