Amiodarone to Prevent Atrial Fibrillation

Source: Roy D, et al. N Engl J Med 2000;342:913-920.

Preventing atrial fibrillation (af) recurrences has been a challenge because they are frequent. Drug therapy has been unimpressive. Also, most of the drugs used have considerable potential toxicity. Roy and colleagues reported on the results of the Canadian Trial of Atrial Fibrillation, which is a prospective, randomized, multicentered study designed to test the hypothesis that low-dose amiodarone is more effective than sotalol or propafenone for preventing AF recurrence. Entry criteria were at least one episode of AF within six months that lasted at least 10 minutes and was documented on electrocardiogram (ECG). Excluded were acute infarction patients, post-cardiac surgical patients, class III or IV cardiac patients, and those with an obvious reversible cause of AF and any contraindications to the study drugs. About half the patients were assigned to amiodarone (200 mg/day after loading), one-quarter to sotalol, and one-quarter to propafenone. Drugs were started before elective cardioversion when necessary and sotalol and propafenone could be substituted for each other if initial therapy was unsuccessful. Follow-up start-ed at day 21 and the primary end point was AF recurrence. Over the 468-day mean follow-up, 35% of those assigned to amidarone recurred vs. 63% assigned to the other drugs (P < 0.001). Cardiovascular events were similar in the two groups, except that stroke was less common in those treated with amiodarone (1 vs 9; P = 0.01). Drug discontinuation was less on amiodarone (34% vs 46%; P = 0.01). Drug discontinuation for lack of efficacy was less in amiodarone (8% vs 28%; P < 0.001). Adverse events were somewhat more common on amiodarone (18% vs 11%; P = 0.06). No particular clinical or echocardi graphic characteristic subgroup benefited more or less from amiodarone. Roy et al concluded that amiodarone is superior to sotalol and propafenone for the prevention of recurrent AF.

Comment by Michael H. Crawford, MD

Preventing recurrent AF after cardioversion is a major concern because of the expense and risk of cardioversion, the potential consequences of recurrent AF, and the poor performance and risk of type I antiarrhythmic drugs. Recurrence rates for type I agents have been about 60% at one year, which is what this study found with propafenone and the type III agent sotalol. The results with amiodarone were almost twice as good, with a 35% one-year recurrence rate. The relative efficacy of sotalol and propafenone was the same.

The major concern with amiodarone is long-term toxicity, which was somewhat greater than the other two drugs in this trial. However, there were no serious or life threatening complications and, interestingly, more patients were still on amiodarone at the end of a year (72%) than the other two drugs (58%). Also, because AF was prevented more effectively by amiodarone, there were less strokes on it. Cardiac arrest due to torsade de pointes only occurred in one patient taking propafenone. Of course, the longer term potential adverse effects of amiodarone are a concern, but a larger, longer trial will be necessary to assess this issue because of the good prognosis of most patients with isolated AF.

The study was not powered for mortality, and little was observed. Also, there was no placebo group, because these were patients in whom the physician had already decided to cardiovert and try to maintain in sinus rhythm. In addition, the drug therapy was not blinded because of the differences in dosing regimens and the complexity of these agents. However, the primary end point was objectively documented recurrent AF, and unlikely influenced by the lack of blinding.

This study supports the concept that if drug therapy is deemed desirable for a patient undergoing cardioversion for AF, then low-dose amiodarone should be the first-choice agent currently, unless there are contraindications to its use. The real issue given the potential toxicity of amiodarone (and other antiarrhythmic agents) is whether prophylactic drug therapy should be given at all without a trial of no drug. Unfortunately, we do not know how many or which patients will recur on no therapy. Those who do will have to undergo cardioversion again and risk the complications of recurrent AF. There is evidence that the more AF you have, the less likely you will stay in sinus rhythm. This would argue for an aggressive approach with amiodarone for almost all. Perhaps the ongoing AF Follow-up Investigation of Rhythm Management Study by the NHLBI will answer this question. My current practice is to use amiodarone prophylaxis in higher risk patients for stroke and try no therapy first after cardioversion in lower risk patients.

The most effective agent for prevention of atrial fibrillation recurrence is:

a. amiodarone.

b. propafenone.

c. sotalol.

d. flecainide.