First International Study of Infarct Survival - ISIS-1


Early beta-blockade for mortality after acute myocardial infarction.


To assess the effects of early beta-blockade following acute myocardial infarction.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 16,027
Mean Follow Up: 20 months
Mean Patient Age: 58

Patient Populations:

Acute MI within 12 hours

Primary Endpoints:

Vascular mortality

Drug/Procedures Used:

Atenolol 5-10mg IV over 5 minutes, followed by 100 mg/day for 7 days.

Principal Findings:

A total of 8037 patients were randomized to atenolol, and 7990 to control.

Vascular mortality during the treatment period (days 0-7) was significantly lower (2p less than 0.04) in the treated group, (3.9% versus 4.6%), but this 15% relative difference had wide 95% confidence limits (from 1 to 27%). No subgroups were identified in which the relative reduction in days 0-7 was clearly better, or clearly worse, than 15%.

At one year, overall vascular mortality was significantly lower for the atenolol group (life-table estimates: 10.7% atenolol vs 12.0% control; 2p less than 0.01).

A substudy reviewed records for 193 of 217 early deaths (79 allocated to atenolol and 114 allocated to control). There was a lower rate of deaths attributed to myocardial rupture or electromechanical dissociation in the atenolol group. There was a slightly higher incidence of fatal ventricular fibrillation and aortic dissection in the control group, and of bradycardia/asystole in the atenolol group. The data did not indicate any substantial contribution from mechanisms such as limitation of infarct size or prevention of reinfarction or cardiac arrest.


Beta blockade, administered early in the course of myocardial infarction, improves clinical outcome.


1. Lancet 1986; 2 (8498):57-66 Final results
2. Lancet 1988; 1(8591):921-3 Mechanisms of early mortality reduction

Clinical Topics: Arrhythmias and Clinical EP, Implantable Devices, SCD/Ventricular Arrhythmias

Keywords: Myocardial Infarction, Ventricular Fibrillation, Heart Arrest, Bradycardia

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