Future evaluation of antiarrhythmic therapy.

The expansion of antiarrhythmic therapy beyond pharmacologic agents to include surgery, devices, and ablation procedures, plus the reaffirmation by the Cardiac Arrhythmia Suppression Trial (CAST) of the need for concurrent placebo-controlled trials to establish a mortality benefit, have resulted in the need to consider the requirements for evaluating therapy. Pharmacologic therapy may be used in three ways: (1) primary; (2) alternative; and (3) adjunctive. To accurately identify a mortality benefit from primary therapy, a placebo-controlled study is necessary. In contrast, control of symptoms may be identified without the same rigorous demands. Current data are limited by the absence of true negative controls for most interventions that claim a possible mortality benefit. Alternative therapy provides a choice between equally effective therapies, neither of which has necessarily been documented to have a mortality benefit. Adjunctive therapy is that which is used for control of symptoms, whereas another therapy is used to provide a presumed or proved mortality benefit. For any of these approaches, therapy must be further evaluated in terms of four modifying variables: (1) impact of therapy on the basis of both its efficacy and efficiency; (2) interpretation of outcome data based on analysis of competing risks; (3) measurement of efficacy in terms of extension of life; and (4) analysis of outcome as the equilibrium between antiarrhythmic benefit and proarrhythmic risk. With these approaches a rational analysis of the effect of therapy and its cost-based benefit can be achieved.