Maintaining sinus rhythm: Choosing the right drug
Without chronic antiarrhythmic therapy, only about 30% of patients with AF will remain in normal sinus rhythm after a year.20 Of the drugs that can be used to maintain sinus rhythm—amiodarone, disopyramide, flecainide, propafenone, and sotalol—amiodarone is the most effective. In the Canadian Trial of Atrial Fibrillation,21 403 patients treated with amiodarone, sotalol, or propafenone were followed for 16 months. The recurrence rate for the amiodarone group was 35%, compared with 63% for those being treated with sotalol or propafenone.
Adverse effects to consider
Amiodarone is less proarrhythmic than the other antiarrhythmic agents, but it is associated with serious noncardiac toxicities, including pulmonary, thyroid, neurologic, hepatic, optic, and dermatologic adverse effects. In addition, amiodarone can increase plasma levels of several drugs, including digoxin and warfarin, and periodic monitoring of the doses of these medications is essential. Adding enalapril, an angiotensin-converting enzyme inhibitor, or irbesartan, an angiotensin receptor blocker, can enhance the efficacy of amiodarone in maintaining normal sinus rhythm after cardioversion.
Thus, the choice of medication to maintain sinus rhythm should be individualized, based on the patient’s underlying cardiac condition and the safety profile of the antiarrhythmics being considered. (TABLE 3). The ACC/AHA/ESC guidelines recommend class 1C agents flecainide and propafenone as first-line therapy for maintaining sinus rhythm in patients with structurally normal hearts.1 But because of their proarrhythmic and negative ionotropic effects, class 1C agents should not be given to patients who have heart failure or ischemia. Amiodarone and dofetilide are the preferred agents for maintaining sinus rhythm in patients with heart failure and severe left ventricular hypertrophy, and dofetilide, amiodarone, and sotalol are best suited for patients with ischemic heart disease.
Pill-in-the-pocket. For selected patients with paroxysmal AF and a structurally normal heart, a “pill-in-the-pocket” strategy is an option—provided it has been tried in the hospital and proven to be safe. A patient using this strategy would self-administer a single dose of a class 1C antiarrhythmic agent—eg, 600 mg propafenone or 300 mg flecainide—at the onset of an acute episode of AF. Concomitant administration of a beta-blocker or calcium channel blocker is recommended to prevent development of atrial flutter with rapid AV conduction.
TABLE 3
Maintaining sinus rhythm in patients with AF
| DRUG | DAILY DOSE | INDICATION | POTENTIAL ADVERSE EFFECTS | COMMENTS |
|---|---|---|---|---|
| Amiodarone | 100-400 mg | Hypertension with LVH, impaired LV function, HF, ischemic heart disease | Photosensitivity, pulmonary toxicity, polyneuropathy, GI upset, bradycardia, torsades de pointes (rare), hepatic toxicity, thyroid dysfunction, eye complications | Use with care in patients with asthma or bradycardia. |
| Disopyramide | 400-750 mg | Asthma, thyroid disease | Torsades de pointes, HF, glaucoma, urinary retention, dry mouth | |
| Dofetilide | 500-1000 mcg | Cardiomyopathy, ischemic heart disease, significant LV dysfunction | QT prolongation, torsades de pointes | In inpatient setting, adjust dose for renal function and QT-interval response. Avoid in patients with renal failure. |
| Flecainide | 200-300 mg | First-line therapy for patients with a structurally normal heart | VT, HF, conversion to atrial flutter with rapid conduction through AV node | May be used in patients with asthma and thyroid disease. |
| Propafenone | 450-900 mg | First-line therapy for patients with a structurally normal heart | VT, HF, conversion to atrial flutter with rapid conduction through AV node | Use with care in patients with asthma or bradycardia. |
| Sotalol | 160-320 mg | Ischemic heart disease, thyroid disease | Torsades de pointes, HF, bradycardia, exacerbation of chronic obstructive or bronchospastic lung disease | In inpatient setting, adjust dose for renal function and QT-interval response. Avoid in patients with renal failure. |
| AF, atrial fibrillation; AV, atrioventricular; GI, gastrointestinal; HF, heart failure; LV, left ventricular; LVH, left ventricular hypertrophy; VT, ventricular tachycardia. | ||||
| Adapted from: Fuster V, et al. Circulation. 2006.1 | ||||
Using anticoagulation as prophylaxis
Judicious use of antithrombotic prophylaxis can significantly reduce the incidence of strokes associated with AF, regardless of whether you pursue a rate-control or rhythm-control strategy. Despite clear evidence of the efficacy of warfarin and aspirin in this patient population, anticoagulation remains underused in clinical practice.
If AF recurs or the patient develops chronic AF, the AFFIRM trial suggests the need for long-term anticoagulation for patients with thromboembolic risk factors.9
Adjusted-dose warfarin gets best results. A meta-analysis of 29 randomized trials from 1996 to 2007 involving 28,044 patients (mean age, 71 years; mean follow-up, 1.5 years) assessed the benefits of antithrombotic therapy for patients with AF.22 Compared with the controls, adjusted-dose warfarin (6 trials, 2900 participants) and antiplatelet agents (8 trials, 4876 participants) reduced stroke by 64% (95% confidence interval [CI], 49%-74%) and 22% (95% CI, 6%-35%), respectively.
Adjusted-dose warfarin was substantially more effective than antiplatelet therapy (12 trials, 12,963 participants; relative risk reduction, 39% [95% CI, 22%-52%]). The absolute risk reduction (ARR) with adjusted-dose warfarin in all strokes was 2.7% per year (number needed to treat [NNT] for 1 year to prevent 1 stroke was 37) for primary prevention and 8.4% per year (NNT, 12) for secondary prevention. Aspirin showed an ARR of 0.8% per year (NNT, 125) for primary prevention trials and 2.5% per year (NNT, 40) for secondary prevention trials. The absolute increase in major extracranial hemorrhage was small (≤0.3% per year).22