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Evevident
Original paper
1989NEJMCardiology

CAST

Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction

RCTArrhythmia after myocardial infarction

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Overview

Suppressing post-MI ventricular ectopy with class IC drugs increased mortality.

Clinical takeaway

CAST is the canonical surrogate-outcome cautionary tale: drugs that suppressed ventricular ectopy after MI caused excess arrhythmic death and cardiac arrest.

Key result

Encainide/flecainide increased arrhythmic death or cardiac arrest versus placebo.

Practice impact

Ended routine class IC antiarrhythmic suppression of asymptomatic ventricular ectopy after MI.

Evidence

Study design

Randomized, double-blind, placebo-controlled trial stopped early for harm.

Enrollment

1,498

Follow-up

Mean about 10 months at preliminary report.

Geography

United States

Clinical question

Does suppressing asymptomatic or mildly symptomatic ventricular ectopy after MI with class IC antiarrhythmics improve survival?

Population

  • Post-myocardial infarction patients with frequent or complex ventricular premature depolarizations that could be suppressed during open-label titration.

Intervention

Encainide or flecainide.

Comparator

Placebo.

Primary outcome

Arrhythmic death or nonfatal cardiac arrest.

Class IC antiarrhythmic therapy increased arrhythmic death or cardiac arrest despite suppressing ventricular ectopy.

Relative risk / 3.6 / CI approximate excess risk reported in preliminary CAST / p=significant

Key results

  • Arrhythmic death or cardiac arrest was higher with encainide/flecainide than placebo.
  • Total mortality was also higher with active therapy.
  • The trial was stopped early for excess mortality.

Harms

  • Excess arrhythmic death and nonfatal cardiac arrest.
  • Excess total mortality.

Clinical Use

When to cite

  • When warning against treating surrogate endpoints without outcome evidence.
  • When explaining why flecainide/propafenone are avoided in structural heart disease.

Practice impact

  • Changed arrhythmia management by prioritizing patient-centered outcomes over suppression of ventricular ectopy.
  • Contraindicated class IC agents in many patients with structural heart disease or prior MI.

Applicability

  • Most relevant to post-MI or structural-heart-disease patients with ventricular ectopy.

Limitations

  • Studied older post-MI care before contemporary reperfusion, ICD, and heart-failure therapy.
  • Does not prohibit class IC drugs in carefully selected patients without structural heart disease.

Common misinterpretations

  • The lesson is not that all antiarrhythmics are harmful; the lesson is that surrogate rhythm suppression can worsen survival.

Related evidence

AFFIRM - ContextSCD-HeFT - Later Trial

Citation

Cardiac Arrhythmia Suppression Trial (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(6):406-412. doi:10.1056/NEJM198908103210629

Neither encainide nor flecainide should be used in the treatment of patients with asymptomatic or mildly symptomatic ventricular arrhythmia after myocardial infarction.