Considerations for Using Atrial Fibrillation Burden as a Surrogate Endpoint A Report from the Cardiovascular Sciences Research Consortium

Atrial fibrillation (AF) care has shifted dramatically, with a focus on early rhythm control to reduce AF-related morbidity and mortality and improve quality of life. However, clinical trials for AF rely on historical definitions of treatment failure, including freedom from recurrence of ≥ 30 seconds of atrial fibrillation/flutter/tachycardia, which is a poor predictor of AF severity, or traditional clinical endpoints (i.e., stroke, heart failure, death) which have low incidence in contemporary AF populations. Therefore, a directly measurable and clinically meaningful measure for these clinical endpoints has the potential to accelerate clinical trials of rhythm control in AF while reducing overall trial overhead. The Cardiovascular Sciences Research Consortium hosted a Think Tank comprising scientists, clinicians, regulators, and industry representatives to develop a roadmap to establish AF burden as a valid surrogate clinical endpoint. This document reviews currently available data to support the use of AF burden as a surrogate endpoint, provides standards for measuring AF burden across measurement modalities and devices, and establishes a practical roadmap for a collaborative approach to validating the use of AF burden. Moving beyond historical definitions of AF treatment success and failure, AF burden has the potential to be a patient-centric endpoint that can leverage contemporary monitoring technologies while serving as an early signifier of AF-related risk.