The modernized classification of cardiac anti-arrhythmic drugs: its application to clinical practice.

Abstract

Cardiac arrhythmias pose a major public health problem and pharmacological intervention remains key to their therapy. The landmark Vaughan Williams (VW, 1970) classification utilizing known actions of then available anti-arrhythmic drugs (AADs) became and remains central to management, but requires revision in response to extensive subsequent advances. Our modernized antiarrhythmic drug (AAD) classification reflected and sought to facilitate such fundamental physiological and clinical development. We here respond to requests for an adaptation of our scheme specifically focussed at clinical practice. This adaptation: (1) improves accessibility of our original scheme to clinical practice, focussing on key AADs in clinical use rather than investigational new drugs (INDs) whilst still conserving and encompassing the classic VW scheme. We nevertheless (2) 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. Additionally, (3) the adopted subclasses within each AAD class parallel clinical practice in including only subclasses containing established AADs, or approved potential off-label drugs, as opposed to those only including INDs. Finally, (4) the simplified scheme remains flexible, permitting drugs to be placed in multiple classes where required, and the future addition of classes and subclasses in the light of future investigations and clinical approvals. We thus derive from our comprehensive modernized AAD classification a more focussed and simpler scheme, for clinical use. This both modernizes but preserves the classic Vaughan Williams classification, and remains flexible accommodating for future developments.