Should beta-blockers be given immediately and concomitantly with thrombolytic therapy in acute myocardial infarction?

T he efficacy of /3-blockers in the setting of acute myocardial infarction has been extensively studied.Over 50 randomized clinical trials involving more than 50,000 patients have been car- ried out to evaluate either /3-blockers begun intrave- nously early after infarction or their long-term chronic oral use as secondary prevention.Pooled data from trials in which therapy was usually initiated before hospital discharge and generally maintained for at least 1 year indicate that mortality can be reduced by an average of 21% and reinfarction by 24%.1 Trials of the early use of intravenous /3-blockers on mortality in the prethrombolytic era have been less impressive.Pooled data from 27 trials involving approximately 27,000 patients reveal only a 13% reduction in mortality (p<0.01).2The three largest of these trials were the Goteborg Metoprolol Trial,3 the Metoprolol in Acute Myocardial Infarction (MIAMI) See p 422 Trial,4 and the first International Study of Infarct Survival (ISIS-I) Trial.5In the Goteborg Trial3 intravenous and then oral metoprolol was used.Among 697 patients random- ized to placebo, the 7-day mortality rate was 3.3% and the mortality rate in the 698 patients receiving metoprolol was 2.6%.6 Initiation of therapy took place after a mean time lapse of 11.3 hours.This led the same group of investigators to carry out a much larger study, the MIAMI Trial,4 with the express purpose of studying very early intervention.The MIAMI Trial4 involved 2,901 patients who received placebo and 2,877 patients randomized to receive intravenous and then oral metoprolol.The median delay time from onset of symptoms to ran- domization was 7 hours.Seven-day mortality was