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

ReferenceThe 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 -

DesignMulticenter, multinational; initial phase open; main phase randomized, double-blind, placebo-controlled

Patients1725 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 pointMean 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

100Survival(%)

Placebo (n=725)

Encainide or flecainide (n=730)

CAST Investigators. N Engl J Med 1989;321 :406–12.

P=0.000380

CAST: Cardiac Arrhythmia Suppression Trial- RESULTS continued-

Mortality and cardiac arrest

CAST Investigators. N Engl J Med 1989;321:406 –12.

Non-fatal cardiac arrestor 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