Authors' objectives

To compare the efficiency of sotalol versus amiodarone in preventing the occurrence of atrial fibrillation or flutter (AFF) after coronary artery bypass graft (CABG) surgery.

Searching

MEDLINE was searched from 1985 to 2000 for publications in the English language, using the terms 'coronary artery bypass', 'atrial fibrillation', 'atrial flutter' and 'supraventricular arrhythmias'. The reference lists from the retrieved articles were also examined.

Study selection

Assessment of study quality

The authors do not state that they assessed validity.

Data extraction

The authors do not state how the data were extracted for the review, or how many of the reviewers performed the data extraction. Data were extracted on:

the type of study, i.e. primary intervention, intention to treat, use of placebo versus standard treatment, whether double-blinded;

the participants' characteristics, e.g. mean age, and incidence and type of supraventricular arrhythmia,

the form of treatment (sotalol or amiodarone) and the drug regimen, including the start of treatment and the time monitored;

the effect of treatment on AFF and adverse drug reactions; and

the length of hospitalisation.

A weighted average rate difference (RD), i.e. the difference between the percentage of patients with AFF in the treatment and in the control groups, was calculated for each of the drug trials.

Methods of synthesis

Results of the review

Ten RCTs were included in the review, of which 5 (n=539) and 5 (n=764) used amiodarone.

The intention-to-treat format was reported for only one included study. The formal test of homogeneity found similar results from all of the included studies, and the results were reinforced by the graphical analysis. No adjustment was necessary because the inter-study variability was minimal

The pooled data found that each drug was significantly better than placebo in reducing the incidence of post-operative AFF: the RD was -21.5% (95% confidence interval, CI: -28.3, -14.6, p<0.001) for sotalol and -14.1% (95% CI: -20.1, -8.1, p<0.001) for amiodarone. While the overall reduction in AFF was greater for sotalol than for amiodarone, this difference was not statistically significant. The results were similar between the two drug groups for adverse drug reactions causing drug termination: the RD was 9.7% (95% CI: 0.086, 19.3) for sotalol and 1.95% (95% CI: -2.5, 11.0) for amiodarone. This difference was significant in the sotalol group, but not in the amiodarone group (p=0.12).

No statistically-significant differences were found between amiodarone and sotalol for length of stay: -0.13 days (95% CI: -0.33, 0.07, p=0.20) for sotalol and -0.18 days (95% CI: -0.38, 0.02, p=0.08) for amiodarone. A subgroup analysis of the 10 studies noted trends in the treatment effect, as influenced by gender distribution and average age of the study population, although these data were not reported in the article. Studies with the highest percentage of men tended to show the smallest treatment effects, while those with older participants showed a trend towards being less responsive to drug treatment.

Cost information

The authors state that studies have reported that AFF can increase length of stay by up to 4.9 days at an increased cost of $10,055 per patient, suggesting that prophylactic treatment for AFF is a cost-effective measure for managing post-operative arrhythmias. Intravenous administration of amiodarone is associated with an increased cost ranging from $500 to $1,000 a day. A 2-day intravenous dose plus oral amiodarone can result in an increased cost of $1,500 to $2,000 per patient. When compared to a 7-day supply of oral sotalol (80 mg) at the average wholesale price of $32.86 per patient, there is a considerable cost difference.

Authors' conclusions

The review suggests that both drug regimens are effective in reducing AFF following heart surgery. The data did not show either drug to be superior in reducing the incidence of post-operative AFF or length of stay. Amiodarone had fewer side-effects requiring drug termination than sotalol, but when compared with each other, no differences were observed.

CRD commentary

The review question and the study selection criteria were clear. The literature search was limited to one source (MEDLINE) and English language publications, so it is possible that studies may have been missed. Apart from checking the reference lists from additional relevant studies, no other means of identifying additional sources were described. The authors did not supply details of how the study selection and data extraction processes were conducted, or on whether or how validity assessments were carried out.

There were occasional typographical errors in the article, e.g. in the reporting of the results of some of the statistical analyses: the frequency of adverse drug reactions for amiodarone were (CI: -0.48, 4.38) in the abstract, (CI: 2.5, 11.0%) in the results section of the article, and (CI: -2.5, 11.%) in table 3. In addition, there were also discrepancies in the spelling of acronyms, e.g. SVT in table 1 instead of SVA, which is very confusing for the reader.

The authors frequently compared the pooled results of amiodarone and sotalol, but these drugs have not been compared in a RCT in this review. Further information on the relative benefits and disadvantages of the two drugs, and indications for their use, were given in the 'Discussion' section of the article.

The authors' conclusions that sotalol and amiodarone are equally effective is not warranted, as they have not been compared directly in this review.

Implications of the review for practice and research

Practice: The authors state that although either sotalol or amiodarone are equally effective in reducing arrhythmias in patients undergoing heart bypass surgery, amiodarone is more costly than sotalol. As the two drugs each have different metabolic indications for use, these should be balanced against cost considerations before one or the other is employed.

Reviewer's statement: Sotalol and amiodarone have not been compared directly in this review, so the authors cannot conclude that they are equally effective.

Research: The authors state that given the wide degree of variation between the included studies in a number of the key variables, a true comparative study should be undertaken to compare the efficacy of the two drug regimens. Subgroup analysis suggesting that male participants were not as responsive to therapy as female participants, and that the older the patient is, the less responsive they are to therapy, should also benefit from further investigation.

Bibliographic details

Wurdeman R L, Mooss A N, Mohiuddin S M, Lenz T L. Amiodarone vs sotalol as prophylaxis against atrial fibrillation/flutter after heart surgery: a meta-analysis. Chest 2002; 121(4): 1203-1210. [PubMed: 11948054]

Original Paper URL

http://journal.publications.chestnet.org/article.aspx?articleid=1080502

Other publications of related interest

1. Cochran WG. The combination of estimates from different experiments. Biometrics 1954;10:101-29. 2. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-88. 3. D'Agostino RB, Weintraub M. Meta-analysis: a method for synthesising research. Clin Pharmacol Ther 1995;58:605-16.

Indexing Status

Subject indexing assigned by NLM

MeSH

Aged; Amiodarone /adverse effects /therapeutic use; Anti-Arrhythmia Agents /adverse effects /therapeutic use; Atrial Fibrillation /diagnosis /prevention & control; Atrial Flutter /diagnosis /prevention & control; Coronary Artery Bypass; Female; Humans; Male; Middle Aged; Postoperative Complications /diagnosis /prevention & control; Randomized Controlled Trials as Topic; Sotalol /adverse effects /therapeutic use

AccessionNumber

12002001134

Database entry date

31/01/2003

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.