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Events in the Cardiac Arrhythmia Suppression Trial (CAST): mortality in the entire population enrolled
A E Epstein1, J T Bigger, D G Wyse
1Department of Medicine, University of Alabama, Birmingham.
Insights
Antiarrhythmic drugs like encainide and flecainide did not improve survival in post-myocardial infarction patients with ventricular arrhythmias. The Cardiac Arrhythmia Suppression Trial (CAST) found lower survival rates in patients treated with these drugs compared to placebo.
Area of Science:
- Cardiology
- Clinical Trials
- Pharmacology
Background:
- Ventricular arrhythmias post-myocardial infarction (MI) are associated with increased mortality.
- Antiarrhythmic drugs are often used to suppress these arrhythmias.
- The Cardiac Arrhythmia Suppression Trial (CAST) investigated the efficacy of such suppression on survival.
Purpose of the Study:
- To test the hypothesis that suppressing ventricular arrhythmias with antiarrhythmic drugs after MI improves survival.
- To evaluate the survival outcomes of patients treated with encainide or flecainide versus placebo.
Main Methods:
- Initiated the Cardiac Arrhythmia Suppression Trial (CAST) with a prerandomization, open-label titration period.
- Randomized patients with suppressed or partially suppressed arrhythmias to double-blind, placebo-controlled therapy.
- Monitored overall survival and survival free of arrhythmic death or cardiac arrest.
Main Results:
- Overall survival and survival free of arrhythmic death or cardiac arrest were lower in patients treated with encainide or flecainide compared to placebo.
- The 1-year mortality estimate for all enrolled CAST patients was 10.3%.
- The death rate in patients randomized to placebo was lower than anticipated.
Conclusions:
- Suppression of ventricular arrhythmias with encainide or flecainide after MI did not improve survival and may be associated with increased mortality.
- The findings challenge the conventional approach of routine arrhythmia suppression post-MI.
- Further investigation into the "natural" mortality rate in these patients is warranted.
Abstract:
To test the hypothesis that suppression of ventricular arrhythmias by antiarrhythmic drugs after myocardial infarction improves survival, the Cardiac Arrhythmia Suppression Trial (CAST) was initiated. Suppression was evaluated before randomization during an open label titration period. Patients whose arrhythmias were suppressed were randomized in the main study and those whose arrhythmias were partially suppressed were randomized in a substudy. Overall survival and survival free of arrhythmic death or cardiac arrest were lower [corrected] in patients treated with encainide or flecainide than in patients treated with placebo. However, the death rate in patients randomized to placebo therapy was lower than expected. This report describes the survival experience of all patients enrolled in CAST and compares it with mortality in other studies of patients with ventricular arrhythmias after myocardial infarction. As of April 18, 1989, 2,371 patients had enrolled in CAST and entered prerandomization, open label titration: 1,913 (81%) were randomized to double-blind, placebo-controlled therapy (1,775 patients whose arrhythmias were suppressed and 138 patients whose arrhythmias were partially suppressed during open label titration); and 458 patients (19%) were not randomized because they were still in titration, had died during titration or had withdrawn. Including all patients who enrolled in CAST, the actuarial (Kaplan-Meier) estimate of 1-year mortality was 10.3%. To estimate the "natural" mortality rate of patients enrolled in CAST, an analysis was done that adjusted for deaths that might be attributable to encainide or flecainide treatment either during prerandomization, open label drug titration or after randomization. Because the censoring procedure excluded patients treated with encainide or flecainide after randomization, the mortality estimate will be less than the unadjusted mortality estimate of 10.3%.(ABSTRACT TRUNCATED AT 250 WORDS)