TY - JOUR
T1 - The cardiac arrhythmia suppression trial
T2 - Background, interim results and implications
AU - Pratt, Craig M.
AU - Moye, Lemuel A.
PY - 1990/1/16
Y1 - 1990/1/16
N2 - The Cardiac Arrhythmia Suppression Trial (CAST) was designed to test the hypothesis that suppression of ventricular premature complexes (VPCs) in survivors of acute myocardial infarction would reduce arrhythmic death risk. Instead, a preliminary finding from the CAST was that the encainide and flecainide groups had a 3.6-fold increase in arrhythmic death compared with their placebo group. These unfortunate results were especially surprising in that the CAST population represented patients in whom the risk of arrhythmic death was only moderate and the risk of proarrhythmia was thought to be low. In contrast, the arrhythmic death rate of the CAST placebo group was unusually low, to the extent that it paralleled the arrhythmic death rate in previous clinical trials of patients surviving myocardial infarction with no ventricular arrhythmia. The excessive arrhythmic death rate in patients taking encainide and flecainide occurred over the duration of the CAST, implying a proarrhythmic effect that may be due to mechanisms that are unique in this population, and thus challenging traditional concepts of proarrhythmia. The existing knowledge regarding the proarrhythmic and negative inotropic effects of encainide and flecainide are reviewed. The previous pharmaceutical database experience with these 2 antiarrhythmic drugs exceeded 3,000 patients; however, there was no indication of this serious proarrhythmic effect. In contrast, the CAST population taking encainide and flecainide totaled only 725 patients who were followed for 10 months and had an extremely high proarrhythmic event rate. The reasons for this discrepancy are discussed. The results of the CAST emphasize the power of a randomized, placebo-controlled clinical trial to uncover previously unsuspected benefits or liabilities of traditional therapies.
AB - The Cardiac Arrhythmia Suppression Trial (CAST) was designed to test the hypothesis that suppression of ventricular premature complexes (VPCs) in survivors of acute myocardial infarction would reduce arrhythmic death risk. Instead, a preliminary finding from the CAST was that the encainide and flecainide groups had a 3.6-fold increase in arrhythmic death compared with their placebo group. These unfortunate results were especially surprising in that the CAST population represented patients in whom the risk of arrhythmic death was only moderate and the risk of proarrhythmia was thought to be low. In contrast, the arrhythmic death rate of the CAST placebo group was unusually low, to the extent that it paralleled the arrhythmic death rate in previous clinical trials of patients surviving myocardial infarction with no ventricular arrhythmia. The excessive arrhythmic death rate in patients taking encainide and flecainide occurred over the duration of the CAST, implying a proarrhythmic effect that may be due to mechanisms that are unique in this population, and thus challenging traditional concepts of proarrhythmia. The existing knowledge regarding the proarrhythmic and negative inotropic effects of encainide and flecainide are reviewed. The previous pharmaceutical database experience with these 2 antiarrhythmic drugs exceeded 3,000 patients; however, there was no indication of this serious proarrhythmic effect. In contrast, the CAST population taking encainide and flecainide totaled only 725 patients who were followed for 10 months and had an extremely high proarrhythmic event rate. The reasons for this discrepancy are discussed. The results of the CAST emphasize the power of a randomized, placebo-controlled clinical trial to uncover previously unsuspected benefits or liabilities of traditional therapies.
UR - http://www.scopus.com/inward/record.url?scp=0025022540&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025022540&partnerID=8YFLogxK
U2 - 10.1016/0002-9149(90)91287-G
DO - 10.1016/0002-9149(90)91287-G
M3 - Article
C2 - 2105049
AN - SCOPUS:0025022540
SN - 0002-9149
VL - 65
SP - 20
EP - 29
JO - The American Journal of Cardiology
JF - The American Journal of Cardiology
IS - 4
ER -