The modernized classification of cardiac antiarrhythmic drugs: Its application to clinical practice

Abstract

Cardiac arrhythmias pose a major public health problem, and pharmacologic intervention remains key to their therapy. The 1970 landmark Vaughan Williams (VW) classification utilizing known actions of then available antiarrhythmic drugs (AADs) became and remains central to management, but it requires revision in response to extensive subsequent advances. Our modernized AAD classification reflected and sought to facilitate such fundamental physiological and clinical development. Here we respond to requests for an adaptation of our scheme specifically focused on clinical practice. (1) This adaptation improves the accessibility of our original scheme to clinical practice, focusing on key AADs in clinical use rather than investigational new drugs (INDs) while conserving and encompassing the classic VW scheme. (2) We preserve a rational conceptual framework based on current understanding of the relevant electrophysiological events, their underlying cellular or molecular cardiomyocyte targets, and the functional mechanisms they mediate. (3) The adopted subclasses within each AAD class parallel clinical practice by including only subclasses containing established AADs, or approved potential off-label drugs, as opposed to those only including INDs. (4) The simplified scheme remains flexible, permitting drugs to be placed in multiple classes where required, and the addition of classes and subclasses in light of future investigations and clinical approvals. Thus, we derive from our comprehensive modernized AAD classification a more focused and simpler scheme for clinical use. This both modernizes yet preserves the classic VW classification and remains flexible, thus accommodating future developments.

Keywords: Antiarrhythmic drugs; Ca(2+) homeostasis; Cardiac arrhythmias; Ion channels; Miles Vaughan Williams.