This review outlines scientific and operational challenges, potential endpoints, and trial designs to facilitate the development of effective medical therapies for calcific aortic stenosis.
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 in order to capitalize on the recent and emerging mechanistic insights into this prevalent heart valve disease. We briefly discuss the pathobiology and most promising pharmacological targets, screening, diagnosis and progression of AS, identification of sub-groups 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 endpoints 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.
“We are starting to appreciate that CAVS is not simply a passive degenerative process associated with aging but that it involves active mechanisms that may be amenable to intervention. We believe we can improve on the current commonly employed strategy of watchful waiting until patients become eligible for aortic valve replacement.”
Lindman et al. (Mon,) conducted a review in Calcific aortic stenosis. This review outlines scientific and operational challenges, potential endpoints, and trial designs to facilitate the development of effective medical therapies for calcific aortic stenosis.