Myocardial infarction: arrhythmia: flecainide and encainide increased the risk of death.

Clinical bottom line (level 1b)

  1. Patients with recent myocardial infarction and ventricular premature depolarisations who were given flecainide or encainide, were more likely to die or have a cardiac arrest than those given placebo (NNH = 22 at 10 months) .
  2. Patients given flecainide or encainide were more likely to die from an arrhythmia or have a cardiac arrest (NNH = 30 at 10 months) .
CAST Investigators : New England Journal of Medicine 1989; 321: 406-412
Expires December 2004

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: multicentre, USA and Sweden

1455 patients (aged mean 61 years, 82% male) documented myocardial infarction within 6 days to 2 years, and at least 6 ventricular premature depolarisations per hour (on ambulatory ECG)

Excluded if
  • ventricular arrhythmia causing more severe symptoms (eg. syncope or presyncope) resulting from haemodynamic compromise
  • unsustained ventricular tachycardia with 15 or more successive beats at a rate of 120 or more beats per minute
  • potentially poor compliance
  • contraindications to any of the study drugs
  • other life-threatening conditions
  • ECG abnormalities that would make interpretation of rhythm difficult


    • Control Group: (n = 725, 725 analysed): placebo
    Experimental Group: (n = 730, 730 analysed): encainide 35 mg or 50 mg tds po, or flecainide 100 mg or 150 mg bd po
    Patients first underwent open-label titration phase during which up to three drugs (encainide, flecainide and moricizine) at two oral doses were evaluated. Titration was stopped when arrhythmia was suppressed (>80% reduction of ventricular premature depolarisations and 90% or more reduction of runs of unsustained ventricular tachycardia)
    100% followed for 10 months

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNH
    (95% CI)
    death or cardiac arrest 10 months 22
    (3.03%)    		 56
    (7.7%)    		 -153%
    (-310% to -56%)    		 -4.64%
    (-6.94% to -2.34%)    		 22
    (14 to 43)
    death from arrhythmia or cardiac arrest 10 months 9
    (1.24%)    		 33
    (4.52%)    		 -264%
    (-656% to -76%)    		 -3.28%
    (-4.99% to -1.57%)    		 30
    (20 to 64)

    Comments


    Citation

    1. CAST Investigators , : Special report: Preliminary report: Effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. New England Journal of Medicine 1989; 321: 406-412
    Contributor: Clare Wotton, January 2001
    Reviewer:

    Clinical Question.
    Patient arrhythmia after recent MI
    Intervention or Exposure flecainide or encainide
    Comparison placebo
    Outcome mortality.