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Three Part Question

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

Clinical Scenario

A man attends the Emergency department with a 12 hours history of palpitations. He denies any history of previous ischaemic heart disease. He complains of no other symptoms other than mild dizziness. On clinical examination he has a normal BP, no signs of heart failure and an ECG shows him to be in AF with a rate of 140/min. You have read some studies that have shown both intravenous and oral flecainide is effective at converting AF to sinus rhythm, but wonder which route is more effective and safe.

Search Strategy

Medline 1966- 09/ 2005 using the Ovid interface.
Embase 1974-06/2005 using Dialog DataStar interface.
The Cochrane library was also searched (accessed 02/2005).
References of the articles retrieved were searched to identify further references.
Medline:[(exp Atrial fibrillation OR atrial fibrillation.mp OR AF.mp) AND (exp flecainide OR flecainide.mp)].
Embase:[(atrial ADJ fibrillation) AND (flecainide) AND (oral AND intravenous)]

Search Outcome

The Medline search produced 327 papers, Embase 245 papers, and Cochrane 63.
Reference review discovered no additional papers.
A total of 2 papers were found to be of sufficient quality and relevant to the 3 part question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Crijns 1988	40 patients with AF (>70/min) of any duration, randomised to oral flecainide (200mg followed by up to 2 doses of 100mg at hourly intervals if still in AF) or iv flecainide (2mg/kg).	RCT (unblinded)	1. Rate of cardioversion at 24 hours.	1. AF < 24 hours (n=27) oral – 71.4% iv – 76.9% (N/S) AF > 24 hours (n=13) None cardioverted in either group.	1. not blinded. 2. very small study (no cardioversions in patients with AF > 24 hours runs counter to larger studies of both iv and po flecainide). 3. short term outcomes.
			2. Time of cardioversion.	2. oral – 104 +/- 86 mins. iv – 14.1 +/- 8 mins
			3. Adverse events.	3. No serious events reported.
			A subgroup analysis was performed on those with AF <24 hours and those with AF >24 hours.
Alp 2000	79 patients with AF < 48 hours (>100/min) randomised to receive flecainide, either 4mg/kg (max 300mg) orally or 2mg/kg (max 150mg) iv.	RCT (double blinded)	1. Rate of cardioversion at 8 hours.	1. oral – 75% iv – 72% (N/S)	1. Patients were on a Coronary Care Unit so uncertain relevance to an Emergency Department population. 2. short term outcomes.
			2. Time of cardioversion.	2. oral – 110 mins (SD 82.3) iv – 52 mins (SD 54.5) (p<0.002)
			3. Adverse events.	3. Nodeaths or serious events reported.

Comment(s)

Both of these studies agree that flecainide is equally effective for stable AF (<48 hours duration) irrespective of route (oral or intravenous). It was interesting to note that doses of 2-4mg/kg iv and 150-400mg po had similar rates at 8-24 hours ((72-77%). Although the data suggested that the oral route takes longer to be effective, a more clinically relevant measure would have been from decision to treat to cardioversion; the time difference between the routes may be less than reported because the oral route is more rapid to administer. The patients were followed up for too short a period to assess long term safety although these papers failed to identify any serious, immediate adverse events. Further research is needed to assess safety of both routes of administration of flecainide for stable AF.

Clinical Bottom Line

Oral and intravenous flecainide is equally effective for cardioverting stable AF of < 48 hours duration. Further research is required to assess the safety of flecainide in stable AF, and its effect when AF has been present for more than 48 hours.

References

1. Crijns HJGM, van Wijk LM, van Gilst WH, Kingma JH, van Gelder IC, and Lie KI. Acute conversion of atrial fibrillation to sinus rhythm: clinical efficacy of flecainide acetate. Comparison of two regimes. Europ Heart J. 1988; 9; 634-638.
2. Alp NJ, Bell JA, and Shahi M. Randomised double blind trial of oral versus intravenous flecainide for the cardioversion of acute atrial fibrillation. Heart. 2000; 84; 37-40.