An Overview of Drug-Induced Sodium Channel Blockade and Changes in Cardiac Conduction: Implications for Drug Safety

The HESI Cardiac Safety Committee, alongside academic and industry collaborators, has published a new review article titled “An Overview of Drug-Induced Sodium Channel Blockade and Changes in Cardiac Conduction: Implications for Drug Safety” in Clinical and Translational Science. This publication addresses the critical role of sodium channel Nav1.5 in cardiac safety assessments and provides guidance for identifying and mitigating proarrhythmic risks in drug development.

Key Takeaways:

1. Understanding Nav1.5 Blockade: Drug-induced blockade of cardiac sodium channel Nav1.5 can slow cardiac conduction, increase QRS duration, and heighten proarrhythmic risks.

2. Clinical and Regulatory Gaps: Despite its importance, there is no standardized framework for assessing conduction slowing compared to QT prolongation.

3. Methodological Advances: The review outlines in silico, in vitro, and in vivo tools for evaluating Nav1.5 block, emphasizing a “weight of evidence” approach.

4. Translational Challenges: The article highlights species-specific differences and challenges in translating nonclinical findings to clinical outcomes.

5. Risk Mitigation Strategies: Early screening and robust biophysical characterization can improve cardiac safety predictions during drug development.

Why It Matters: This article bridges gaps in cardiac safety assessments, offering actionable insights to researchers, regulators, and drug developers. Understanding Nav1.5 pharmacology is critical for identifying and managing potential safety concerns in both cardiac and non-cardiac drugs.

Who Should Read This: Drug developers, safety pharmacologists, regulatory scientists, and anyone involved in cardiac safety assessments will benefit from this comprehensive overview.

Read the full article here: https://doi.org/10.1111/cts.70098