The Cardiac Arrhythmia Suppression Trial - CAST

Description:

Arrhythmia suppression for mortality after myocardial infarction.

Hypothesis:

Suppression of asymptomatic or mildly symptomatic ventricular arrhythmias after acute myocardial infarction with encainide, flecainide, or moricizine, would decrease mortality during long-term follow-up.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 2,309
Mean Follow Up: 10 months (18 months)
Mean Patient Age: 61
Female: 18
Mean Ejection Fraction: 40% (48% of the population had ejection fraction < 40%)

Patient Populations:

Prior myocardial infarction between 6 days and 2 years before screening
Six or more ventricular premature depolarizations per hour noted on ambulatory monitoring
Ejection fraction < 40% for patients whose myocardial infarction had occurred more than 90 days before monitoring.

Exclusions:

Ventricular arrhythmias causing syncope or presyncope
Ventricular tachycardia with 15 or more successive beats at a rate of > 120 beats per minute
Poor patient compliance
Contraindication to antiarrhythmic drug therapy.

Primary Endpoints:

Death from arrhythmia

Secondary Endpoints:

All cause mortality

Drug/Procedures Used:

Encainide
Flecainide
Moricizine

Concomitant Medications:

Beta blocker (32%)
Calcium channel blocker (51%)
Digitalis preparations (20%)
Nitrates (45%)
Diuretic (32%)
Antihypertensives (23%)

Principal Findings:

Encainide and flecainide caused increased cardiovascular mortality with a relative risk of 2.5 (confidence interval 1.7-8.5; p < .001).

These drugs also accounted for a higher total mortality with similar risk ratios.

At 1 year from the time of randomization to blinded therapy, 95% of placebo-treated patients vs 90% of active drug-treated patients remained alive (P = .0006). Similarly, at 1 year, 96% of placebo-treated patients vs 93% of active drug-treated patients remained free of cardiac arrest or arrhythmic death (P = .003).

Interpretation:

Neither Encainide nor Flecainide should be used in the treatment of patients with asymptomatic or minimally symptomatic ventricular arrhythmia after myocardial infarction, even though these drugs may be effective initially in suppressing ventricular arrhythmia. The suppression of asymptomatic or mildly symptomatic ventricular arrhythmias after myocardial infarction does not improve survival and can increase mortality. Treatment strategies designed solely to suppress these arrhythmias should no longer be followed.

References:

1. N Engl J of Med 1989;321:406-12. Design and baseline results
2. JAMA 1993;270(20):2451-5. Final result

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

Keywords: Monitoring, Ambulatory, Risk, Myocardial Infarction, Heart Conduction System, Moricizine, Ventricular Fibrillation, Heart Arrest, Encainide, Tachycardia, Ventricular, Flecainide, Ventricular Premature Complexes


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