Effect of prophylactic amiodarone on mortality after acute myocardial infarction and in congestive heart failure: meta-analysis of individual data from 6500 patients in randomised trials

BACKGROUND There have been 13 randomised controlled trials of prophylactic amiodarone in patients with recent myocardial infarction (MI) or congestive heart failure (CHF). None of these was powered to detect a mortality reduction of about 20%. We undertook a meta-analysis, based on data from individual patients, to provide a more sensitive and accurate assessment of the benefits and risks of prophylactic amiodarone. METHODS Individual data from the studies were abstracted according to a predefined protocol. The summary odds ratios were calculated according to standard methods. FINDINGS There were eight post-MI and five CHF trials; nine trials were double-blind and placebo-controlled, and four compared amiodarone with usual care. 6553 patients were randomly assigned treatment, of which 78% were in post-MI trials and 22% in CHF trials. 89% had had previous MI. The mean left-ventricular ejection fraction was 31%, and median frequency of ventricular premature depolarisation 18 per h. Total mortality was reduced by 13% (odds ratio 0.87 [95% CI 0.78-0.99], p = 0.030) based on classic fixed-effects meta-analysis and by 15% (0.85 [0.71-1.02], p = 0.081) with the more conservative random-effects approach. Arrhythmic/sudden death was reduced by 29% (0.71 [0.59-0.85], p = 0.0003). There was no effect on non-arrhythmic deaths (1.02 [0.87-1.19], p = 0.84). There was no difference in treatment effect between post-MI and CHF studies. The risk of arrhythmic/sudden death in control-group patients was higher in CHF than in post-MI studies (10.7 vs 4.1%), and the best single predictor of risk of arrhythmic/sudden death among all patients was symptomatic CHF. The excess (amiodarone minus control) risk of pulmonary toxicity was 1% per year. INTERPRETATION Prophylactic amiodarone reduces the rate of arrhythmic/sudden death in high-risk patients with recent MI or CHF and this effect results in an overall reduction of 13% in total mortality.