Cardiac Arrhythmia Suppression

The Cardiac Arrhythmia Suppression Trial (CAST) Investigators, W. Engl J. Med. 321, 406 (1989). 

The Cardiac Arrhythmia Suppression Trial Investigators (1991) Mortality and morbidity in patients receiving encainide, flecainide or placebo. New Engl J Med 324 781... 

Echt DS, Liebson PR, MitcheU B, et al. Mortality and morbidity of patients receiving encain-ide, flecainide or placebo the Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991 324 781-8. 

Mortality In the National Heart, Lung, and Blood Institute s Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multicentered, randomized, double-blind study in patients with asymptomatic nonlife-threatening ventricular arrhythmias who had an Ml more than 6 days but less than 2 years previously, an excessive mortality or nonfatal cardiac arrest rate was seen in patients treated with encainide or flecainide (7.7%) compared with that seen in patients assigned to matched placebo-treated groups (3%). The averaged duration of treatment with encainide or flecainide in this study was 10 months. 

Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. The cardiac arrhythmia suppression trial II investigators. N Engl J Med. Jul 23 1992 327(4) 227-233. 

CAST (1989) Preliminary report effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. The cardiac arrhythmia suppression trial (CAST) investigators. The New En and Journal of Medicine, 321, 406 12. 

The Cardiac Arrhythmia Suppression Trial II Investigators. Effect of the antiarrhythmic agent moricizine on... 

Genetic polymorphism is clinically important e.g. in the CAST (Cardiac Arrhythmia Suppression Trial), serious problems were identified with encainide and flecainide, because of polymorphic metabolism by CYP2D6. 

Question the need for therapy. The mere identification of an abnormality of cardiac rhythm does not necessarily require that the arrhythmia be treated. An excellent justification for conservative treatment was provided by the Cardiac Arrhythmia Suppression Trial (CAST) referred to earlier. 

Flecainide is very effective in suppressing premature ventricular contractions. However, it may cause severe exacerbation of arrhythmia even when normal doses are administered to patients with preexisting ventricular tachyarrhythmias and those with a previous myocardial infarction and ventricular ectopy (see The Cardiac Arrhythmia Suppression Trial). The drug is well absorbed and has a half-life of approximately 20 hours. Elimination is both by hepatic metabolism and by the kidney. The usual dosage of flecainide is 100-200 mg twice a day. 

Premature ventricular contractions (PVCs) are commonly recorded in patients convalescing from myocardial infarction. Since such arrhythmias have been associated with an increased risk of sudden cardiac death, it had been the empiric practice of many physicians to treat PVCs, even if asymp-tomatic, in such patients. In CAST (Cardiac Arrhythmia Suppression Trial [CAST], Echt et al, 1991), an attempt was made to document the efficacy of such therapy in a controlled clinical trial. The effects of several antiarrhythmic drugs on arrhythmia frequency were first evaluated in an open-label fashion. Then, patients in whom antiarrhythmic therapy suppressed PVCs were randomly assigned, in a double-blind fashion, to continue that therapy or its corresponding placebo. 

Echt, D., Liebson, P., Mitchell, L., Peters, R., Obias-Manno, D., Barker, A., Arensberg, D., Baker, A., Friedman, L., Greene, H., Juther, M., and Richardson, D., Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial, New England Journal of Medicine, Vol. 324, No. 12, 1991, pp. 781-788. 

Proarrhythmic effects of antiarrhythmic drugs In the Cardiac Arrhythmia Suppression Trial (CAST) treatment with encainide and flecainide, two class IC antiarrhythmic agents, successfully prevented ventricular ectopic beats in patients who had myocardial infarction. However, continued therapy with either drug was associated with a two- to three-fold increase in death due to cardiac arrhythmias. Similar results were reported for moricizine. Increased death was probably due to drug-induced fatal arrhythmias triggered by recurrent myocardial ischemia. 

Asymptomatic Carotid Atherosclerosis Study Group (1995). Carotid endarterectomy for patients with asymptomatic internal carotid artery stenosis. Journal of the American Medical Association 273 1421-1428 Barnett HJ, Taylor DW, Ehasziw M etal. (1998). The final results of the NASCET trial. New England Journal of Medicine 339 1415-1425 Cardiac Arrhythmia Suppression Trial (CAST) Investigators (1989). Preliminary report effect of encainide and flecainide on mortality in a randomised trial of arrhythmia suppression after myocardial infarction. New England Journal of Medicine 321 406-412 Charleson ME, Horwitz RI (1984). Applying results of randomised trials to clinical practice impact of losses before randomisation. British Medical Journal 289 1281-1284... 

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