Cardiac arrhythmia suppression trial antiarrhythmic drugs

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. 

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. 

Because of the results of the Cardiac Arrhythmia Suppression Trials and other trials, antiarrhythmic drugs (except /3-blockers) should not be used routinely in patients with prior myocardial infarction (Ml) or left ventricular (LV) dysfunction and minor ventricular rhythm disturbances (e.g., premature ventricular complexs). 

AVID Antiarrhythmic drug Versus Internal Defibrillator trial CAST Cardiac Arrhythmia Suppression Trial DCC direct-current cardioversion EADs early after-depolarizations... 

Prophylactic antiarrhythmic drug use does not improve total survival. The Cardiac Arrhythmia Suppression Trial (CAST) (125), based on the supposition that frequent PVCs after myocardial infarction are associated with increased risk of sudden death, evaluated the long-term benefits of antiarrhythmic drug therapy for those patients with > lOPVCs/h after myocardial infarction. After PVC suppression was shown to occur on the antiarrhythmic drug, patients were randomized to the antiarrhythmic drug showing apparent benefit (Class... 

Flecainide slows conduction in all cardiac cells including the anomalous pathways responsible for the Wolff-Parkinson-White (WPW) syndrome. Together with encainide and moricizine, it underwent clinical trials to establish if suppression of asymptomatic premature beats with antiarrhythmic drugs would reduce the risk of death from arrhythmia after myocardial infarction. The study was terminated after preliminary analysis of 1727 patients revealed that mortality in the groups treated with flecainide or encainide was 7.7% compared with 3.0% in controls. The most likely explanation for the result was the induction of lethal ventricular arrhythmias possibly due to ischaemia by flecainide and encainide, i.e. a proarrhythmic effect. In the light of these findings the indications for flecainide are restricted to patients with no evidence of structural heart disease. The most common indication, indeed where it is the drug of choice, is atrioventricular re-entrant tachycardia, such as AV nodal tachycardia or in the tachycardias associated with the WPW syndrome or similar conditions with anomalous pathways. This should be as a prelude to definitive treatment with radiofrequency ablation. Flecainide may also be useful in patients with paroxysmal atrial fibrillation. 

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