Evaluating Medical Therapy for Calcific Aortic Stenosis: JACC State-of-the-Art Review.

Despite numerous promising therapeutic targets, there are no proven medical treatments for calcific aortic stenosis (AS). Multiple stakeholders need to come together and several scientific, operational, and trial design challenges must be addressed to capitalize on the recent and emerging mechanistic insights into this prevalent heart valve disease. This review briefly discusses the pathobiology and most promising pharmacologic targets, screening, diagnosis and progression of AS, identification of subgroups that should be targeted in clinical trials, and the need to elicit the patient voice earlier rather than later in clinical trial design and implementation. Potential trial end points and tools for assessment and approaches to implementation and design of clinical trials are reviewed. The efficiencies and advantages offered by a clinical trial network and platform trial approach are highlighted. The objective is to provide practical guidance that will facilitate a series of trials to identify effective medical therapies for AS resulting in expansion of therapeutic options to complement mechanical solutions for late-stage disease.

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Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Funding Support and Author Disclosures Dr Lindman has served on the scientific advisory board for Roche Diagnostics; and has received research grants from Edwards Lifesciences and Roche Diagnostics. Dr Madhavan has received support from an institutional grant by the National Institutes of Health/National Heart, Lung, and Blood Institute to Columbia University Irving Medical Center (grant T32 HL007854). Dr Arsenault has received investigator-initiated research contracts from Pfizer and Ionis Pharmaceuticals; and has served as a consultant for Novartis and Silence Therapeutics. Dr Coylewright has received research grants from Edwards Lifesciences and Boston Scientific; and has served on consulting/advisory boards for Abbott, Medtronic, and Alleviant. Dr Merryman has received support from the National Institutes of Health (grant R35-HL135790) and Fondation Leducq. Dr Harrell has received support from the Clinical and Translational Science Awards (award UL1 TR002243) from the National Center for Advancing Translational Sciences. Dr Mack has served as coprimary investigator for the PARTNER trial for Edwards Lifesciences and the COAPT trial for Abbott; and has served as study chair for the APOLLO trial for Medtronic. Dr Leon has received institutional research support from Edwards Lifesciences, Medtronic, Boston Scientific, and Abbott; and has served on consulting/advisory boards for Medtronic, Boston Scientific, Gore, Meril Lifescience, and Abbott. Dr Pibarot has received research grants from Edwards Lifesciences and Medtronic for echo core lab analyses in transcatheter aortic valve replacement. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.