A New Therapeutic Framework for Atrial Fibrillation Drug Development
- 19 June 2020
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation Research
- Vol. 127 (1), 184-201
- https://doi.org/10.1161/circresaha.120.316576
Abstract
Atrial fibrillation (AF) is a highly prevalent cardiac arrhythmia and cause of significant morbidity and mortality. Its increasing prevalence in aging societies constitutes a growing challenge to global healthcare systems. Despite substantial unmet needs in AF prevention and treatment, drug developments hitherto have been challenging, and the current pharmaceutical pipeline is nearly empty. In this review, we argue that current drugs for AF are inadequate because of an oversimplified system for patient classification and the development of drugs that do not interdict underlying disease mechanisms. We posit that an improved understanding of AF molecular pathophysiology related to the continuous identification of novel disease-modifying drug targets and an increased appreciation of patient heterogeneity provide a new framework to personalize AF drug development. Together with recent innovations in diagnostics, remote rhythm monitoring, and big data capabilities, we anticipate that adoption of a new framework for patient subsegmentation based on pathophysiological, genetic, and molecular subsets will improve success rates of clinical trials and advance drugs that reduce the individual patient and public health burden of AF.Keywords
This publication has 142 references indexed in Scilit:
- Effect of Sleep Apnea and Continuous Positive Airway Pressure on Cardiac Structure and Recurrence of Atrial FibrillationJournal of the American Heart Association, 2013
- Protein Engineering for Cardiovascular TherapeuticsCirculation Research, 2013
- Molecular basis of selective atrial fibrosis due to overexpression of transforming growth factor-β1Cardiovascular Research, 2013
- Assessment of Left Atrial Deformation and Synchrony by Three-Dimensional Speckle-Tracking Echocardiography: Comparative Studies in Healthy Subjects and Patients with Atrial FibrillationJournal of the American Society of Echocardiography, 2013
- Inflammation in Atrial FibrillationJournal of the American College of Cardiology, 2012
- Intrinsic Cardiac Nerve Activity and Paroxysmal Atrial Tachyarrhythmia in Ambulatory DogsCirculation, 2010
- Endurance sport practice as a risk factor for atrial fibrillation and atrial flutterEP Europace, 2008
- Differential Behaviors of Atrial Versus Ventricular FibroblastsCirculation, 2008
- Potential clinical relevance of the ‘little brain’ on the mammalian heartExperimental Physiology, 2008
- Prediction of the recurrence of atrial fibrillation after cardioversion in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) studyAmerican Heart Journal, 2006