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Cardiac Arrest Study Hamburg - CASH
Description:
The Cardiac Arrest Study Hamburg (CASH) trial was designed to compare survival with antiarrhythmic drugs—propafenone, amiodarone, or metoprolol—versus implantable cardioverter defibrillators (ICDs) in survivors of cardiac arrest due to documented ventricular arrhythmias. The trial began in 1987 when ICDs were implanted via thoracotomy, and were still considered investigational devices.
Hypothesis:
ICDs may compare favorably with antiarrhythmic drugs for secondary prevention of life-threatening ventricular arrhythmias.
Study Design
Study Design:
Patients Screened: Not given
Patients Enrolled: 349
NYHA Class: 27% class I, 57% class II, 17% class III
Mean Follow Up: 11 months (propafenone vs. ICD); 57 ± 34 months (amio/metoprolol vs. ICD)
Mean Patient Age: 58 ± 11 years
Female: 20
Mean Ejection Fraction: ICD group: 46 ± 19%
Amiodarone group: 44 ± 17%
metoprolol group: 47 ± 17%
Patient Populations:
Survivors of cardiac arrest caused by documented ventricular tachycardia or ventricular fibrillation
Exclusions:
Acute myocardial infarction, cardiac surgery, electrolyte disturbance, or proarrhythmic drug effect within 72 hours of cardiac arrest
Primary Endpoints:
All-cause mortality
Secondary Endpoints:
Sudden death at two years and recurrent cardiac arrest at two years
Drug/Procedures Used:
Patients were initially randomized in equal numbers to one of four groups: ICD, metoprolol, amiodarone, or propafenone. The propafenone group was terminated early (1992) when interim analysis revealed excess mortality in propafenone compared with ICD patients. Additional patients were then randomized to the three remaining arms. ICDs were epicardial from 1987-1991, and transvenous thereafter.
Concomitant Medications:
Beta-blockers were withheld in the amiodarone, propafenone, and ICD groups.
Principal Findings:
Interim analysis revealed that propafenone treatment (n=56), as compared with ICD (n=59), was associated with increased sudden death (12% vs. 0%, p<0.05) and sudden death or recurrent cardiac arrest (23% vs. 0%, p<0.05), prompting discontinuation of the propafenone arm of the study.
Final results over 57 months' average follow-up reported a trend toward reduced all-cause mortality with ICDs (n=99), compared with the combined amiodarone (n=92) and metoprolol (n=97) groups (36.4% vs. 44.4%, one-tailed p=0.08). ICDs were associated with a reduction in sudden death (13.0% vs. 33.0%, one-sided p=0.005).
Interpretation:
Cardiac arrest survivors treated with the class I-C antiarrhythmic drug propafenone had more frequent serious arrhythmic events than those treated with ICDs. When compared with amiodarone or metoprolol over longer-term follow-up, ICDs significantly reduced sudden death, but not total mortality. At its inception, this was the first randomized trial of ICDs versus pharmacologic therapy for secondary prevention of sudden cardiac death.
Unfortunately, the trial took approximately 10 years to enroll <400 patients, and during this time, enormous changes took place in ICD technology, as well as thinking about antiarrhythmic drugs. The finding of early increased sudden death in the propafenone arm was very important in light of contemporary anti-arrhythmic drug trials. The trend toward reduced all-cause mortality was consistent with the much larger AVID trial, which started later, but was published sooner.
References:
Preliminary results/interim analysis:
Siebels J, Cappato R, Ruppel R, Schneider MA, Kuck KH. ICD versus drugs in cardiac arrest survivors: preliminary results of the Cardiac Arrest Study Hamburg. Pacing Clin Electrophysiol 1993;16:552-8.
Siebels J, Kuck KH. Implantable cardioverter defibrillator compared with antiarrhythmic drug treatment in cardiac arrest survivors (the Cardiac Arrest Study Hamburg). Am Heart J 1994;127:1139-44.
Final results:
Kuck KH, Cappato R, Siebels J, Ruppel R. Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest: the Cardiac Arrest Study Hamburg (CASH). Circulation 2000;102:748-54.
Keywords: Thoracotomy, Tachycardia, Ventricular, Secondary Prevention, Ventricular Fibrillation, Propafenone, Metoprolol, Death, Sudden, Cardiac, Defibrillators, Implantable
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