14th International Congress
THE "NEW FRONTIERS"
OF ARRHYTHMIAS 2000

Jan. 29 - Feb. 5, 2000
Marilleva, Trento, Italy

RT-144

An update on clinical trials for the primary prevention of sudden cardiac death

Adam Zivin, Gust H. Bardy.
University of Washington Medical Center, Seattle, USA

Introduction

Recently completed trials have begun to address the issue of whether implantable defibrillators (ICDs) or antiarrhythmic drugs, in particular amiodarone, prolong life in patients with documented malignant ventricular arrhythmias^1-3. The data from these trials, while not placebo-controlled, suggest that the risk of sudden death in this population may justify the use of a therapy that is known to quickly terminate malignant ventricular arrhythmias. On the other hand, in patients without such a history, and only a statistically higher risk of malignant arrhythmias, the question of whether treatment with an ICD or an antiarrhythmic drug will prolong life remains unresolved. With the assumption that device or pharmacologic antiarrhythmic therapy is expected to reduce deaths from arrhythmia only, effective primary prevention targeting arrhythmic death depends, ideally, on proving that potentially reversible tachyarrhythmias are the dominant mechanism of death. For the large scale trials needed to prove mortality benefit even in relatively high risk patients, determining the mode of death is problematic⁴. For practical reasons, “sudden death” – variously defined – has been used in most studies as a surrogate for “arrhythmic death”. Given the myriad potential causes of even precipitous hemodynamic collapse in those with heart disease, this is not a valid assumption^5-8. In primary prevention, reduction of total mortality is the most meaningful endpoint and is the only reliable endpoint not subject to categorization bias in intention-to-treat analysis (Tab. I).

TABLE I – Potential sources of bias in mortality trials

Key Words