title: Evaluation of antiarrhythmic drug efficacy in patients with an ICD: unlimited potential or replete with complexity and problems?
abstract: There are a number of novel ways in which implantable cardioverter defibrillator (ICD) endpoints can be used in clinical trials to evaluate antiarrhythmic drugs. The advances in ICD technology (storage, retrieval, and accurate interpretation of ICD electrograms) expand the potential to include the use of an ICD endpoint as a clinical surrogate for sudden death. The ICD also provides the necessary safety net to test new drugs. The frequent need for antiarrhythmic drugs in patients already fitted with an ICD (e.g., for atrial fibrillation) necessitates knowledge of the drugs' effect on defibrillator threshold. There are interpretative problems and challenges associated with all types of ICD trials. A particular difficult issue is the degree to which the results of data on antiarrhythmic drug efficacy and safety acquired in the context of an ICD endpoint trial might be extrapolated to patient populations in which the device is not used. These and other challenging issues are discussed, with the goal of enhancing the design and interpretation of clinical trials featuring ICD endpoints.
authors.affiliation: Department of Internal Medicine, Baylor College of Medicine, Houston, Texas 77030, USA. cpratt@bcm.tmc.edu
authors.forename: C M
authors.initials: CM
authors.lastname: Pratt
authors.forename: A J
authors.initials: AJ
authors.lastname: Camm
authors.forename: J T
authors.initials: JT
authors.lastname: Bigger
authors.forename: G
authors.initials: G
authors.lastname: Breithardt
authors.forename: R W
authors.initials: RW
authors.lastname: Campbell
authors.forename: A E
authors.initials: AE
authors.lastname: Epstein
authors.forename: L J
authors.initials: LJ
authors.lastname: Kappenberger
authors.forename: K H
authors.initials: KH
authors.lastname: Kuck
authors.forename: S
authors.initials: S
authors.lastname: Pocock
authors.forename: S
authors.initials: S
authors.lastname: Saksena
authors.forename: A L
authors.initials: AL
authors.lastname: Waldo
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D017147:Defibrillators, Implantable; D004341:Drug Evaluation; D006801:Humans; D012107:Research Design
chemical_list: D000889:Anti-Arrhythmia Agents