Evaluation of antiarrhythmic drug efficacy in patients with an ICD: Unlimited potential or replete with complexity and problems?

There are a number of novel ways in which implantable cardioverter defibril lator (ICD) endpoints can be used in clinical trials to evaluate antiarrhyt hmic drugs. The advances in ICD technology (storage, retrieval, and accurat e interpretation of ICD electrograms) expand the potential to include the u se of an ICD endpoint as a clinical surrogate for sudden death. The ICD als o provides the necessary safety net to test new drugs. The frequent need fo r antiarrhythmic drugs in patients already fitted with an ICD (e.g., for at rial fibrillation) necessitates knowledge of the drugs' effect an defibrill ator threshold. There are interpretative problems and challenges associated with all types of ICD trials, A particular difficult issue is the degree t o which the results of data on antiarrhythmic drug efficacy and safety acqu ired in the context of an ICD endpoint trial might be extrapolated to patie nt populations in which the device is not used. These and other challenging issues are discussed, with the goal of enhancing the design and interpreta tion of clinical trials featuring ICD endpoints.