EFFECT OF PROPHYLACTIC AMIODARONE ON MORTALITY AFTER ACUTE MYOCARDIAL-INFARCTION AND IN CONGESTIVE-HEART-FAILURE - METAANALYSIS OF INDIVIDUAL DATA FROM 6500 PATIENTS IN RANDOMIZED TRIALS

Background There have been 13 randomised controlled trials of prophyla ctic 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 accu rate 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 accordi ng to standard methods. Findings There were eight post-MI and five CHF trials; nine trials were double-blind and placebo-controlled, and fou r compared amiodarone with usual care. 6553 patients were randomly ass igned treatment, of which 78% were in post-MI trials and 22% in CHF tr ials. 89% had had previous MI. The mean left-ventricular ejection frac tion was 31%, and median frequency of ventricular premature depolarisa tion 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 ran dom-effects approach. Arrhythmic/sudden death was reduced by 29% (0.71 [0.59-0.85], p=0.0003). There was no effect on nonarrhythmic 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 (1 0.7 vs 4.1%), and the best single predictor of risk of arrhythmic/sudd en death among all patients was symptomatic CHF. The excess (amiodaron e minus control) risk of pulmonary toxicity was 1% per year. Interpret ation Prophylactic amiodarone reduces the rate of arrhythmic/sudden de ath in high-risk patients with recent MI or CHF and this effect result s in an overall reduction of 13% in total mortality.