Overview of completed sudden death trials: European experience

Abstract

Progress in understanding the epidemiology and mechanism of sudden cardiac death (SCD) has been rapid over the past two decades. This, together with the availability of drugs with actions that potentially may counter the pathophysiology of sudden death, has led to myriad trials aimed at prolonging life for high-risk individuals. European countries have contributed a major share both to the development of these drugs and to subsequent tests of their efficacy. Ventricular fibrillation (VF), either unheralded or secondary to fresh myocardial ischemia, is by far the most common cause of SCD. The classes of drugs with profiles that might be expected to influence the occurrence of VF directly are antiarrhythmics, calcium channel blockers, platelet-active agents, and beta-adrenoceptor antagonists. Twenty-four of the European trials that employed agents from these groups have special significance because of their design and size. Studies of two of the calcium channel blockers have not demonstrated any life-saving potential to date. One platelet-active agent - aspirin - has shown favorable trends. Results with the use of antiarrhythmic agents have been disappointing, probably because their adverse effects, including arrhythmogenesis in some patients, have countered the antiarrhythmic effects that other patients have achieved. Nevertheless, evidence suggests that lidocaine can reduce the incidence of VF; this can reasonably be equated with life-saving potential whenever defibrillation is not available. Trials with beta-blocking drugs have been the most encouraging; seven of the 11 trials that have been considered demonstrated a significant reduction in sudden death, which was variously defined, and a strong trend toward reduction was observed with another. None of the trials showed an unfavorable trend. The results of completed trials now offer practical guidance to physicians with responsibility for the care of patients with ischemic heart disease, especially those who have features that indicate high risk.