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Three Part Question

In [patients undergoing cardiac surgery] is prophylactic [Sotalol compared to conventional ß Blockers] more effective in reducing the incidence of [atrial fibrillation].

Clinical Scenario

You are updating a protocol for the prophylaxis of atrial fibrillation after cardiac surgery for your department. For many years the protocol has been to continue the patient's own beta-blockers during the perioperative period, restarting them the day after surgery. A new surgeon in your group suggests that Sotalol, with type III antiarrhythmic properties in addition to Beta-Blockers is superior to this protocol, but other colleagues state that changing the patient's usual medications the day before surgery in this way will lead to a host of complications including bradycardia and hypotension. You resolve to search the literature to see whether it really is worth changing your departmental policy.

Search Strategy

Medline 1966 to Oct 2004 using the OVID interface.
[exp Cardiovascular surgical procedures/OR cardiovascular surgical procedures.mp OR exp Thoracic surgery/OR Thoracic surgery.mp OR exp Coronary Artery Bypass/OR Coronary art$ bypass.mp OR cardiopulmonary bypass.mp OR CABG.mp OR coronary artery surgery.mp OR cardiac surgery.mp OR revascularization.mp OR heart surgery.mp] AND [exp atrial fibrillation/OR atrial fibrillation.mp OR AF.mp OR exp atrial flutter OR atrial flutter.mp OR supraventricular tachycardia.mp OR exp Tachycardia, Supraventricular/ OR SVT.mp] AND [exp sotalol/ OR sotalol.mp]

Search Outcome

A total of 55 articles were identified of which 7 represented the evidence to answer the clinical question. Of note several papers were also found that compared Sotalol to placebo but these were deemed to be irrelevant to our question. A meta-analysis was also found that briefly addressed this topic. These are summarised in the table

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Janssen et al 1986 Holland	N=130 patients undergoing CABG 41 received Sotalol 0.3 mg/kg IV 1 h post op then 80 mg tds daily after 24 h 39 received metropolol 0.1 mg/kg IV 1 h post op then 50 tds daily after 24 h 50 control – No therapy	Single blind PRCT (level 1b)	SVT >100 bpm > 1 min	Sotalol group 1/41 (2.4%) Metoprolol group 6/39 (15.3%) Control group 18/50 (36%) of P=0.05	Lack of continuous ECG monitoring
			Complications	No dose reduction/withdrawal in either group
Surttorp et al, 1990, Netherlands	N=429 74 Sotalol 40 mg tds 133 Sotalol 80 mg tds 66 Propranalol 10 mg qds 156 Propranalol 20 mg qds Starting 4 to 6 h post op	Single blind PRCT (level 1b)	Atrial fibrillation or flutter >30s (at any point of inpatient stay)	Sotalol low dose 10/72 (13.9%). Sotalol high dose 13/119 (10.9%). Propranalol low dose 12/64 (18.8%). Propranalol high dose 19/139 (13.7%) P=NS	Lack of continuous ECG monitoring
			Complication	Drug withdrawn in 2/74. 14/133 sotalol high dose, propranalol 2/66 low dose, 17/156 propranalol high dose
Nystrom et al, 1993, Sweden	N=101 50 sotalol 160mg on pre-op morning then 160mg per day 51 control group (1/2 dose ß Blocker post op if on treatment pre-op or nothing if not on treatment) 40 ß Blocker. 11 not on any treatment	Unblinded PRCT (level 1b)	AF of any duration (up to the end of the 6th post op day)	Sotalol group 5/50 (10%). Control group 15/51 (29%). 4/11 (36%) of those on no treatment, 11/40 (27.5%) of those on ß blocker P=0.028	Lack of continuous ECG monitoring No standardised dose or type of ß blocker
			Complications	Dose reduction or withdrawl in 11 sotalol group and 5 control group
Parikka et al, 1998, Finland	N=191 93 received Metoprolol 25mg tds increased to 50mg tds as tolerated 93 received Metoprolol 25mg tds increased to 80mg tds (Starting on first post-op morning)	Unblinded PRCT (level 1b)	AF>15 min or other sustained arrythmias (at any point during in patient stay)	Metoprolol group 30/93 (32%). Sotalol group 16/98 (16%). P<0.01	Lack of continuous ECG monitoring
			Complications	Withdrawl of drug in one pt. Per group 6 (7%) of metoprolol group and 2 (2%) of sotalol group needed reduction of dosage
Sanjuan et al, 2004, spain	N=253 cardiac patients receiving either CABG or valve surgery 153 received Atenolol 50mg od 100 received 80mg bd sotalol Starting in both 24h pre-op	Unblinded single PRCT (level 1b)	AF>10min at any point during in patient stay	Atenolol group 34/153 (22%). Sotalol group 10/100 (10%) p=0.013	Lack of continuous ECG monitoring Long length of time for atenolol to act
			Complications	Withdrawl of drug in 12. Atenolol group of 8 patients in sotalol group. Dose reduction in 2 of sotalol group
Abdulrahman et al, 1999, USA	N=191 93 Sotalol 40mg, bd for one day then 80mg bd 98 Metoprolol 25mg bd for 1 day then 50mg bd	PRCT Double blind (level 1b)	Incidence of SVT	Sotalol group 9/93 (10%). Metoprolol group 22/98 (22%) p=0.028
			Complications	Non sustained VT seen in 2 in each group. Withdrawl seen in 3 (3.2%) in sotalol group and 7 (7.1%) in Metoprolol group
Auer et al, 2004, Austria	N=253 patients undergoing either CABG or valve surgery, randomised into 4 groups 63 received Amiodarone and Metoprolol (50mg bd) 62 received Metoprolol (50mg bd) 63 received sotalol (80mg tds) 65 received placebo All treatments started 24 to 48 h pre-op and continued for 8 days	PRCT Double blind (level 1b)	Atrial fibrillation >5 min duration or for any length of time requiring intervention	Amiodarone and Metoprolol 19/63 (30.2%) gp p<0.008. Metoprolol only 25/62 (40.3%) p<0.16. Sotalol 20/63 (31.7%) p<0.013. Placebo group 35/65 (53.8%)	No continuous ECG monitoring
			Complications	Dose reduction or withdrawl occurred in: - 3.1% placebo, 3.2% Amiodorone and Metoprolol. 12.7 % sotalol. 16.1% Metoprolol

Comment(s)

All of the seven papers show the reduction in the incidence of post operative atrial fibrillation was greater in those patients treated with prophylactic Sotalol than conventional ß blockade. Five of the seven papers were statistically significant. The remaining 2 papers showed a non-significant trend to a lower incidence of AF with patients treated with Sotalol. Auer et al, looked at 253 patients randomised into 4 groups. The group treated with sotalol alone showed a statistically significant reduction in the incidence of AF compared with placebo, the group treated with ß blocker only showed a non-significant trend to a lower incidence of post op AF. They also showed that patients in both the sotalol and ß-blocker groups had a higher incidence of bradycardia necessitating a dose reduction or withdrawal of the drug but with no difference between them. Patients on active treatments showed a trend towards a shorter hospital stay but no difference was noted between the active groups. Janssen et al, looked at 130 patients undergoing coronary artery surgery. 2.4% of patients treated with sotalol developed post operative AF compared to 15.3% of those treated with metoprolol. The difference was statistically significant. There were no major reported side effects in either group. Parika et al, looked at a total of 191 patients undergoing coronary artery surgery. He showed a significant reduction in the incidence of AF in the group treated with Sotalol (16% vs 32%). He showed doses needed to be increased in 18% of the ß-blocker and 10% of the Sotalol group, the final doses being 54±14 mg Metoprolol group and 40±0 mg in the sotalol group. Medications were stopped in 1 patient per group. Surtorp et al, compared high and low dose treatment regimes in both Sotalol and Propranalol groups. Four hundred and twenty-nine patients were studied. The incidence of AF was 13.9% and 18.8% in the low dose Sotalol and Propranalol groups, respectively, and 10.9% and 13.7% in the high dose Sotalol and Propranalol groups. Although these results show a trend to a lower incidence of AF in both the Sotalol treatment groups they are statistically non-significant. Adverse effects resulting in stopping drug were seen in 2 patients in both low dose treatment regimes (2/74 Sotalol and 2/66 Propranalol) and in 14/133 (high dose Sotalol) and 17/156 (high dose Propranalol) patients. Therefore doubling the dose causes no substantial increase in the preventative effects but produces an increase in the unwanted side effects. Sanjuan et al, looked at 253 patients undergoing Cardiac surgery. AF was seen in 44 patients. The incidence was 10/100 (10%) in the Sotalol group and in 34/153 (22%) in the Atenolol group P=0.013. They also showed that AF resulted in statistically significant longer stays in the CCU and longer hospital stays overall. Adverse effects resulting in withdrawal of treatment was seen in 12 of the Atenolol group and in 16 of the Sotalol group and in 2 of the Sotalol group the drug was reduced. Nystrom et al, looked at 101 patients randomised to Sotalol or control (half dose pre op B blockade or no treatment if not on pre op. ß blockade). AF was seen in 5/50 (10%) of the Sotalol group and in 11/40 (27.5%) of patients on half their pre op ß blocker dose and in 4/11 (36%) patients on no treatment. Eleven patients in the Sotalol group needed dose withdrawal and of these, 5 required withdrawal of the drug, all adverse symptoms resolved following this. Abdulrahman et al, looked at 191 patients undergoing cardiac surgery and were given low dose Sotalol or Metoprolol. AF was seen in 9/93 (10%) of the Sotalol group and in 22/98 (22%) of the Metoprolol group. Dug withdrawal was necessary in 3/93 (3.2%) of the Sotalol group and in 7/98 (7.1%) of the Metoprolol group. Crystal et al, showed a lower incidence of AF in the Sotalol group v B Blocker group when both agents were directly compared (12% vs 22%, OR, 0.50;95% CI 0.34 to 0.74), giving a number needed to treat of 10 to prevent- an additional case of AF using Sotalol versus standard ß-Blockers. With regard to which regime is optimal. Several of these studies seem to use either 40 mg tds or 80 mg bd starting pre-operatively, and doses higher than this caused an excess of side effects. Thus either of these regimes may be considered optimal.

Clinical Bottom Line

Prophylactic Sotalol may be more effective than ß blockers in the prevention of post operative atrial fibrillation in elective patients. Sotalol should not cause an excess of side effects.

References

1. Janssen J, Loomans L, Harink J, Taams M, Brunninkhuis L, van der SP et al. Prevention and treatment of supraventricular tachycardia shortly after coronary artery bypass grafting: a randomized open trial. Angiology 1986;37(1):601-9.
2. Suttorp MJ, Kingma JH, Tjon Joe Gin RM, van Hemel Nm, Koomen EM, Defauw JA, Adan AJ, Ernst SM. Efficacy and safety of low and high dose sotalol versus propranalol in the prevention of superventricular tachyarrythmias early after coronary artery bypass operations. J Thorac Cardiovasc Surg 1990;100:921–926.
3. Nystrom U, Edvardsson N, Breggren H, Pizzarelli GP, Radegran K. Oral sotalol reduces the incidence of atrial fibrillation after coronary artery bypass surgery. Thorac Cardiovasc Surg 1993;41:34–37.
4. Parikka H, Toivonen L, Heikkila L, Virtnaen K, Jarvinen A. A comparison of sotalol and metoprolol in the prevention of atrial fibrillation after coronary artery bypass surgery. J Cardiovasc Pharmacol 1988;31:67–73.
5. Sanjuan R, Blasco M, Carbonell N, Jorda A, Nunez J, Martinez-Leon J, Otero E. Postoperative Sotalol versus atenolol for atrial fibrillation after cardiac surgery. Ann Thorac Surg 2004;77:838–843.
6. Adulrahman O, Dale HT, Levin V, Hallner M, Theman T, Hassapyannes C. The comparative of low dose sotalol vs metoprolol in the prevention of post operative supraventricular arrythmais. Eur Heart J 1999;20:372.
7. Auer J, Webber T, Berent R, Puschmann R, Hartl P, Ng CK, Schwarz C, Lehner E, Strasser U, Lamm G, Eber B. A comparison between oral antiarryhmic drugs in the prevention of post operative atrial fibrillation (SPPAF), a randomised placebo controlled trial. Am Heart J 2004;147:636–643.
8. Crystal E, Connolley SJ, Sleik K, Ginger TJ, Yusuf S. Interventions on prevention of post operative atrial fibrillation in patients undergoing heart surgery. A meta-analysis. Circulation 2002;106:75–80.