Noninvasive Plaque Imaging to Accelerate Coronary Artery Disease Drug Development

Figtree, Gemma A. and Adamson, Philip D. and Antoniades, Charalambos and Blumenthal, Roger S. and Blaha, Michael and Budoff, Matthew and Celermajer, David S. and Chan, Mark Y. and Chow, Clara K. and Dey, Damini and Dwivedi, Girish and Giannotti, Nicola and Grieve, Stuart M. and Hamilton-Craig, Christian and Kingwell, Bronwyn A. and Kovacic, Jason C. and Min, James K. and Newby, David E. and Patel, Sanjay and Peter, Karlheinz and Psaltis, Peter J. and Vernon, Stephen T. and Wong, Dennis T. and Nicholls, Stephen J. (2022) Noninvasive Plaque Imaging to Accelerate Coronary Artery Disease Drug Development. Circulation, 146 (22). pp.1712-1727. ISSN 0009-7322

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Coronary artery disease (CAD) remains the leading cause of adult mortality globally. Targeting known modifiable risk factors has had substantial benefit, but there remains a need for new approaches. Improvements in invasive and noninvasive imaging techniques have enabled an increasing recognition of distinct quantitative phenotypes of coronary atherosclerosis that are prognostically relevant. There are marked differences in plaque phenotype, from the high-risk, lipid-rich, thin-capped atheroma to the low-risk, quiescent, eccentric, nonobstructive calcified plaque. Such distinct phenotypes reflect different pathophysiologic pathways and are associated with different risks for acute ischemic events. Noninvasive coronary imaging techniques, such as computed tomography, positron emission tomography, and coronary magnetic resonance imaging, have major potential to accelerate cardiovascular drug development, which has been affected by the high costs and protracted timelines of cardiovascular outcome trials. This may be achieved through enrichment of high-risk phenotypes with higher event rates or as primary end points of drug efficacy, at least in phase 2 trials, in a manner historically performed through intravascular coronary imaging studies. Herein, we provide a comprehensive review of the current technology available and its application in clinical trials, including implications for sample size requirements, as well as potential limitations. In its effort to accelerate drug development, the US Food and Drug Administration has approved surrogate end points for 120 conditions, but not for CAD. There are robust data showing the beneficial effects of drugs, including statins, on CAD progression and plaque stabilization in a manner that correlates with established clinical end points of mortality and major adverse cardiovascular events. This, together with a clear mechanistic rationale for using imaging as a surrogate CAD end point, makes it timely for CAD imaging end points to be considered. We discuss the importance of global consensus on these imaging end points and protocols and partnership with regulatory bodies to build a more informed, sustainable staged pathway for novel therapies.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 03 Mar 2023 04:23
Last Modified: 03 Mar 2023 04:23

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