Myocardial infarction: arrhythmias: encainide and flecainide increased the risk of dying.

Clinical bottom line (level 1b)

  1. Patients with a recent myocardial infarction, a poor ejection fraction and asymptomatic or mildly symptomatic ventricular arrhythmias who received encainide or flecainide compared with placebo were more likely to die (NNH = 21 at 10 months) , particularly from arrhythmias (NNH = 28 at 10 months) .
Echt et al: New England Journal of Medicine 1991; 324 (12): 781-788
Expires December 2004

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: 27 acute hospitals, North America and Sweden

1498 patients (aged mean 61 years, 82% male) with myocardial infarction and 6 or more premature ventricular contractions per hour (on ambulatory ECG) who responded to flecainide, encainide or moricizine (80% or more suppression of PVC, 90% or more suppression of runs of VT within 15 days)

Excluded if
  • < 6 days or > 2 years after MI
  • ventricular tachycardia of 15 or more beats at a rate of 120 or more beats/min
  • symptoms more severe than palpitations resulting from haemodynamic compromise (e.g. syncope or presyncope)
  • ejection fraction > 55% within 90 days of MI
  • ejection fraction > 40% >90 days after MI
  • potentially poor compliance
  • contraindications to any of the study drugs
  • other life-threatening abnormalities
  • ECG abnormalities that made interpretation of rhythm difficult
  • arrhythmia increased during titration period


    • Control Group: (n = 743, 743 analysed): placebo
    Experimental Group: (n = 755, 755 analysed): flecainide 100 mg or 150 mg bd po, or encainide 35 mg or 50 mg tds po
    Patients with ejection fractions 30% or less were not randomised to flecainide.
    100% followed for 10 months
    Outcome notes:
    • death or cardiac arrest due to arrhythmia : defined as: witnessed and instantaneous without new or accelerating symptoms; witness and preceded by symptoms attributable to myocardial ischemia (without shock or class IV heart failure); witness and preceded by symptoms attributable to cardiac arrhythmias (syncope or near-syncope); unwitnessed but without evidence of another cause

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNH
    (95% CI)
    death or cardiac arrest 10 months 26
    (3.50%)    		 63
    (8.34%)    		 -138%
    (-272% to -53%)    		 -4.85%
    (-7.22% to -2.47%)    		 21
    (14 to 40)
    death or cardiac arrest due to arrhythmia 10 months 16
    (2.15%)    		 43
    (5.70%)    		 -164%
    (-365% to -50%)    		 -3.54%
    (-5.50% to -1.59%)    		 28
    (18 to 63)

  • Non-fatal proarrhythmias were not clearly commoner in patients on flecainide or encainide.
  • Compliance (pill count) was > 90% for 70% of patients.

    • Comments

    1. Concomitant drug therapy was similar in both groups.
    2. Follow-on from CAST preliminary report in 1989 (NEJM 1989: 321: 406-412).

    Citation

    1. Echt DS, Liebson PR, Mitchell B, et al: Mortality and morbidity of patients receiving encainide, flecainide, or placebo: the Cardiac Arrhythmia Suppression Trial. New England Journal of Medicine 1991; 324 (12): 781-788
    Contributor: Nick Shenker and Chris Ball, December 2000
    Reviewer:

    Clinical Question.
    Patient MI
    Intervention or Exposure encainide or flecainide
    Comparison placebo
    Outcome death or cardiac arrest