Methodology for clinical trials with antiarrhythmic drugs to prevent cardiac death: US experience.

Sudden cardiac death is a massive public health problem that claims almost a half million lives a year in the United States. Several high-risk groups have been identified: survivors of cardiac arrest; patients with recurrent sustained ventricular tachycardia; survivors of myocardial infarction (MI) who have more than 10 ventricular premature depolarizations (VPD) per hour or repetitive VPD; and patients with class III or IV congestive heart failure (CHF) and unsustained ventricular tachycardia. The effects of open label drug treatment have been tested in survivors of cardiac arrest or sustained ventricular tachycardia using either electrophysiologic studies or 24-hour ECG recordings and exercise testing. Patients classified as drug responders using these methods have a lower mortality rate during follow-up than do those classified as nonresponders. This result is difficult to interpret. The test procedures may be identifying effective drugs, or alternatively, drug testing may identify high- and low-risk groups even though the drugs have no effect on survival. Recently, study designs have been proposed for conducting controlled trials in patients with malignant arrhythmias. Ventricular arrhythmias after MI have been the subject of intensive study for the past 20 years. About 20% of these patients have ventricular arrhythmias between 6 and 90 days after MI. The presence of ventricular arrhythmias after MI increases the risk of dying two- to fourfold. Arrhythmias predict death independently of left ventricular dysfunction. However, it has not been demonstrated that treatment of ventricular arrhythmias after MI significantly decreases mortality. The goals of the Cardiac Arrhythmia Pilot Study (CAPS) were: to find a therapeutic strategy that could significantly suppress ventricular arrhythmias with an acceptable adverse effect rate; to determine efficient methods for case finding; to identify efficient methods for evaluating the efficacy of antiarrhythmic drug therapy; to demonstrate the feasibility of recruiting patients and maintaining treatment over a 1-year period; and to evaluate the feasibility and usefulness of behavioral studies. The study enrolled 502 patients, randomizing approximately 100 patients each into one of five treatment limbs: one group treated with placebo, and four treated with antiarrhythmic drugs (two with class IC and two with class IA action). Dose adjustment was permitted; patients who failed to satisfy the criteria for drug efficacy were permitted to cross over to a second drug (patients on class IC agents crossed over to class IA agents and vice versa).(ABSTRACT TRUNCATED AT 400 WORDS)

RCT Entities:   Population Interventions Outcomes