CAST: Cardiac Arrhythmia Suppression Trial
Purpose
To determine whether therapy with class Ic antiarrhythmics to suppress asymptomatic or mildly symptomatic ventricular arrhythmias after MI reduces mortality due to arrhythmia
Reference
The CAST Investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med 1989;321:406–12.
CAST: Cardiac Arrhythmia Suppression Trial - TRIAL DESIGN -
Design
Multicenter, multinational; initial phase open; main phase randomized, double-blind, placebo-controlled
Patients
1725 patients with >6 ventricular premature depolarizations/h (24h Holter recording) and left ventricular ejection fraction <0.55 at <90 days after MI or <0.40 at >90 days after MI
Follow up and primary end point
Mean 10 months follow up. Primary endpoint death from arrhythmia
Treatment
Open titration phase (mean 15 days) to select patients in whom drug (encainide, flecainide or moricizine) suppressed arrhythmias
Selected patients then randomized to three-times daily placebo, encainide 35–50 mg, flecainide 100 mg or moricizine 200–250 mg (results for moricizine not reported here)
CAST: Cardiac Arrhythmia Suppression Trial - RESULTS -
Study of encainide/flecainide vs. placebo halted at mean follow up of 10 months on recommendation of CAST Data and Safety Monitoring Board because in group taking encainide or flecainide, compared with placebo group:
All-cause mortality significantly higher
Non-fatal cardiac arrest or death from arrhythmia significantly higher
Death from other cardiac causes also higher
Results consistent across all subgroups examined
No confounding factors were identified to explain marked differences between encainide/flecainide and placebo
Study subsequently modified to continue with moricizine (CAST II)
CAST: Cardiac Arrhythmia Suppression Trial - RESULTS continued-
All-cause mortality
Days after randomization
0
50
100
150
200
250
300
350
400
450
500
85
90
95
100
Survival
(%)
Placebo (n=725)
Encainide or flecainide (n=730)
CAST Investigators.
N Engl J Med
1989;
321
:406
–
12.
P=0.0003
80
CAST: Cardiac Arrhythmia Suppression Trial - RESULTS continued-
Mortality and cardiac arrest
CAST Investigators.
N Engl J Med
1989;
321
:406
–
12.
Non-fatal cardiac arrest
or death from arrhythmia
Other cardiac death
Non-cardiac or unclassified death
or cardiac arrest
Total death or cardiac arrest
Average days of exposure
9 (1.2)
6 (0.8)
7 (1.0)
22 (3.0)
300
33 (4.5)
14 (1.9)
9 (1.2)
56 (7.7)
293
3.6 (1.7
–
8.5)
–
–
2.5 (1.6
–
4.5)
Placebo
(n=725)
No. (%)
Encainide/flecainide
(n=730)
No. (%)
Relative risk
(95% CI)
CAST: Cardiac Arrhythmia Suppression Trial - SUMMARY -
In patients with asymptomatic or mildly symptomatic ventricular arrhythmias after MI, encainide or flecainide started at mean of 15 days after MI caused:
Excessive mortality risk
Excessive risk of death from arrhythmia