Circulation, Vol 83, 422-437, Copyright © 1991 by American Heart Association
R Roberts, WJ Rogers, HS Mueller, CT Lambrew, DJ Diver, HC Smith, JT Willerson, GL Knatterud, S Forman and E Passamani
In the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial,
patients received intravenous recombinant tissue-type plasminogen activator
(rt-PA) and were randomized to either a conservative or an invasive
strategy. Within this study, the effects of immediate versus deferred
beta-blocker therapy were also assessed in patients eligible for
beta-blocker therapy, a group of 1,434 patients of which 720 were
randomized to the immediate intravenous group and 714 to the deferred
group. In the immediate intravenous group, within 2 hours of initiating
rt-PA metoprolol was given (5 mg intravenously at 2-minute intervals over 6
minutes, for a total intravenous dose of 15 mg, followed by 50 mg orally
every 12 hours in the first 24 hours and 100 mg orally every 12 hours
thereafter). The patients assigned to the deferred group received
metoprolol, 50 mg orally twice on day 6, followed by 100 mg orally twice a
day thereafter. The therapy was tolerated well in both groups and the
primary end point, resting global ejection fraction at hospital discharge,
averaged 50.5% and was virtually identical in the two groups. The regional
ventricular function was also similar in the two groups. Overall, there was
no difference in mortality between the immediate intravenous and deferred
groups, but in the subgroup defined as low risk there were no deaths at 6
weeks among those receiving immediate beta-blocker therapy in contrast to
seven deaths among those in whom beta-blocker therapy was deferred. These
findings for a secondary end point in a subgroup were not considered
sufficient to warrant a recommendation regarding clinical use. There was a
lower incidence of reinfarction (2.7% versus 5.1%, p = 0.02) and recurrent
chest pain (18.8% versus 24.1%, p less than 0.02) at 6 days in the
immediate intravenous group. Thus, in appropriate postinfarction patients,
beta-blockers are safe when given early after thrombolytic therapy and are
associated with decreased myocardial ischemia and reinfarction in the first
week but offer no benefit over late administration in improving ventricular
function or reducing mortality.
ARTICLES
Immediate versus deferred beta-blockade following thrombolytic therapy in patients with acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) II-B Study
Maryland Medical Research Institute, Baltimore 21210.
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