Cardiac Arrhythmia Suppression Trial (CAST)
Condition: Cardiovascular Diseases; Coronary Disease; Death, Sudden, Cardiac; Heart Arrest; Heart Diseases; Myocardial Infarction; Myocardial Ischemia; Ventricular Arrhythmia
MeSH terms: Cardiovascular Diseases; Myocardial Infarction; Arrhythmias, Cardiac; Coronary Disease; Myocardial Ischemia; Heart Arrest; Death, Sudden, Cardiac; Death, Sudden
Study type: Interventional
Phase: Phase 3

Summary: 
      To determine whether drug treatment of asymptomatic ventricular arrhythmias in
      post-myocardial infarction patients reduced the incidence of sudden cardiac death and total
      mortality.
    

Detailed description: 
      BACKGROUND:

      Each year over 400,000 people in the United States die suddenly of coronary heart disease.
      The majority have known coronary heart disease. Of these, the post-myocardial infarction
      population constitutes a large proportion. About 8 to 15 percent of patients who recover from
      an acute myocardial infarction die in the subsequent year. Half of these deaths are usually
      sudden, presumably due to arrhythmia. Advanced age, poor ventricular function, and presence
      of ventricular arrhythmias can identify post-MI patients at high risk of sudden cardiac death
      and all-cause mortality.

      A number of clinical trials have evaluated whether acute or chronic anti-arrhythmic drug
      therapy can reduce mortality in post-MI patients. Of these, only the use of acute intravenous
      and long-term beta-blockers, independently and in combination, had been shown to reduce
      mortality. However, beta-blockers have many actions in addition to being anti-arrhythmic
      agents and it is possible that these other effects may have been particularly important in
      prolonging life.

      None of the clinical trials of other antiarrhythmic drugs had shown significant benefits from
      treatment, and a number had even failed to show a positive trend. It was certainly possible
      that treatment of ventricular premature depolarizations, in itself, did not lead to a
      reduction in mortality, or even sudden death. The studies that had been done, however, had
      not adequately addressed the issue. Most of the studies were small and did not select
      patients on the basis of frequent ectopic beats. Moreover, appropriate drugs in optimal doses
      may not have been used, and adverse effects may well have outweighed any potential benefit.
      Poor compliance, perhaps due to adverse effects, may also have limited the opportunity for a
      beneficial outcome.

      In an effort to address some of these points, the National Heart, Lung, and Blood Institute
      initiated the Cardiac Arrhythmia Pilot Study in 1982. The objectives were to assess: whether
      post-MI patients with documented ventricular arrhythmia could be identified and enrolled into
      a double-blind clinical trial; whether one or more drugs could be found to effectively and
      safely reduce ventricular premature depolarizations over a one-year period; whether
      dose-adjustment could be carried out, using ambulatory ECG's; and whether good patient
      compliance could be maintained. The Cardiac Arrhythmia Pilot Study, which enrolled 500
      patients, evaluated four active drugs (encainide, ethmozine, flecainide, imipramine) against
      placebo. The study was too small to determine whether any of these drugs had an effect on
      mortality or major morbidity. The study was completed in July 1986.

      The pilot study demonstrated that patient recruitment was feasible, that dose-adjustment
      could be accomplished, and that good compliance to the protocol could be achieved. Because of
      the encouraging results of the pilot study, the NHLBI conducted a full-scale trial.

      DESIGN NARRATIVE:

      Randomized, double-blind. Enrollment began in June 1987 when twenty-seven clinical centers
      began to randomize 4,400 post-myocardial infarction patients to placebo or treatment with
      encainide, flecainide, or moricizine. Prior to actual randomization, there was an open-label
      titration period to identify patients who responded to treatment. A total of 1,727 patients
      who responded were randomized: 1,455 to encainide, flecainide, or placebo, and 272 to
      moricizine or placebo. In April 1989, encainide and flecainide were discontinued because of
      increased total mortality and sudden arrhythmic death. CAST continued to compare moricizine
      to placebo in 1,300 patients for 18 months until August 1991 when the moricizine portion of
      the trial was stopped early because of excess deaths. The primary outcome variable in the
      full-scale trial was sudden cardiac death, with total mortality a secondary endpoint. Data
      analysis continued through March 1998.
    

Intervention name(s): encainide; flecainide; moricizine
Intervention type(s): Drug; Drug; Drug
Intervention MeSH terms: Flecainide; Moricizine; Encainide
Allocation: Randomized
Masking: Double
Primary purpose: Prevention