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A Meta-Analysis

Dawn G. Zarembski, PharmD; Paul E. Nolan, Jr, PharmD; Marion K. Slack, PhD; Anthony C. Caruso, MD

Arch Intern Med. 1993;153(23):2661-2667.

Abstract
Background
The prophylactic administration of amiodarone following acute myocardial infarction has been investigated in several small trials. This study combined the results of these small trials in a metaanalysis to determine the effects of prophylactic lowdose amiodarone on mortality following acute myocardial infarction.

Methods
Four prospective, randomized, placebocontrolled trials, which investigated the prophylactic administration of low-dose amiodarone (200 to 400 mg/d) to patients after acute myocardial infarction, were selected from the current literature according to strict inclusion criteria. A total of 1140 patients, 566 in the amiodarone-treated group and 574 in the placebo-treated group, were included in the analysis. Sudden cardiac death, cardiac mortality, and total mortality were the end points of interest. In addition, the effect of impaired left ventricular function (ejection fraction, <45%) on total mortality was assessed. Data were aggregated by using the Mantel-Haenszel method to obtain final summary statistics for these end points.

Results
Patients treated with low-dose amiodarone exhibited a lower incidence of sudden cardiac death (3.1%) and total mortality (6.1%) when compared with patients treated with placebo (6.9% and 11.2%, respectively; both P<.01; and 95% confidence interval [CI], 0.011 to 0.065 and 0.013 to 0.082, respectively). There was no significant difference between the amiodarone- and placebo-treated groups with respect to cardiac mortality (2.6% vs 3.7%, respectively; P=.26; and 95% CI, —0.012 to 0.032). For patients with a left ventricular ejection fraction of less than 45%, total mortality was 5.5% in the amiodarone-treated group and 9.4% in the placebotreated group (P=.30; CI, —0.023 to 0.101).

Conclusions
Although further data from ongoing large, randomized trials are needed, this meta-analysis suggests that the prophylactic administration of low-dose amiodarone to patients following acute myocardial infarction reduces the incidence of both sudden cardiac death and total mortality. The benefits of low-dose amiodarone may be limited to patients with preserved left ventricular function.

(Arch Intern Med. 1993;153:2661-2667)

Author Affiliations
From the Department of Pharmacy Practice, College of Pharmacy (Drs Zarembski, Nolan, and Slack), Section of Cardiology, Department of Internal Medicine, College of Medicine (Dr Caruso), and University Heart Center (Drs Nolan and Caruso), University of Arizona, Tucson.

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