Download CAST: Cardiac Arrhythmia Suppression Trial

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 continuedAll-cause mortality
Survival
(%)
100
95
90
85
Placebo (n=725)
Encainide or flecainide (n=730)
P=0.0003
80
0
50 100 150 200 250 300 350 400 450 500
Days after randomization
CAST Investigators. N Engl J Med 1989;321:406–12.
CAST: Cardiac Arrhythmia Suppression Trial
- RESULTS continuedMortality and cardiac arrest
Placebo
(n=725)
No. (%)
Encainide/flecainide
(n=730)
No. (%)
Relative risk
(95% CI)
Non-fatal cardiac arrest
or death from arrhythmia
9 (1.2)
33 (4.5)
3.6 (1.7–8.5)
Other cardiac death
6 (0.8)
14 (1.9)
–
Non-cardiac or unclassified death
or cardiac arrest
7 (1.0)
9 (1.2)
–
22 (3.0)
56 (7.7)
2.5 (1.6–4.5)
300
293
Total death or cardiac arrest
Average days of exposure
CAST Investigators. N Engl J Med 1989;321:406–12.
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