REVIEW article
Front. Cardiovasc. Med.
Sec. Cardiovascular Pharmacology and Drug Discovery
Cardiovascular safety pharmacology: beyond arrhythmic risk assessment
Provisionally accepted
- ERBC group, Baugy, France
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Cardiovascular safety pharmacology arose from the need to assess certain forms of drug induced functional cardiotoxicity in toxicology within a regulatory framework. Cardiotoxic effects resulting from direct or indirect pharmacological effects are difficult to apprehend in conventional toxicology studies, whether electrophysiological and/or hemodynamic. The reflex regulatory systems of the cardiovascular system, and in particular the autonomic nervous system, interfere with and very often minimize the functional impact of these pharmacological effects, which are sometimes only visible over a very short time window. Modeling approaches now make it possible to assess key hemodynamic parameters, going beyond blood pressure alone. Non-clinical cardiovascular safety pharmacology must continue to evolve toward a comprehensive framework for arrhythmic risk, in order to improve its translational relevance to humans and better bridge non-clinical QT prolongation data with clinical risk assessment. It also needs to integrate concepts from clinical research, such as Coumel's triangle, autonomic conflict or hidden cardiotoxicity. The ultimate goal of cardiovascular safety pharmacology should extend beyond protecting participants in clinical trials. It should broaden its scope to include patient subpopulations with underlying cardiovascular disease, who are often the most vulnerable to functional cardiotoxic effects. Twenty-five years after their initial publication, the safety pharmacology guidelines are currently undergoing revision. This review aims to foster a more balanced and comprehensive approach to cardiovascular safety pharmacology, beyond arrhythmic risk
Keywords: Autonomic Nervous System, Cardiac Electrophysiology, cardiovascular pharmacology, drug safety, hemodynamic, Cardiovascular Risk Assessment, safety pharmacology
Received: 07 May 2025; Accepted: 25 Nov 2025.
Copyright: © 2025 FARES and Champéroux. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Raafat FARES
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