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 Academic Article uri icon

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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.

authors

  • Connolly, Stuart
  • Cairns, J
  • Gent, Michael
  • Roberts, R
  • Yusuf, Salim
  • Julian, DG
  • Camm, AJ
  • Frangin, G
  • Janse, MJ
  • Munoz, A
  • Schwartz, PJ
  • Simon, P
  • Rosenbaum, MB
  • Elizari, MV
  • Cagide, A
  • Girotti, LA
  • Martinez, JM
  • Carbajales, J
  • Scapin, O
  • Garguichevich, J
  • Hauad, S
  • Belziti, C
  • Sinisi, A
  • Ceremuzynski, L
  • Budaj, A
  • Kleczar, E
  • Nartowicz, E
  • SmielakKorombel, J
  • Dyduszynski, A
  • Maciejewicz, J
  • Kokowicz, P
  • NavarroLopez, F
  • Cosin, J
  • Marrugat, J
  • Guindo, J
  • deLuna, AB
  • Pfisterer, M
  • Osswald, S
  • Burckhardt, D
  • Burkart, F
  • Hockings, B
  • George, T
  • Mahrous, F
  • Taylor, R
  • Hajar, H
  • Singh, S
  • Fletcher, R
  • Fisher, S
  • Singh, B
  • Doval, H
  • Nul, D
  • Grancelli, H
  • Perrone, S
  • Bortman, G
  • Curiel, R
  • Ramos, J
  • Gambarte, A
  • Gentile, A
  • Sirena, J
  • Tibaldi, M
  • Toplikar, J
  • Nicklas, J
  • McKenna, W
  • Stewart, R
  • Mickelson, J
  • Das, S
  • Schork, A
  • Krickler, S
  • Quain, L
  • Morady, F
  • Pitt, B
  • Hamer, A
  • Arkles, L
  • Johns, J
  • Morrison, L
  • Roberts, J

publication date

  • November 1997