Clinical Drug Experience Knowledgebase

BACKGROUND:

Survivors of a documented myocardial infarction are recognized as having a high risk of dying relative to the general population. Serious arrhythmias, occurring with or without evidence of new infarction, are a common cause of death in this population. Theoretically, an agent which (1) can block the sympathetic nervous activity thought to be involved in precipitating sudden death and (2) has non-neurogenic antiarrhythmic properties would be of value to people with coronary heart disease. Propranolol, like other beta- blocking agents, has these as well as other properties and therefore might be expected to prevent or retard complications of coronary heart disease such as serious arrhythmias. This would be reflected in a decrease in mortality due to coronary heart disease.

A workshop on chronic antiarrhythmic therapy reviewed contemporary experimental data and clinical practice and recommended that a clinical trial be undertaken to clearly show the effects of beta-blocking drugs on mortality. Subsequently, such a trial was approved by the Clinical Applications and Prevention Advisory Committee, by the Cardiology Advisory Committee, and by the National Heart, Lung, and Blood Advisory Council.

The study protocol was reviewed in February 1978 and recommended for approval by the policy-data monitoring board and ad hoc members. The protocol was approved by the Director of NHLBI in March 1978. Recruitment started on June 19, 1978, and ended in October 1980. A total of 3,837 patients were randomized. Units which participated in the trial included 32 clinical centers, an EKG center, a central laboratory, a coordinating center, a 1-hour ambulatory ECG center, a 24-hour ambulatory EKG center, and an EKG tape quality control center.

DESIGN NARRATIVE:

A randomized, double-blind design with single experimental and control groups. Patients were recruited while in the hospital for an acute myocardial infarction and were enrolled in the study before discharge. Eligible patients fulfilled the study definition of an acute myocardial infarction. The diagnosis was based either on electrocardiographic records showing evolving QRS segment changes or on ST segment and T wave changes together with enzyme changes and appropriate clinical history. One-half of the patients were placed on therapy using a beta-blocking drug (propranolol). The other half received a placebo. The prescribed maintenance dosage of propranolol was either l80 or 240 mgs/day, depending upon serum drug levels. Intervention duration averaged 25 months.

The study completion date listed in this record was obtained from the "Completed Date" entered in the Query View Report System (QVR).