Thrombolysis In Myocardial Infarction trial, phase II-B - TIMI 2B


Immediate vs. delayed beta-blockade for death/reinfarction in acute MI.


Whether the use of immediate beta-blockade may decrease the incidence of cardiac rupture.

Study Design

Study Design:

Patients Screened: 2,984
Patients Enrolled: 1,434
Mean Follow Up: 1 year
Mean Patient Age: 55
Female: 15
Mean Ejection Fraction: 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.

Patient Populations:

<75 years of age
Treated <4 hours after the onset of chest pain
Diagnosis of AMI based on chest pain suggesting acute myocardial ischemia lasting >30 minutes
ST-segment elevation (0.1 mV) in at least two electrically contiguous ECG leads


History of a cerebrovascular event
Blood pressure of >180 mm Hg systolic or >110 mm Hg diastolic
Bleeding disorder
Surgery within the previous two weeks
Recent prolonged cardiopulmonary resuscitation
Percutaneous transluminal coronary angioplasty (PTCA) or severe trauma within six months
Previous coronary artery bypass graft (CABG)
Prosthetic heart valve replacement
Left bundle branch block
Dilated cardiomyopathy
Other serious illness

Primary Endpoints:

Global left ventricular ejection fraction at the time of hospital discharge.

Secondary Endpoints:

Resting left ventricular ejection fraction at six weeks, exercise left ventricular ejection fraction both at hospital discharge and at six weeks, regional left ventricular ejection fraction in the infarcted area at rest and on exercise before hospital discharge and at six weeks, myocardial ischemia.

Drug/Procedures Used:

Immediate metoprolol: 3 doses of 5 mg IV, followed by 50 mg bid on day 1 then 100 mg bid; deferred metoprolol: oral metoprolol 50 mg bid on day 6 followed by 100 mg bid thereafter.

Concomitant Medications:

rt-PA in all patients <4 hours after the onset of symptoms, (1) during the first six months of recruitment, 150 mg/6 hours, (2) because of an unacceptable frequency of hemorrhagic complications, subsequent patients received a dose reduced to 100 mg/6 hours administered as an IV bolus of 6 mg and a constant infusion of 54 mg during the first hour, 20 mg during the second hour, and 5 mg during each of the next 4 hours; lidocaine, 1-1.5 mg/kg bolus injection followed by an infusion of 2 to 4 mg/minute for a minimum of 24 hours; heparin initiated at the same time as rt-PA, 5000 U IV followed by a 5-day constant infusion initially at 1000 U/hour, but adjusted to maintain the activated partial thromboplastin time of 1.5-2.0 times control values; in the first 93 patients, aspirin, 80 mg/day was initiated on day 1 and for the remaining patients, aspirin, 80 mg/day was initiated on day 2

Principal Findings:

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% vs. 5.1%, p = 0.02) and recurrent chest pain (18.8% vs. 24.1%, p less than 0.02) at 6 days in the immediate intravenous group.


In appropriate postinfarction patients, beta-blockers are safe when given early after thrombolytic therapy. Beta-blockers are associated with decreased myocardial ischemia and reinfarction in the first week but offer no benefit over late administration either in improving ventricular function or reducing mortality.


1. Circulation 1991;83:422-37. Final results

Clinical Topics: Atherosclerotic Disease (CAD/PAD)

Keywords: Thrombolytic Therapy, Coronary Artery Disease, Chest Pain, Heart Rupture, Ventricular Function, Electrocardiography, Metoprolol

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