Are there alternatives to mortality as an endpoint in clinical trials of atrial fibrillation?
Although atrial fibrillation (AF) is associated with an increased risk of death in many cohort studies and, therefore, is an endpoint of interest in trials of management of AF, the frequency of occurrence is low. Arrhythmia suppression as a surrogate endpoint for mortality in trials of rhythm management has a bad reputation. Recently, rehospitalization has been suggested as a possible surrogate for mortality in patients with potentially lethal ventricular arrhythmias. The prospect of alternatives to mortality in studies of patients with AF has been explored in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial. That analysis suggested that hospitalization for cardiovascular reasons (CV hospitalization) in patients such as those enrolled in AFFIRM may have many characteristics of a good surrogate for mortality. Furthermore, modeling based on the AFFIRM research plan and using CV hospitalization in a composite endpoint with death from all causes as an alternative to death alone provides ample power to detect even modest differences (>/=15%) with substantial reduction of the number of subjects that need to be enrolled. However, there are limitations in the AFFIRM data on these points. More research is needed to define suitable alternatives to death as an endpoint for trials in a broad spectrum of patients with AF.
Wyse
D George
DG
Department of Cardiac Sciences and Libin Cardiovascular Institute of Alberta, University of Calgary, G009 Health Sciences Center, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1. dgwyse@ucalgary.ca
D001281:Atrial Fibrillation / Q000401:mortality*; D016009:Chi-Square Distribution; D002986:Clinical Trials as Topic; D023381:Endpoint Determination; D006801:Humans; D016016:Proportional Hazards Models