Abstract :
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.
