THE SEARCH FOR NOVEL ANTIARRHYTHMIC STRATEGIES

The past fifty years of antiarrhythmic drug development have seen Limi ted success in prolonging life and reducing morbidity. It is likely th at arrhythmias are in most instances final common pathways through whi ch changes in the cardiac substrate and in trigger mechanisms are expr essed. We propose that the development and administration of therapies for the arrhythmias themselves, while offering a panacea for a diseas e entity that has evolved and is being overtly manifested, is also an admission of failure to identify and prevent evolution of the substrat e and triggers such that arrhythmias can occur. We suggest that while strategies for treatment and prevention of recurrence of arrhythmias s till warrant exploration, greater hope for the future lies in identify ing means for earlier diagnosis of the arrhythmogenic substrate and tr iggers, and in developing therapies that are ''upstream'' to the arrhy thmia and prevent their initial expression. Means to achieve this end are suggested, using specific arrhythmias as examples. Similarly, to i ncrease the likelihood that clinical studies of new therapies can be s uccessfully concluded and interpreted, we suggest new approaches to pa tient selection, risk stratification, trial endpoints, outcome events and trial methodologies.