The CAST trial: Anti-arrhythmic agents increase risk of death in patients after MI [Classics Series]

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1. The use of class IC anti-arrhythmic agents flecainide and encainide in patients following myocardial infarction with left ventricular dysfunction increases the risk of death due to arrhythmia and shock.

Study Rundown: Venticular arrhythmia is a major cause of cardiac death following myocardial infarction. Thus, the CAST study sought to determine whether suppression of ventricular ectopy with class IC anti-arrhythmic drugs in patients with a recent myocardial infarction would improve outcomes, including mortality. Unfortunately, the results demonstrated increased risk of death from arrhythmia and any cause in those patients receiving these drugs following myocardial infarction. Interestingly, in this study, this increased incidence of arrhythmia-associated death was not matched correspondingly with an increased incidence of non-lethal events involving arrhythmia. This study was one of the first to encourage practicing caution in the use of anti-arrhythmic drugs in patients with cardiovascular disease, including following acute myocardial infarction.

In sum, the use of class IC antiarrhymic agents flecainide and encainide for suppression of ventricular ectopy should be avoided in patients post-myocardial infarction, as they carry excess risk of mortality.

Please click to read study in NEJM

In Depth [randomized, controlled study]: Originally published in NEJM in 1991, this trial enrolled a total of 1,498 patients. Patients with a recent myocardial infarction, ventricular dysfunction, and asymptomatic or mildly symptomatic ventricular arrhythmia were eligible for this study. The study employed an initial open-label titritation period to identify patients who responded to at least one of the drugs with 80-90% suppression of ventricular arrhythmia. The patients were then randomized to receive either study drug or placebo. The primary end-point was death or cardiac arrest with resuscitation, either of which occurring secondary to arrhythmia.

The trial was originally planned to last three years, but was discontinued one year early due to results suggesting excess death in the treatment arm. Findings demonstrated that death from arrhythmia was significantly increased in the treatment group receiving flecainide or encainide as compared to those receiving placebo (RR 2.64; 95% CI 1.60-4.36). Mortality from any cause was also significantly more likely in the treatment arms (RR 2.38; 95% CI 1.59-3.57).

By Aimee Li, M.D.; Andrew Cheung, M.D.

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