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Three Part Question

In [patients with atrial fibrillation and who are not significantly cardiovascularly compromised] is [amiodarone better than placebo] at [reverting the patient back to sinus rhythm]?

Clinical Scenario

A 50 years old man attends the Emergency Department with a 12 hours history of palpitations; he complains of slight shortness of breath on walking upstairs and on clinical examination is found to be in atrial fibrillation (rate 140/min.) with a normal BP, fine bilateral basal crepitations and an otherwise normal ECG. You wonder if amiodarone increases the chances of spontaneous cardioversion back to sinus rhythm.

Search Strategy

Medline 1966- 09/05 using the OVID interface.
[(exp Atrial Fibrillation OR atrial fibrillation.mp OR AF.mp) AND (exp Amiodarone OR {amiodarone OR Cordarone}.mp) AND (exp Placebos OR placebo.mp)].
Embase 1974-06/2005 using the Dialog DataStar interface.
[(atrial ADJ fibrillation) AND (amiodarone) AND (placebo)].
The Cochrane library was also searched (accessed 02/2005).
References of the articles were scrutinised for further references.

Search Outcome

The Medline search produced 77 papers, Embase 182, and Cochrane 122; from these, 2 meta-analyses were found to be relevant (all other studies found were referenced by the meta-analyses).
Reference review discovered no further articles.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Chevalier P 2003	6 RCTs with 595 patients with AF of less than 1 week's duration, treated with either amiodarone or placebo	Meta-analysis	1. Rate of cardioversion after 24 hours.	1. Amiodarone is more effective than placebo at cardioverting patients after 24 hours of treatment.	1. Dosage regimes varied. 2. Only short-term effects were studied.
			2. Adverse events over 24 hours (arrhythmias, hypotension, heart failure)	2. Adverse events were rare at this stage so it was difficult to compare rates between the groups.
Letelier LM 2003	21 RCTs with 1930 patients with AF of any aetiology (except uncontrolled thyroid disease) and duration.	Meta-analysis	1. Rate of cardioversion over 4 weeks.	1. Amiodarone is significantly better than placebo for AF of both > and < 48 hours' duration.	1. Dosage regimes varied. 2. Still only short-term effects were studied. 3. Outcomes were measured at different times by different trials (<24 hours in 14; 48-96 hours in 3, & 3-4 weeks in 4)
			2. Adverse events over 4 weeks (mortality, arrhythmias, hypotension, cerebrovascular events, MIs and heart failure)	2. Adverse events were rare so it was difficult to compare rates between the groups.

Comment(s)

Both meta-analyses were included in this BET because each one focussed on a slightly different aspect of atrial fibrillation, although they shared analysis of 5 studies. Chevalier analysed patients with AF of less than one week's duration and studied cardioversion rates after 24 hours of treatment; Letelier and colleagues assessed patients with AF of any duration, although they undertook a subgroup analysis of AF of less than compared with more than 48 hours. Although both studies indicate that amiodarone improves the rate of spontaneous cardioversion, irrespective of the duration of AF, and that the adverse events are not significantly increased in the short-term, neither study followed up patients beyond 4 weeks. Further research is needed to assess the long-term morbidity and mortality associated with continued amiodarone use.

Clinical Bottom Line

Amiodarone is better than placebo at cardioverting patients with AF of any duration with no significant increase in adverse effects over the first 4 weeks of treatment.

References

1. 1. Chevalier P, Durand-Dubief A, Burri H, Cucherat M, Kirkorian G, and Touboul P. Amiodarone versus placebo and class Ic drugs for cardioversion of recent-onset atrial fibrillation: a meta-analysis. J Am Coll Cardiol. 2003; 41; 255-262.
2. Letelier LM, Udol K, Ena J, Weaver B, and Guyatt GH. Effectiveness of amiodarone for conversion of atrial fibrillation to sinus rhythm: a meta-analysis. Arch Intern Med. 2003; 163; 777-785.