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Three Part Question

In [patients going into AF, 3 days post CABG with good LV and Haemodynamically stable] is [A rate-control strategy compared to a conversion strategy] the best treatment for [time to discharge or survival]

Clinical Scenario

You have just completed a BET comparing Digoxin and Amiodarone for the treatment of AF as the consultants in your hospital have widely varying policies in this area. Unfortunately this BET only found 1 paper and therefore you decide to widen the search to compare rate-controlling drugs versus ant-arrhythmics.

Search Strategy

Medline 1966-07/02 using the OVID interface.
[ cardiac surgical procedure$.mp OR Cardiopulmonary Bypass.mp OR coronary artery bypass.mp OR cardiac disease/su] AND [atrial fibrillation/dt OR arrhythmia/dt OR tachycardia/pc OR tachycardia/th] AND [(sotalol or amiodarone or esmolol or procainamide or digoxin or metoprolol or verapamil or disopyramide).mp]

Search Outcome

89 papers were found of which 82 were deemed to be irrelevant. The remaining 7 papers are shown in the table.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Campbell et al, 1985, Australia	40 patients undergoing cardiac surgery who went into AF with rate over 120bpm 20 patients: Sotalol 1mg/kg iv bolus + 0.2mg/kg iv over 12 hours. If converted –160mg po bd x 2-3 weeks 20 patients: Digoxin 750mcg iv then Disopyramide 2mg/kg iv 2 hrs later. If converted Digoxin 250mcg 250 mcg po ± Disopyramide	PRCT	Conversion to SR	Sotolol group17/20 Digoxin group 17/20	Very high Hypotension rate makes this dose of Sotolol impractical to use in clinical practise Not-blinded
			Time to conversion	Sotolol group 58mins Digoxin group 187mins p<0.05
			Complications	Hypotension in 17/20 of sotolol group but none of Digoxin group Urinary retention in 4 of Digoxin/disopyramide group
Gavaghan et al, 1985, Australia	201 patients after cardiac surgery who all underwent the following protocol: 1. Digoxin 750mcg iv bolus 2. If failure to convert in 2 hours : Disopyramide 2mg/kg iv loading dose over 10 minutes 3. Disopyramide 0.4mg/kg/h or 150mg po qds if AF >48 hrs after operation. Anyone converting within 2 hours remained on Digoxin	Observational Cohort Study	Conversion rate amongst those who had not converted in the first 2 hours	24/156 (15%) after a further 1 hour and 75/156 (48%) after 12 hours 81 patients were unconverted after 14 hrs	No Control group, so inappropriate study design
			Side effects	19% side effects in Disopyramide group Urinary retention 11%. 4 patients developed 1:1 conduction, 1 patient went into VT, and 2 patients had significant hypotension after disopyramide loading
Janssen J et al, 1986, Holland	151 patients undergoing CABG all given prophylactic Metoprolol, Sotalol or Control. 18 out of 50 in the Control group went into AF. These were treated as follows; 10 patients given Sotalol 80mg po 4 patients given Metoprolol 50-150mg po	Sub study of PRCT	Conversion success	100% success in a 14 patients	Very small sub-study of a larger trial
			Time to conversion	Sotalol 2.4 hrs Metoprolol 13.6hrs
Wafa et al, 1989, UK	29 patients post CABG surgery that went into Atrial Tachyarrhythmia with a rate of over 120 bpm for over 15 mins. 15 patients: Flecainide 1mg/kg over 10mins followed by 1.5mg/kg for 1 hour then 250mg/kg/hr for remainder of study 14 patients: Digoxin 500mcg iv followed by 250mcg iv at 6h and 12h	PRCT	Arrhythmia control	Flecainide 10/15 Digoxin 2/14	4 patients who had aortic surgery was initially included and then disappeared from the results as the paper became CABG patients only If AF persisted for more than 45mins both groups also received Verapamil 10mg iv Not blinded
			Reversion to SR	Flecainide 9/15 Digoxin 0/14
			Complications	Flecainide caused hypotension (70mmHg) in 2 patients and nausea in 1 No complications with Digoxin
Hjelms, 1992, Denmark	30 patients with atrial fibrillation after open heart surgery. 15 patients: iv procainamide 15mg/kg, at<25mg/min, followed by 1g po tds x 1 week 15 patients : Digoxin 750mcg to 1000mcg iv loading then maintainance 125-250mcg	PRCT	Immediate conversion	Procainamide87% Digoxin60% P<0.05	Randomisation methodology not described
			Success and Time to conversion	Procainamide 13/15 (40 mins) Digoxin9/15 (540 mins) P<0.05
			Complications	1 x case of VF 1 hour after digoxin bolus 8mmHg mean drop in Systolic BP in Procainamide group
Cochrane et al, 1994, Australia	30 previously stable patients who developed sustained AF >20 mins. following Myocardial revascularisation, valve surgery or combined procedures. 15 patients received a loading dose of 5mg/kg iv over 30 mins then an infusion of 25mg/hr. Rate increased to 40mg/hr if rate >120 in 6 hours. Treatment continued for 24 hours after reversion to SR 15 patients received Digoxin, 500mcg iv over 30 mins. Then 250mcg iv after 2 hours, then 125 mcg iv after 5hrs and 9hrs. Then oral Digoxin started on a per kg basis (formula not given)	PRCT	Reduction in heart rate in the first 6 hours	Amiodarone group 146 to 89 bpm Digoxin group 144 to 95 bpm P=0.33	Randomisation was on the basis of their hospital number – flawed method Not blinded study Small numbers no power study done
			Conversion to SR after 24 hours	Amiodarone group 14 out of 15 Digoxin group 12 out of 15 P=0.87
			Length of hospital stay	Rate control 13.2+/-2 days Antiarrhythmia strategy 9.0+/- 0.7 days P=0.05
Di Biasi et al, 1995, Italy	84 patients after cardiac surgery with Atrial Fibrillation of more than 30 mins. 46 patients : Amiodarone 5mg/kg iv over 15 mins then 15mg/kg over 24hrs 38 patients : Propafenone 2mg/kg over 15 mins and then 10mg/kg over 24hrs	Double blinded PRCT	Conversion rate	Amiodarone 19.5% in 1 hour and 83% after 24hrs Propafenone 45% in 1 hour and 68% after 24 hrs P<0.05 at 1 hr but NS at 24 hrs	Double blinding methodology not described Randomisation was by hospital number – flawed methodology
			Ventricular response	Amiodarone: Decrease of 18% Propafenone: Decrease of 22%
			Complications	Amiodarone:1 hypotension and 4 bradycardia Propafenone: 2 hypotension and 2 bradycardia

Comment(s)

The most remarkable result of this BET is the lack of large double-blinded Prospective Randomised Controlled trials in this very important area. It is difficult to make many conclusions after considering the above studies. Sotalol, Flecainide, and Disopyramide all seem to have significant side effects when compared to Digoxin, although some evidence is presented regarding their increased ability to convert AF. Amiodarone and Digoxin seem to be comparable.

Clinical Bottom Line

There is very little evidence to support any one strategy over another although Amiodarone and Digoxin seem to be low in side effects.

References

1. Campbell TJ, Gavaghan TP, Morgan JJ. Intravenous sotalol for the treatment of atrial fibrillation and flutter after cardiopulmonary bypass. Comparison with disopyramide and digoxin in a randomised trial. Br Heart J 1985;54:86-90.
2. Gavaghan TP, Feneley MP, Campbell TJ, et al. Atrial tachyarrhythmias after cardiac surgery: results of disopyramide therapy. Australian & New Zealand Journal of Medicine 1985;15:27-32.
3. Janssen J, Loomans L, Harink J, et al. Prevention and treatment of supraventricular tachycardia shortly after coronary artery bypass grafting: a randomized open trial. Angiology 1986;37:601-9.
4. Wafa SS, Ward DE, Parker DJ, et al. Efficacy of flecainide acetate for atrial arrhythmias following coronary artery bypass grafting. Am J Cardiol 1989;63:1058-64.
5. Hjelms E. Procainamide conversion of acute atrial fibrillation after open-heart surgery compared with digoxin treatment. Scandinavian Journal of Thoracic & Cardiovascular Surgery 1992;26:193-6.
6. Cochrane AD, Siddins M, Rosenfeldt FL, et al. A comparison of amiodarone and digoxin for treatment of supraventricular arrhythmias after cardiac surgery. Eur J Cardiothorac.Surg 1994;8:194-8.
7. Di Biasi P, Scrofani R, Paje A, et al. Intravenous amiodarone vs propafenone for atrial fibrillation and flutter after cardiac operation. Eur J Cardiothorac Surg 1995;9:587-91.